1
Q
Location of Major Endocrine Organs
A
Major endocrine glands:
- Pituitary
- Pineal
- Thyroid/Parathyroid
- Adrenal
Organs containing endocrine cells: hypothalamus, skin,Thymus, Heart, liver, stomach, Small intestine, pancreas, kidney, ovary, testes, adipocytes
2
Q
- Second messenger system of the body
- Uses chemical messages (hormones) that are released into the blood
- Hormones control several major processes
- Reproduction
- Growth and development
- Mobilization of body defenses
- Maintenance of much of homeostasis
- Regulation of metabolism
A
Endocrine System
3
Q
- are produced by specialized cells
- Cells secrete __ into extracellular fluids
- Blood transfers __ to target sites
- regulate the activity of other cells
A
Hormones
4
Q
4 Main Groups of Chemicals that Act as Hormone
A
- Protein/Glycoprotein - insulin, growth hormone, PTH
- Small Peptide Molecules - Vasopressin and products of enteroendocrine cells
- Amino Acid Derivatives - thyroxine, epinephrine and norepinephrine
- Steroid - derived from cholesterol like adrenal cortical hormone, ovarian and testicular hormones
5
Q
Control of Hormone Release
A
- Hormone levels in the blood are maintained by negative feedback
- A stimulus or low hormone levels in the blood triggers the release of more hormone
- Hormone release stops once an appropriate level in the blood is reached
6
Q
Endocrine glands are activated by other hormones
A
Hormonal Stimuli of Endocrine Glands
7
Q
Changing blood levels of certain ions stimulate hormone release
A
Humoral Stimuli of Endocrine Glands
8
Q
- Nerve impulses stimulate hormone release
- Most are under control of the sympathetic nervous system
A
Neural Stimuli of Endocrine Glands
9
Q
Characteristics of Endocrine Glands
A
- The glands are ductless; thus, hormonal secretions are poured directly to the blood through the capillaries.
- The internal supporting framework is reticular tissue.
- Highly vascular, thus provided with rich capillary networks among and between groups of secretory cells.
- The capillaries are fenestrated type in which endothelial wall contains numerous pores or openings which are covered by very thin diaphragms.
10
Q
Development of the Endocrine System
A
On the basis of their germ layer of origin, the endocrine glands may either be ectodermal, mesodermal or endodermal.
- Ectodermal in origin - Pituitary gland; Pineal gland; Adrenal medulla
- Mesodermal in origin - Adrenal cortex; Leydig cells of the testis; Theca interna cells of the ovary
- Endodermal in origin - Thyroid gland; Parathyroid gland; Islets of Langerhans; Parafollicular cells or C-cells
11
Q
Development of the Pituitary Gland
A
This develops from two sources:
- Rathke’s pouch
- Ectodermal outpocketing of the stomodeum (future mouth)
- Gives rise to the ADENOHYPOPHYSIS - Infundibulum
- Downward extension of the diencephalon
- Gives rise to the NEUROHYPOPHYSIS
12
Q
- Anterior wall of Rathke’s pouch gives rise to the Pars distalis and the Pars tubercles
- Posterior wall of Rathke’s pouch gives rise to the Pars intermedia
A
ADENOHYPOPHYSIS
13
Q
- Pars nervosa (infundibular process)
- Infundibular stem (stalk)
- Median eminence of tuber cinereum
A
NEUROHYPOPHYSIS
14
Q
- Also known as the hypophysis cerebri.
- The hypophysis is a pea-sized glandular organ lodged in the hypophyseal fossa of the sella tursica of the body of the sphenoid.
- It is connected by the infundibulum stalk to the base of the brain and is covered by a capsule of dense connective tissue.
A
PITUITARY GLAND
15
Q
Divisions of the Hypophysis
A
- Adenohypophysis
- Anterior part derived from the Rathke’s pouch
- An outgrowth from the ectodermal roof of the primitive oral cavity - Neurohypophysis
- Posterior part developed as a downgrowth from the floor of the diencephalon
16
Q
- Also known as the anterior pituitary
- Subdivisions:
- Pars distalis
- Pars intermedia
- Pars tuberalis
A
Adenohypophysis
17
Q
- Largest subdivision of the adenohyphysis.
- The cells are grouped into 2 categories:
1. Chromophils
2. Chromophobes
A
PARS DISTALIS
18
Q
Chromophils
A
2 types of cells based on affinity to stains
- Acidophils – secrete prolactin and growth hormone
- Basophils - secrete FSH, LH, TSH, ACTH
19
Q
- Smallest and least numerous among the cells in the pars distills
- Since they are small, their nuclei lie close to each other; and their cytoplasm is scanty, thus hardly seen.
- These cells are referred to as reserve cells since some of them may differentiate into acidophils or basophils as the need arises
A
Chromophobes
20
Q
Stimulates release of Thyrotropin (TSH)
A
Thyrotropin releasing hormone (TRH)
21
Q
Stimulates release of FSH and LH
A
Gonadotropin releasing hormone (GnRH)
22
Q
Inhibits release of both GH and TSH
A
Somatostatin
23
Q
Stimulates release of GH
A
Growth hormone-releasing hormone (GHRH)
24
Q
Inhibits release of Prolactin
A
Dopamine
25
Stimulates synthesis of pro-opiomelanocortin (POMC) and release of both B-lipotropin and ACTH
Corticotropin-releasing hormone
26
% Total cells: 50
Hormone produced: SOMATOTROPIN (GROWTH HORMONE)
Major Function: Stimulates growth in epiphyseal plates of long bones via insulin-like growth factors (IGF) produced in liver
Somatotrophs
27
% Total cells: 15-20
Hormone Produced: PROLACTIN (PRL)
Major function: Promotes milk secretion
Lactotrophs or Mammotrophs
28
% Total cells: 10
Hormone Produced: FSH, LH, ICSH (Interstitial cell-stimulating Hormone)
Major Function: FSH promotes ovarian follicle devt and Estrogen secretion in women and spermatogenesis in men: LH promotes ovarian follicle maturation and Progesterone secretion in women and interstitial cell androgen secretion in men
Gonadotrophs
29
% Total cells: 5
Hormone Produced: THYROTROPIN (TSH)
Major Function: Stimulate TH synthesis, storage and liberation
Thyrotrophs
30
% Total cells: 15-20
Hormone Produced and Functions:
*ADRENAL CORTICOTROPIN (ACTH) - Stimulates secretion of adrenal cortex hormones
*LIPOTROPIN (LPH) - Helps regulate lipid metabolism
Corticotrophs
31
- It is found between the pars distalis and the infundibular process.
- It is characterized by the presence of follicles or cysts filled with colloid and lined by columnar epithelium, which are called RATHKE’S CYST.
- Also found are polygonal basophilic cells.
PARS INTERMEDIA
32
The hormone of the pars intermedia is the __, which causes the dispersion of melanin pigments in the melanoblast and increase the pigmentation of the skin.
melanocyte stimulating hormone (MSH)
33
- most highly vascular portion of the hypophysis.
- is formed of longitudinal columns or cords of cells that descend towards the pars distalis.
- The cell types are:
1. Undifferentiated cells
2. Small basophils and acidophils
- There is NO HORMONE isolated in this area
PARS TUBERALIS
34
- It is formed of venules that connect the capillaries in the median eminence with the capillary sinusoids in the pars distalis. It is thru the HYPOPHYSEAL PORTAL CIRCULATION that the releasing hormones from the hypothalamus reach the secretory cells of the pars distalis.
- The neurohormones from the hypothalamus reach the pars distalis through nerve fibers.
- The blood supply of the hypophysis is derived from the SUPERIOR HYPOHYSEAL ARTERIES, branches of the internal carotid and branches of the posterior communicating arteries
HYPOPHYSEAL SYSTEM
35
- is formed of unmyelinated nerve fibers of the hypothalamo-hypophyseal tract, which are formed of axons of the neurons in the hypothalamic nuclei.
- The axons descend through the median eminence to the infundibular stalk and infundibular process.
neurohypophysis
36
Also found in the neurohypophysis, part of the pars nervosa, are the __ – cells with numerous processes and are considered as modified neuroglial cells.
pituicytes
37
(neurohypophysis)
- are small, spherical structures containing NEUROHORMONES ( ADH AND OXYTOCIN) stored in the PARS NERVOSA or in the infundibular process. These are neurosecretory materials secreted by the neurons in the hypothalamic nuclei and travel along the axons of these neurons to be stored and released from the axolemma of the nerve fibers.
Herring bodies
38
Hormones in the Pars Nervosa
Found in the infundibular process or pars nervosa (Posterior pituitary DOES NOT contain the cells that synthesize its 2 hormones)
1. Pitocin (Oxytocin)
2. Pitressin or ADH (Anti-Diuretic Hormone)
39
(pars nervosa)
- Synthesized by the paraventricular nuclei of the hypothalamus
- Stimulates uterine contraction and mammary gland
Pitocin (Oxytocin)
40
(pars nervosa)
- Synthesized by the supraoptic nuclei of the hypothalamus
- Increase water retention
Pitressin or ADH (Anti-Diuretic Hormone)
41
Development of the Thyroid Gland
- Develops from epithelial proliferation in the floor of the pharynx between the tuberculum impar and copula, at a point later indicated by the foramen cecum.
- It descends in front of the pharyngeal gut as a bilobed diverticulum. This is connected to the tongue by a narrow canal, the THYROGLOSSAL DUCT, which later disappears. The cystic remnants of the thyroglossal duct is called the THYROGLOSSAL CYST.
- The 5th pharyngeal pouch gives rise to the ULTIMOBRANCHIAL BODY, which later is incorporated in the thyroid gland. The cells of the ultimobranchial body give rise to parafollicular or C-cells of the thyroid gland secreting calcitonin.
42
- found in the anterior part of the neck, consisting of two lobes connected by a narrow ISTHMUS, which crosses the trachea just below the cricoid cartilage.
- has a CONNECTIVE TISSUE CAPSULE that is continuous with the surrounding cervical fascia. The outer capsule is loosely on its deep surface of another layer of moderately dense connective tissue that is intimately adherent to the gland.
Thyroid Gland
43
- The structural unit is the spherical cystlike follicles, which are lined by SIMPLE CUBOIDAL EPITHELIUM and containing a gelatinous COLLOID.
- This represents the stored product of secretory activity by the lining epithelium.
- The FOLLICULAR CELLS are surrounded by a thin basal lamina.
- The epithelial cells vary in height, but are commonly cuboidal, squamous when the gland is hypoactive and columnar when it is hyperactive.
- The nucleus is spherical, centrally located, poor in chromatin and contain one or more nucleoli
Thyroid Gland
44
(Thyroid Gland)
These were originally called __ based on their position, but with the discovery that they produce CALCITONIN, they are now called C-cells. Other names are LIGHT CELLS, MITOCHONDRIA-RICH CELLS AND ULTIMOBRANCHIAL CELLS
parafollicular cells
45
Functions of the Thyroid Gland
- Synthesize, store and release hormones concerned with the regulation of metabolic rate (TRI-IODOTHYROXINE OR T3 AND TETRA-IODOTYROXINE OR T4) by the follicular epithelial cells. (TH increase metabolic rate)
- Decrease blood calcium level by the C-cells or parafollicular cells through the secretion of calcitonin. (inhibits osteoclast activity)
46
Development of the Parathyroid Gland
It develops from:
1. Superior parathyroid- Dorsal wing of the 4th pharyngeal pouches
2. Inferior parathyroid - Dorsal wing of the 3rd pharyngeal pouches
47
- These are two pairs of glands which are small, yellow-brown oval bodies adhering to the posterior surface of the thyroid gland.
- A connective tissue capsule separates them from the thyroid gland.
- Delicate connective tissue septa partially divide the gland into poorly defined lobules and still finer ones separate the epithelial cells into anastomosing cords and groups.
PARATHYROID GLAND
48
PARATHYROID GLAND
The parenchyma is composed of two types of cells:
1. PRINCIPAL OR CHIEF CELLS
- Constant occurrence
- Polyhedral cells with round nuclei, with loosely arranged chromatin giving a vesicular appearance, and basophilic cytoplasm
2. OXYPHIL CELLS
- Appears only at the end of the first decade of life until puberty
- Larger cells with smaller and darker nuclei and acidophilic cytoplasm
49
The parathyroid glands regulate __ concentration by stimulating resorption of bone and reabsorption of calcium ions from ultrafiltration of the kidneys and with the aid of the vitamin D absorption of calcium from the gut.
calcium
50
Through the principal cell secretion of parathyroid hormone (PTH), blood calcium level increases.( by stimulatng osteoclast activity)
Parathyroid gland
51
Development of the Adrenal Gland
Adrenal cortex
- About the 5th week of development, MESOTHELIAL CELLS proliferate and later differentiate into large acidophilic structures forming the primitive or fetal cortex of the adrenal gland
- Shortly later, a second wave of cells from the mesothelium penetrate and surround the original acidophilic mass. These cells will form the definitive cortex of the adrenal gland.
Adrenal medulla
- Arises from NEURAL CREST CELLS. These cells invade the medial aspect and become cords and clusters forming the medulla of the adrenal gland.
- The cells of the adrenal medulla are stained yellowish brown with chrome salts. Hence, they are called CHROMAFFIN CELLS.
52
- The paired glands are roughly triangular, flattened organs embedded in the retroperitoneal fat tissue at the cranial pole of each kidney.
- It has a thick capsule of connective tissue that extends into the cortex as trabeculae.
- There are two functionally and structurally distinct parts:
1. Cortex
2. Medulla
ADRENAL GLANDS
53
ADRENAL GLANDS
- The principal secretory cells of the MEDULLA ARE derived from the NEURAL CREST CELLS.
- The secretory cells of the CORTEX are derived from the MESODERMAL CELLS IN THE NEPHROGENIC RIDGE.
54
- The cortex forms the bulk of the gland.
- It has three distinguishable concentric zones:
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis
ADRENAL CORTEX
55
- Adjacent to the capsule is a narrow zone in which the cords of columnar cells are in ovoid groups.
- There is no central cavity within a cell group as in exocrine glands, but there is a rich network of blood vessels externally.
- It produces ALDOSTERONE
ZONA GLOMERULOSA
56
a potent mineralocorticoid causing water and sodium retention in exchange for potassium in the kidney.
ALDOSTERONE
57
- The middle and broadest zone is composed of cell cords coursing parallel to one another in radial direction toward the medulla.
- The secretory cells are cuboidal or polyhedral, and sometimes binucleated, which are vesicular.
- These cells secrete GLUCOCORTICOIDS , especially CORTISOL
ZONA FASCICULATA
58
- Network of cell cords, which are smaller than those of the fasciculata, darker nuclei, fewer lipid droplets and numerous lipofucshin granules.
- Also produce CORTISOL but primarily secrete Weak Androgens including DEHYDROEPIANDROSTERONE (DHEA) – precursors for testosterone and Estrogen
- It is probable that the outer part of the fasciculata produces much of the cortisol in unstressed individuals.
ZONA RETICULARIS
59
- the most important glucocorticoid, has a protein wasting effect and promotes gluconeogenesis; suppress immune cell activities
Cortisol
60
- The secretory cells ( Chromaffin cells) here are in anastomosing groups associated with blood vessels.
- The parenchymal to columnar, and contain cytoplasmic granules, which become brown when oxidized by potassium bichromate.
- The chromaffin reaction of the granules is due to their content of CATECHOLAMINES – EPINEPHRINE AND NOREPINEPHRINE.
ADRENAL MEDULLA
61
increases the heart rate and cardiac output without signifying increasing the blood pressure and other metabolic effects; constricts vessels
Epinephrine
62
is in the brain and peripheral tissues, the principal transmitter substance of adrenergic neurons; dilates vessels and increases glucose release
Norepinephrine
63
Development of the Pineal Gland
- The pineal gland develops from the caudal part of the roof of the diencephalon.
- It appears as an epithelial thickening on the midline by the 7th week of development.
- Then, it invaginates to become a solid organ located at the roof of the mesothelium.
64
- Also known as EPIPHYSIS CEREBRI.
- is a slightly flattened cone shape appendage of the brain, attached to the roof of the 3rd ventricle by the peduncle.
- made up of pale staining epitheloid cells, with round or oval granular nuclei and prominent nucleoli, the PINEALOCYTES.
PINEAL GLAND
65
(pineal gland)
- second cell type which occur in the perivascular areas.
- less numerous and the nuclei are darker and smaller.
- neuroglial cells provide supporting network to the cells.
interstitial cells
66
are mulberry shaped concretions largely of hydroxyapatite, which makes the radiological landmark.
Brain sand (corpora arenacea or Psammoma’s bodies)
67
- The gland reaches its’ maximal development by the middle of the first decade and regresses later in life.
- It has a high level of SEROTONIN AND MELATONIN SECRETED by the pinealocytes.
- controls the onset of puberty; regulates circadian rhythms
pineal gland
68
- has an exocrine portion, which secretes digestive juice essential for the digestion of carbohydrates, fats and proteins, and an endocrine portion secreting hormones.
- The endocrine function is performed by a highly vascularized aggregation of secreting cells, the ISLETS OF LANGERHANS, which are scattered all throughout.
- They are over a million, but comprised only one to two per cent of the gland.
Pancreas
69
Development of the Islets of Langerhans
- The islets of Langerhans develops from the parenchymatous pancreatic tissue during the 3rd month of development and scattered throughout the gland.
- Insulin secretion begins on the 5th month of development
70
- The islets are spheroidal masses of pale staining cells arranged in a form of irregular anastomosing cords, with a few fine connective tissue fibers.
- They are more abundant in the tail of the pancreas.
- The secretion is released into the interstitium where it has access to the bloodstream.
- By special methods, there are six cell types distinguished.
Islets of Langerhans
71
Principal Cells of the Islets of Langerhans
1. Alpha cells - Periphery, Secrete GLUCAGON ( increase blood glucose )
2. Beta cells - Predominant type distributed throughout the islet comprising 60% to 90% of its mass, Secrete INSULIN (decrease blood glucose levels)
3. Delta cells - Least abundant occurring anywhere in the islet, Secrete SOMATOSTATIN ( inhibit secretion of insulin,glucagon and somatotropin)
4. Pancreatic polypeptide – rare, + gastric chief cells; inhibit bile secretion,pancreatic enzyme&bicarbonate secretion and intestinal motility
72
- is a compound tubular gland enclosed in a thick fibrous capsule, the TUNICA ALBUGINEA. Thin fibrous septa, the SEPTULA TESTIS, extend radially dividing the organ into compartments, the LOBULI TESTIS.
- Each lobule is composed of one to four highly convoluted seminiferous tubules, which constitute to the exocrine portion of the __
TESTES
73
Development of the Leydig Cells of Testis
- Develops from the mesenchyme between the seminiferous tubules, which are particularly abundant during the 4th to 6th months of development.
74
- endocrine component of the testis that are located in the interstices between the seminiferous tubules. The cells occur in groups of various sizes. Small blood vessels are usually present. The cells are LARGE AND OVOID OR POLYGONAL. They have a LARGE ECCENTRIC NUCLEUS AND GRANULAR ACIDOPHILIC CYTOPLASM, which is peripherally vacuolated. The ultrastructure typifies that of steroid secreting cells which have extensive smooth endoplasmic reticula. Peculiar to human, is a variable number of proteinaceous crystals, Reinke’s crystals.
- synthesize TESTOSTERONE
Leydig cells
75
- are slightly flattened, ovoid, paired organs suspended on either side of the uterus.
- has two zones; a central deeper zone, the MEDULLA, and a broad outer zone, the CORTEX.
- As the follicles increase in size, the theca folliculi differentiates into a highly vascular inner layer of secretory cells, the THECA INTERNA, which secretes ESTROGEN, and an outer layer, the theca externa, composed mainly of connective tissue.
ovaries
76
Development of the Theca Interna Cells of the Ovary
Develop from secondary cortical cords from the proliferation of cells in the stroma ovarii
77
Following ovulation, the follicular wall collapses and its granulosa cell lining is thrown into folds. There is extravasation of blood from the capillaries of the theca interna, resulting in a central clot. The theca interna and granulosa cells then enlarge and accumulate lipid and are transformed into plump, pale staining polygonal cells, the LUTEIN CELLS. This structure is now called the __
Corpus luteum
78
(ovary)
| Two kinds of Lutein cells are distinguishable which are
1. the peripheral, smaller and darker stained THECA LUTEIN CELLS, which secrete a small amount of ESTROGEN
2. larger, GRANULOSA LUTEIN CELLS, which secrete PROGESTERONE
79
(placenta)
The syncitiotrophoblast of the chorionic villi secrete __
Human chorionic gonadotrophic hormone (HCG)
80
- special type of connective tissue in which fat cells predominate
- ound isolated in all loose connective tissue, but in certain places they are present in such large numbers and have such organization as to justify the designation of adipose tissue.
- are large, oval or spherical shaped cells, whose cytoplasm is displaced to the peripheral region of the cell by the presence of a single large fat droplet . The nucleus is flattened and surrounded by a small amount of cytoplasm in the periphery giving a characteristic “signet ring” appearance.
Fat
81
The principal functions of adipose tissue are:
1. Storage of fat
2. Insulation against heat loss
3. Mechanical support in certain body regions
82
There are two types of adipose tissue, namely:
1. Yellow or white adipose tissue
- Common or yellow or white adipose tissue comprise the bulk of the body fat.
- It is an adult fat or mature form of adipose tissue from which ranges in color from white to dark yellow.
- The adipose cell contains a single large fat droplet in the cytoplasm. Therefore, it is unilocular as to morphology.
This type is found in subcutaneous tissue of skin, omentum, mesenteries and retroperitoneal fat.
2. Brown adipose tissue
- is a fetal fat or immature form of adipose tissue
- color ranges from tan to reddish brown; cell contains multiple lipid droplets in the cytoplasm; hence, it is multilocular in morphology.
- is found in the interscapular and inguinal regions of the newborn
83
Endocrine function of adipose tissue
Major site for metabolism of sex steroid and glucocorticoid
84
(kidney)
- have a slightly basophilic cytoplasm and their specific granules are clearly demonstrated. Electron microscopy of secretory granules shows that cells are variable in shape and membrane bounded with an internal crystalline structure.
- cells secrete RENIN, which activates Angiotensinogen into Angiotensin I. Angiotensin I is inactive but is converted in the lungs to Angiotensin II, which is a potent vasoconstrictor, increasing blood pressure.
Juxta-glomerular (JG) cells
85
(kidney)
- Also known as polar cushion or polkissens cells. These cells are formed at one angle between the afferent and efferent arteriole at the vascular pole.
- They may produce ERYTHROPOIETIN, a hormone that stimulates erythropoiesis in the bone marrow.
Lacis cells or extraglomerular mesangial cells
86
- Located posterior to the sternum
- Largest in infants and children
- Produces THYMOSIN
* Matures some types of white blood cells
* Important in developing the immune system
Thymus
87
Pituitary Dwarfism vs Gigantism vs Acromegaly
Pituitary dwarfism - hyposecretion of growth hormone by the adenohypophysis
Gigantism - hypersecretion of growth hormone during childhood
Acromegaly - hypersecretion of growth hormone during adulthood
88
hyposecretion of ADH caused by damage to the neurohypophysis or the supraoptic nucleus
Diabetes insipidus
89
a heterogenous group of diseases, all of which lead to an elevation of blood sugar and excretion of glucose in the urine
Diabetes mellitus
90
Cretinism vs Myxedema vs Grave's Disease
Cretinism = hyposecretion of thyroid hormones during the growth years. Two clinical manifestations of the cretin are dwarfism and mental retardation
Myxedema = hypothyroidism during adulthood. Hallmark of this disorder is an edema that causes the facial tissues to swell and look puffy
Grave’s disease = hyperthyroidism during adult life. This gives rise to exophthalmic goiter.
91
Tetany vs Osteitis fibrosa cystica
Tetany = muscle twitches or spasm and convulsions as a result of hypoparathyroidism (deficiency in calcium)
Osteitis fibrosa cystica = hyperparathyroidism that causes demineralization of bone
92
hypersecretion of the mineralocorticoid, aldosterone, characterized by a decrease in the body’s potassium concentration
Aldosteronism
93
primary adrenal insufficiency that results in hyposecretion of glucocorticoids. Clinical manifestations include lethargy, weight loss and hypoglycemia, which leads to muscular weakness
Addison’s disease
94
hypersecretion of glucocorticoids, especially cortisol and cortisone. Clinical manifestations include moon face, buffalo hump on the back and pendulous abdomen
Cushing’s syndrome
95
tumor of the chromaffin cells of the adrenal medulla, causes hypersecretion of the medullary hormones
Pheochromocytoma
96
The __ is formed from the incorporation of the dorsal part of the yolk sac into the embryo due to the craniocaudal folding and lateral folding of the embryo.
primitive gut tube
97
The primitive gut tube extends from the oropharyngeal membrane to the cloacal membrane and is divided into the __
foregut, midgut, and hindgut
98
Histologically, the general plan of the adult gastrointestinal tract consists of a __
1. mucosa (epithelial lining and glands, lamina propria, and muscularis mucosal)
2. submucosa
3. muscular externa
4. adventitia or serosa.
99
Embryologically, the epithelial lining and glands of the mucosa are derived from __, whereas the other components are derived from visceral mesoderm.
endoderm
100
- derivatives are supplied by the celiac trunk except esophagus
- lies caudal to the pharyngeal tube and extends as far caudally as the liver outgrowth
- extends from the esophagus down to the second part of the duodenum where the common bile duct enters the GI tract
- consists of esophagus, stomach, liver, gallbladder, pancreas, proximal duodenum, trachea, oropharynx and salivary gland
Foregut
101
- The middle part remains temporally connected to the yolk sac by means of the vitelline duct, or yolk stalk
- extends to the junction of the middle and distal thirds of the transverse colon (known as CANNON’S POINT)
- begins caudal to the liver bud and extends to the junction
- supplied by the superior mesenteric artery
- consists of lower duodenum, jejunum, ileum, cecum, appendix, ascending colon and proximal 2/3 of the transverse colon
midgut
102
- extends from the left third of the transverse colon to the
cloacal membrane
- supplied by the inferior mesenteric artery
- consists of Distal 1/3 of the transverse colon, descending colon, sigmoid colon, rectum, and upper anal canal
hindgut
103
- occurs when the tracheoesophageal septum deviates too far dorsally, causing the esophagus to end as a closed tube. - About 33% of patients with __ also have other congenital defects associated with the VATER (vertebral defects, anal atresia, tracheoesophageal fistula, and renal defects) or VACTERL (similar to VATER plus cardiovascular defects and
upper limb defects) syndromes
- It is associated clinically with polyhydramnios (the fetus is unable to swallow amniotic fluid) and a tracheoesophageal fistula
- esophagus terminates blindly in a blunted esophageal pouch. There is a distal esophageal connection with the trachea at the carina
Esophageal atresia
104
- occurs when the lumen of the esophagus is narrowed and usually involves the midesophagus.
- may be caused by submucosal/muscularis externa hypertrophy, remnants of the tracheal cartilaginous
ring within the wall of the esophagus, a membranous diaphragm obstructing the lumen probably due to incomplete recanalization.
Esophageal stenosis
105
- occurs when abdominal contents herniates through the
umbilical ring and persists outside the body, covered variably by a translucent peritoneal membrane sac (a light gray, shiny sac) protruding from the base of the umbilical cord.
- Large __ may contain stomach, liver, and intestines. Small __ contain only intestines.
Omphalocele
106
- occurs when there is a defect in the ventral abdominal wall, usually to the right of the umbilical ring, through which there is a massive evisceration of intestines (other organs may also be involved). The intestines arenot covered by a peritoneal membrane, are directly exposed to amniotic fluid, are thickened, and are covered with adhesions.
Gastroschisis
107
- occurs when the anal membrane fails to perforate; a layer of tissue separates the anal canal from the exterior.
Imperforate anus
108
- occurs when the anal canal ends as a blind sac below the puborectalis muscle due to abnormal formation of the urorectal septum.
- It is usually associated with rectovesical, rectourethral, or rectovaginal fistula.
Anal agenesis
109
- occurs when the rectum ends as a blind sac above the puborectalis muscle due to abnormal formation of the urorectal septum.
- It is the most common type of anorectal malformation and is usually associated with a rectovesical, rectourethral, or
rectovaginal fistula
Anorectal agenesis
110
- occurs when both the rectum and anal canal are present but remain unconnected due to either abnormal recanalization or a compromised blood supply causing focal atresia.
Rectal atresia
111
Derivation of Adult Mesenteries
1. VENTRAL - Lesser omentum (hepatoduodenal and hepatogastric ligaments), falciform ligament of liver, coronary ligament of liver, triangular ligament of liver
2. DORSAL - Greater omentum (gastrorenal, gastrosplenic, gastrocolic, and splenorenal ligaments), mesentery of small intestine, mesoappendix, transverse mesocolon, sigmoid mesocolon
112
- digestive tract and accessory organs
| - oral cavity to anus
Digestive system
113
Functions of the Digestive System
Primarily involved in breaking down food for absorption into the body
This process occurs in five phases:
a. ingestion
b. fragmentation
c. digestion
d. absorption
e. elimination of waste products
114
is lined by stratified squamous non-cornified epithelium, except for the hard palate, gingivae and filiform papillae of the tongue which are cornified.
oral cavity
115
Boundaries of the Oral Cavity
Anteriorly - lips
Posteriorly - facial isthmus
Superiorly - hard and soft palate
Inferiorly - floor of the mouth, including the tongue
116
- is present only in certain regions like the lips, cheeks and soft palate.
- In the hard palate, there is no __. In the hard palate, the mucosa is firmly bound to the periosteum of the underlying bone.
submucosa
117
Subdivisions of the Oral Cavity
1. Oral Vestibule - A cleft-like interval between the gums and teeth internally and the lips and cheeks externally
2. Oral Cavity Proper - A large cavity between behind the the gums and teeth
118
- is the only communication between the oral vestibule and oral cavity proper when the mouth is closed and the teeth are clenched.
- This space is located between the last two molars and the ramus of the mandible.
retromolar space
119
Structures in the Oral Cavity
- Lips
- Cheeks
- Tongue
- Gums
- Teeth
120
Lips
- Consists of upper and lower lips
Layers are:
1. Skin- Lined by stratified squamous cornified epithelium
2. Superficial fascia
3. Submucosa - Contains tubulo-alveolar small salivary glands called labial glands with mixed secretions
4. Mucosa
- Lined by stratified squamous non-cornified epithelium
- Vermillon border muco-cutaneous junction where there is an abrupt transition of epithelia
- Absence of hair follicles, sweat and sebaceous glands
121
Cheeks
1. Skin - Lined by stratified squamous cornified epithelium
2. Superficial fascia - With buccal pad of fat
3. Bucco-pharyngeal fascia - Investing the buccinator muscle
4. Buccinator muscle
5. Submucosa - Contains tubulo-alveolar small salivary glands called buccal glands of mixed secretions
6. Mucosa - Lined by stratified squamous non-cornified epithelium
122
The gastrointestinal tract has four distinct
| functional layers:
mucosa, submucosa, muscularis propria and adventitia.
123
- is made up of three components: the epithelium, a supporting lamina propria and a thin smooth muscle layer, the muscularis mucosae, which produces local movement and folding of the mucosa. At four points along the tract, the __ undergoes abrupt transition from one form to another: the gastrooesophageal junction, the gastroduodenal junction, the ileocaecal junction and the rectoanal junction.
Mucosa
124
This layer of loose collagenous connective tissue supports the mucosa and contains the larger blood vessels, lymphatics and nerves.
Submucosa
125
The muscular wall proper consists of smooth muscle that is usually arranged as an inner circular layer and an outer longitudinal layer. In the stomach only, there is an inner oblique layer of muscle. The action of the two layers, at right angles to one another, is the basis of peristaltic contraction.
Muscularis propria
126
This outer layer of loose supporting tissue conducts the major vessels, nerves and contains variable adipose tissue.
Where the gut lies within the abdominal cavity (peritoneal
cavity), the -- is referred to as the serosa (visceral peritoneum) and is lined by a simple squamous epithelium (mesothelium). Elsewhere, the __ layer merges with retroperitoneal tissues.
Adventitia
127
- Mobile muscular (skeletal muscle) structure
- The upper surface of the __ (dorsum) is rough which contains lingual papillae.
- The dorsum of the -- is divided by a V – shaped groove called the sulcus terminales into an anterior 2/3 (palatine portion) and posterior 1/3 (pharyngeal portion)
Tongue
128
Four Types of Lingual Papillae
1. Filiform papillae
2. Fungiform papillae
3. Foliate papillae
3. Circumvallate papillae
129
- Most numerous
- Arranged in distinct rows diverging to the right and left from the midline and parallel to the sulcus terminals
- Contain finger-like projections containing a core of dense
collagenous tissue and lamina propria
- DO NOT HAVE TASTE BUDS
- Lined by stratified squamous cornified epithelium
“Ano yung dapat maalala dito? WALANG taste buds, siya din ang cornified”
Filiform Papillae
130
- Have a constricted base and an expanded surface
- Found mostly at the tips of the tongue
- Contain taste buds
- Lined stratified squamous non-cornfied epithelium
“Mushroom form, yung base maliit, yung head malaki”
Fungiform Papillae
131
- Rudimentary in man
- Leaf-like papillae with ridges
- Usually found at the dorsolateral margin of the tongue
- Contain taste buds
- Lined by stratified squamous non-cornified epithelium
“Are taste buds that look like leaves”
Foliate Papillae
132
- Largest of the lingual papillae
- Usually found in front of the sulcus terminalis arranged in rows and arranged in numbers from 1 – 12
- Contain taste buds
- Lined by stratified squamous non-cornified epithelium
Circumvallate Papillae
133
- the under surface of the tongue contains small salivary glandscalled lingual glands namely:
*Anterior lingual glands (Blandin and Nuhn - mucoserous
glands)
*Posterior lingual glands (von-Ebners purely serous glands)
Lingual Glands
134
- Lined by stratified squamous cornified epithelium
| - The mucosa is firmly adherent to the mucoperichondrium or mucoperiosteum, which is formed of dense collagenous tissue
GUM
135
Two sets of teeth:
1. Temporary
- Deciduous or milk teeth
- 20 in number
- Erupts from the 6th month up to the 6th year
2. Permanent
- Erupts from the 6th year up to the 25th year
- 32 in number
136
Parts of a Tooth
1. Crown - Exposed portion
2. Neck - Between the crown and the root of the tooth
3. Root - Portion lodged inside the alveolar socket
137
Structure of a Tooth
1. Enamel - Hardest structure of the body; Secreted by ameloblasts
2. Dentin - Formed by odontoblasts
3. Cementum - Covers the dentin of the root; Secreted by cementocytes
4. Periodontal membrane - Serve to attach the root of the tooth to the alveolar socket; Formed by dense connective tissue
5. Pulp cavity - Contains blood vessels, nerves, fibroblasts, histiocytes and lymphatic vessels
138
The tissues of the teeth are derived from two embryological sources.
- The enamel is of epithelial (ectodermal) origin
| - The dentine, cementum, pulp and periodontal ligament are of mesenchymal (mesodermal)
139
Mucosa -> thrown into longitudinal folds giving the lumen an irregular or stellate shape
Layers:
- Lining epithelium
- Lamina propria
- Muscularis mucosa
- Submucosa
- Tunica muscularis (muscularis externa)
- Tunica adventitia
Esophagus
140
Esophagus
- Lining epithelium is lined by stratified squamous non-cornified epithelium
- At the esophago-gastric junction, the lining epithelium is squamo-columnar
141
(esophagus)
- Loose collagenous tissue
- Occasional lymphatic tissue
- Contains superficial esophageal glands or esophageal cardiac glands, which are branched coiled tubular glands lined by pale staining, mucus secreting columnar or cuboidal cells
Lamina propria
142
(esophagus)
– formed of a single layer of longitudinally arranged smooth muscle fibers
Muscularis mucosa
143
(esophagus)
- Dense irregular collagenous tissue
- Contains blood vessels, lymph vessels and nerves
- Contains MEISSNER’S PLEXUS
- Deep esophageal glands/esophageal glands proper are lined by pale staining mucus secreting columnar or cuboidal cells
Submucosa
144
(esophagus)
- Superficial and deep glands secrete mucus to lubricate mucosal surface to facilitate passage of food
* Dadalawa ang organ sa buong bituka, na mayroong submucosal glands. Isa doon ay si Esophagus… the other organ with your submucosal gland is your Duodenum.”
* Tanong ng bayan, How will you differentiate the Esophagus from your Duodenum? Go to your mucosa
Esophageal glands
145
(esophagus)
- Inner circular and outer longitudinal layer
- Upper 1/3 is composed of skeletal muscles only
- Middle 1/3 is composed of both smooth and skeletal muscles
- Lower 1/3 is composed of smooth muscle only
- Myenteric (Auerbach’s) plexuses are located in this layer
Muscularis externa
*Siya lang sa buong GUT ang may Skeletal Muscle
Tunica muscularis
146
(esophagus)
- Composed of loose connective tissue containing blood vessels and lymph vessels
Tunica Adventitia
*Meron bang mesentery ang esophagus? Syempre WALA. Nasa thorax pa yun eh. Kaya ADVENTITIA siya.
Tunica adventitia
147
Structural features with Functional features of Esophagus
Stratified squamous nonkeratinized epithelium - Resist abrasion
Mucous esophageal glands - Provide lubrication
Inferior constrictor muscle of pharynx and esophageal Sphincter - Function as upper and lower esophageal sphincter
Muscularis externa - Dysphagia associated with dysfunction and diseases of skeletal muscle; ineffective voluntary control of contraction; involuntary contraction
148
- Lining epithelium of the mucosa is lined by simple columnar epithelium without goblet cells
- Lamina propria of the mucosa is composed of loose connective tissue containing dense lymphatic tissue and occasional lymphatic nodules
- Gastric glands occupy the entire thickness of the lamina propria
Stomach
149
(stomach)
- Thrown into longitudinal folds or rugae which are more
prominent along the curvature
- Numerous, minute depressions called gastric pits or foveola gastricae are found on the surface of the mucosa
- Gastric glands in the lamina propriaa open into gastric pits
Mucosa
150
(stomach)
- Formed of two layers of smooth muscles
* Inner circular
* Outer longitudinal
Muscularis mucosa
151
(stomach)
- Formed of loose collagenous tissue containing blood vessels, lymph vessels and submucous plexus of Meissner
Submucosa
152
(stomach)
- Consists of 3 layers of smooth muscles
* Inner oblique
* Middle circular
* Outer longitudinal
“Sya lang ang may tatlong layer ng __”
Tunica muscularis
153
(stomach)
- Visceral peritoneal layer made of loose collagenous tissue
lined by mesothelium
*Anong pinagkaiba ni Tunica Adventitia at Tunica Serosa? THE PRESENCE OF MESENTERY.Pag merong mesentery,yung outermost layer mo ay SEROSA.Pagwala, ADVENTITIA siya.
Tunica serosa
154
Cells found in gastric glands
1. Mucous neck cells
2. Chief / Principal / Zygomatic cells
3. Parietal / Oxyntic cells
4. Endocrine cells
155
- Pale staining, mucous secreting columnar cells
Mucous neck cells
156
- Low columnar or cuboidal basophilic cells
| - Secrete pepsinogen
Chief / Principal / Zygomatic cells
157
- Characteristic cells of the stomach
- Big spheroidal or pyramidal shaped cells with acidophilic
cytoplasm found between the chief cells
- Secrete hydrochloric acid and intrinsic factor
Parietal / Oxyntic cells
158
- Argentaffin cells or entero-chromaffin cells
- Small pyramidal or flattened cells, irregularly scattered
between the other lining cells and the basement
membrane
- Have an affinity to silver and chromium stains
- Secrete serotonin, histamine and gastrin
- Belong to APUD cells
Endocrine cells
159
Three types of gastric glands (depending on location)
1. Cardiac Gland
2. Fundic Gland
3. Pyloric Gland
160
- Simple tubular glands (some are compound tubular
glands) with long coiled terminal ends
- Gastric pits are short and shallow
- The glandular cells are mostly mucous secreting cells
- There are few parietal cells and argentaffin cells
Cardiac glands
161
- Corpus glands
- Most numerous type of gland
- Simple branched tubular glands with slightly coiled
terminal ends
- Gastric pits are occupying ¼ thickness of mucosa
- Lumen is narrow, difficult to visualize
- All 4 types of cells are present
“Corpus = Body”
Fundic glands
162
- Simple branched tubular glands with extensively coiled
terminal ends
- Gastric pits are long and deep, extending to about half
the thickness of the mucosa
- Lumen is wider
- No parietal cells except in the pyloric sphincter
“Dito pinakamahaba na ang pits mo”
Pyloric glands
163
- This is the portion of the alimentary tract between the
stomach and the large intestines whose main function is
absorption.
- It has an average length of 22 feet.
- The lumen of the small intestines is widest in the
uodenum and narrowest near the ileocecal valve.
- The small intestines have 3 segments: duodenum,
jejunum and ileum.
Small Intestine
164
Layers of the small intestines
1. Mucosa
- Lining epithelium
- Lamina propria
- Muscularis mucosa
2. Submucosa
3. Tunica muscularis
4. Tunica adventitia
165
Mucosa of the Small interstines
Lining epithelium - Simple columnar epithelium with goblet cells
Lamina propria - Loose connective tissue
Muscularis mucosa - Thin layers of smooth muscle
166
(small intestine)
Loose connective tissue with blood vessels, lymph vessels and meissner’s plexus
Submucosa of the small intestines
167
(small intestine)
- Inner circular and outer longitudinal layers of smooth muscles
- Contains Auerbach’s plexus
Tunica muscularis of the small intestines
168
(small intestine)
- Loose collagen oud tissue containing blood vessels, lymphatic vessels and nerves
Tunica adventitia of the small intestines
169
(small intestine)
- This is thrown into transverse mucosal folds called the plicae circularis or valves of Kerkring, which have a core of submucosa.
- The intestinal villi are minute projections or outgrowths of the of the mucosa with a core of lamina propria.
Both the plicae circularis and intestinal villi serve to increase the absorptive surface.
*Ang intestinal villi at plicae circularis lumalabas sa labas ng
intestine habang pumapalaoob naman ang intestinal gland”
Intestinal Mucosa of Small Intestines
170
Crypts of Lieberkuhn
Invaginations of the lining epithelium forming simple tubular glands found between the bases of the intestinal villi
Four types of cells found:
1. Striated columnar cells
2. Goblet cells
3. Paneth cells
4. Endocrine cells
Intestinal Glands
171
- Tall cylindrical cells with an ovoid nucleus in the lower part of the cell
- Under electron microscopy, the striated border is made up of a large number of closely packed microvilli
Intestinal absorptive cells
172
- These are irregularly scattered among the absorptive cells.
- Their apical region is distended with mucigen droplets, while the base of these cells is relatively free of secretory materials and forms a slender stem or stalk.
- The nucleus tends to be flattened and the cytoplasm is strongly basophilic.
- The secretory product is mucus which serves to lubricate and protect the surface of the cytoplasm.
Goblet cells
173
- These cells are found in the base of the gland.
- These are pyramidal in shape with a round or oval nucleus near the base and secretory granules at the apical cytoplasm.
- The granules stain with acid dye and is acidophilic.
- secrete lysozyme.
Paneth cells
174
- Entero-endocrine or Argentaffin cells
- These are small cells that possess staining reaction similar to chromaffin cells of the adrenal medulla, which can also precipitate silver salts.
- They are found in the stomach and throughout the length of the intestines.
Endocrine cells
175
In the fundus and corpus of the stomach, these are labelled as EC cells, which secrete serotonin or 5-hydroxytryptamine, and ECL cells, which secrete histamine.
Endocrine cells
176
Subtype of Endocrine Cells
```
EC cells-serotonin
5-hydroxyptyramine and ECL cells –histamine
D-cells- somatostatin
A cells- glucagon
G cells- gastrin
L cells- glucagon like
S cells- Secretin
I cells-cholecystokinin
```
177
This is the shortest, the widest and the most fixed part of the small intestine and is largely retroperitoneal, closely attached to the dorsal wall of the abdomen.
“Safety feature ng __ ay ang BRUNNERS GLAND”
DUODENUM
178
Layers of Duodenum
1. Mucosa
- Lining epithelium
- Lamina propria
- Muscularis mucosa
2. Submucosa
3. Tunica muscularis
4. Tunica serosa
179
Mucosa of the Duodenum
Lining epithelium - Simple columnar epithelium with goblet cells
Lamina propria - Loose collagenous with dense lymphatic tissue and intestinal glands (crypts of Lieberkuhn)
Muscularis mucosa - Smooth muscle that separates the mucosa from the submucosa
180
(duodenum)
- Formed of dense collagenous tissue containing the Brunner’s glands or duodenal glands of Brunner.
- Brunner’s glands are branched, coiled tubular glands which secrete a viscous and alkaline fluid, whose principal function is to protect the mucosa against the erosive effect of the acid.
Submucosa of the Duodenum
181
Tunicae Muscularis and Serosa of the Duodenum
Tunica muscularis - Formed of an inner circular and outer longitudinal layering of muscles.
- Between these two layers are the myenteric or Auerbach’s plexus
Tunica serosa- Lined by mesothelium formed of flattened cells
182
JEJUNUM AND ILEUM
- The division into the jejunum and the ileum is arbitrary, since there is no point at which it may be said that the jejunum ends and the ileum begins.
- Both jejunum and ileum are lined by SIMPLE COLUMNAR
EPITHELIUM WITH GOBLET CELLS. They have the same layers as
that of the duodenum except for some differences.
183
```
Plicae circulars: Numerous / well Developed
Intestinal Villi: Leaf – like
Goblet Cells: Few
Mucosal Gland: Brunner’s gland
Lamina Propia: DLT / NLT (Nodular Lymphatic Tissue
Length: 10 in
Width: Widest
Mesentery: Absent
Mobility: Non-movable
```
Duodenum
184
```
Plicae Circularis: Less Numerous / Well developed
Intestinal Villi: Finger – like
Goblet Cells: Numerous
Mucosal Gland: Absent
Lamina Propia: DLT / NLT
Length: 8 ft
Width: Narrower
Mesentery: Present
Mobility: Movable
```
Jejunum
185
```
Plicae Circularis: Less Numerous / Well developed
Intestinal Villi: Club – shaped
Goblet Cells: More Numerous
Mucosal Gland: Absent
Lamina Propia: Peyer’s patches
Length: 12 Ft
Width: Narrowest
Mesentery: Present
Mobility: Movable
```
ileum
186
Extends from the ileo-cecal junction to the anal opening
It is about 5 – 6 feet long
Subdivided onto:
- Cecum and appendix
- Colon (ascending, transverse, descending and sigmoid)
- Rectum
- Anal canal
Large Intestines
187
Layers of the large intestines:
1. Mucosa
- Lining epithelium
- Lamina propria
- Muscularis mucosa
2. Submucosa
3. Tunica muscularis
4. Tunica serosa
188
Mucosa of the Large Intestines
- Comparatively smooth surface, since there are no villi.
- Mucosal folds referred to as plicae semilunaris.
* Lining epithelium - Simple columnar epithelium with goblet cells
* Lamina propria - Loose collagenous tissue with intestinal glands
* Muscularis mucosa- Smooth muscle that separates the mucosa from the submucosa
189
(large intestine)
Formed of dense collagenous tissue
Submucosa of the Large Intestines
190
Tunica muscularis of the large intestines
- In the appendix, rectum and anal canal, these are complete throughout with an inner circular and an outer longitudinal layer
- In the cecum and greater length of the colon, there is a
complete inner circular layer but the outer longitudinal layer is formed of 3 longitudinal flat bands called TAENIA COLI.
- In the living individual, the taenia coli are in a state of partial contraction causing the intervening portions of the wall to bulge outwards forming sacculations called HAUSTRA
191
(large intestine)
- Except for the cecum, appendix, transverse and sigmoid colon, which have a complete peritoneal covering, the rest of the parts of the large intestines are partially covered by peritoneum.
- In the anal canal, there is no peritoneal covering.
In the colon, the peritoneum may contain pouches with adipose tissue or fat called appendices epiplocae.
Tunica Serosa of the Large Intestines
192
A vermiform tubular appendix projecting from the cecum to the ileo-cecal valvae.
Appendix
193
Layers of the appendix
Mucosa
Lining epithelium = simple columnar with goblet cells
Lamina propria = contains dense lymphatic tissue and lymphatic nodules; intestinal glands are fewer and smaller
Muscularis mucosa = smooth muscle
Submucosa = contains lymphatic nodules with blood vessels and nerves
T. Muscularis = inner circular and outer longitudinal
T. Serosa = with peritoneal covering lined by mesothelium
194
- Extends from the sigmoid colon to the pelvic diaphragm
- Begins where the colon ceases to have a mesentery
- Usually occurs in front of the 3rd sacral vertebrae
- About 12 cm long
- Slightly dilated in its lower portion to form the rectal ampulla
Rectum
195
Layers of the Rectum
1. Mucosa
- Lining epithelium = simple columnar with goblet cells; goblet cells are most numerous in the rectum
- Lamina propria = contains transverse mucosal folds called plicae transversalis recti
- Muscularis mucosa = smooth muscle layer
2. Submucosa = formed of dense collagenous tissue with blood vessels and nerves
3. T. Muscularis = inner circular and outer longitudinal muscle layers
4. T. Serosa = found in the posterior wall
196
- represents the terminal portion of the large intestines and is about 1 ½ inches long.
- It runs downward and backward at right angle to the rectum through the fascia and between the 2 levators into the peritoneum, where it opens on the exterior at the anus.
- It has two portions:
1. Upper half
2. Lower half
anal canal
197
- Lined by simple columnar epithelium with goblet cells.
- There are longitudinal mucosal folds, called the anal COLUMNS OF MORGAGNI.
- The inner circular muscle thickens to form the internal anal sphincter which is an involuntary smooth muscle.
Upper Half of the Anal Canal
198
- Lined by stratified squamous non-cornified epithelium with goblet cells
- There are semilunar folds called the anal valves of Morgagni.
- It is in the anal opening that the stratified squamous epithelium becomes cornified.
- The lamina propria contains lymphatic tissue.
- The muscularis mucosa disappears in the lower half of the anal canal.
- The submucosa contains hemorrhoidal plexuses of veins.
- There is a circumferential annulus of striated or voluntary muscles called the external anal sphincter
Lower Half of the Anal Canal
199
- Branched tubulo-alveolar/acinar glands
- Secretes saliva into the oral cavity
- colorless liquid ( H2O, CHO, CHON, mucin, mineral salts and enzymes/lysozymes)
- Saliva is a hypotonic watery secretion containing variable amounts of mucus, enzymes (principally amylase and the antibacterial enzyme lysozyme), antibodies and inorganic ions.
- It is usually acidic, below pH 7 (pH6.7-7.4).
SALIVARY GLANDS
200
Two types of secretory cells are found in the salivary glands:
serous cells and mucous cells.
201
- are located between the basal plasma membranes of secretory cells and the basement membrane.
- These are flattened cells with long processes which extend around the secretory acinus; in section, they can only be recognised by their flattened nuclei lying within the basement membrane around the acinus
Myoepithelial cells
202
CLASSIFICATIONS OF SALIVARY GLANDS
1. Size – small or large
2. Secretions - serous, mucous or mixed
3. Site of opening of duct – oral vestibule or oral cavity
proper
203
Classification by SIZE
1. Small – Lingual Glands
Posterior lingual glands (Von Ebner’s gland)
-Found underneath the circumvallate
-mixed (serous and mucous)
Anterior lingual glands (Blandin’s gland) - mucous
2. Large – Parotid, Submandibular, Sublingual
204
Classification by secretion
Serous –watery, basophilic (dark)
Mucous –lipid, lightly stained
Mixed –serous demilunes can be seen
205
Classification by Site of Opening of Duct
Communication between oral vestibule and oral cavity: last molar
206
(DUCT SYSTEM OF LARGE SALIVARY GLANDS)
- Lined by cuboidal cells
- Round nucleus
- Interlobular; lumen is small
- The terminal secretory units merge to form small __ which are also lined by secretory cells
INTERCALATED DUCT
207
(DUCT SYSTEM OF LARGE SALIVARY GLANDS)
- Lined by columnar cells, eosinophilic cytoplasm and basal striations
- The basal cytoplasm appears striated, reflecting the presence of basal interdigitations of cytoplasmic processes of adjacent cells and associated columns of
mitochondria.
- The duct epithelium also secretes LYSOZYME AND
IMMUNOGLOBULIN (IG)A.
- In predominantly serous salivary glands, the __ are larger than in predominantly mucous glands, a feature associated with the role of the __ in modifying isotonic basic saliva to produce hypotonic saliva.
- It has a big lumen, round nucleus, tall columnar cells. It has basal striations.
SECRETORY/STRIATED DUCTS
208
(DUCT SYSTEM OF LARGE SALIVARY GLANDS)
- Simple columnar to Stratified columnar to stratified squamous
- connective tissue in between the lobules of the gland
- The lining of these ducts is unusual, combining various epithelial types, including simple cuboidal or columnar, stratified cuboidal or columnar, and pseudo pseudostratified epithelia, distributed in no apparent pattern.
- These atypical epithelia may reflect their composition of cells with many diverse functions, including cells for ion reabsorption, cells for secretion of mucin and other proteins, enteroendocrine cells, and basal stem cells, all in highly branched ducts of small diameter.
EXCRETORY DUCTS/INTERLOBULAR DUCTS
209
are polarized protein-secreting cells, usually pyramidal in shape, with round nuclei, well-stained RER, and apical secretory granules. Joined apically by tight and adherent junctions, serous cells form a somewhat spherical unit called an acinus (L. grape), with a very small central lumen
Serous cells
210
are somewhat more columnar in shape, with more compressed basal nuclei
- contain apical granules with hydrophilic mucins that provide lubricating properties in saliva but cause poor cell staining in routine preparations
- are most often organized as cylindrical tubules rather than acini.
Mucous cells
211
- are found inside the basal lamina surrounding acini, tubules, and the proximal ends of the duct system
- These small, flattened cells extend several contractile processes around the associated secretory unit or duct and their activity is important for moving secretory products into and through the ducts.
Myoepithelial cells
212
- Largest
- Main duct – STENSEN’S DUCT
- Purely serous gland
- consists mainly of serous secretory units which are darkly stained in H&E preparations. The serous cells SC have
numerous ZYMOGEN GRANULES.
o These are strongly stained cytoplasmic granules containing proteins. Their nuclei are rounded with
dispersed chromatin and they usually occupy a more
central position within the cell (compared to mucussecreting cell.)
o An intercalated duct ID with a lining of cuboidal secretory
cells can be seen.
PAROTID GLAND
213
- Second largest
- Main duct – WHARTON’S DUCT
- Mixed gland, predominantly serous
- With Serous demilunes of Gianuzzi
- of a mixture of serous and mucous secretory units which are often found in the form of mixed seromucous secretory units.
- The mixed secretory units consist of mucous acini M with serous demilunes SD.
SUBMANDIBULAR GLAND
214
- Under the tongue
- MAJOR DUCT – BARTHOLIN’S DUCT
- MINOR DUCT – RIVINUS
- Mixed gland, predominantly mucous
- With SEROUS DEMILUNES OF GIANUZZI
- No fibrous capsule
- Mucous acini predominate in the sublingual glands, making them stain very poorly with H&E
- A large excretory duct lined by a stratified cuboidal epithelium is present in the fibrous tissue septum. The duct is accompanied by blood vessels and nerves.
SUBLINGUAL GLAND
215
- Seen in the buccal mucosa layer, in the tongue and lips
| - it has watery secretions
Von Ebner’s Gland
216
- Largest internal organ;
- HEPATOCYTES: Key cells of this organ and arranged in rows/cords with 1-2 centrally located nucleus
- Main Digestive Function: BILE PRODUCTION for fat emulsification (Exocrine Function);
Liver
217
Other Functions of Liver
- Plasma protein synthesis like fibrinogen, prothrombin, albumin, apolipoproteins and transferring (Endocrine Function);
- Gluconeogenesis;
- Detoxification;
- Deamination;
- Glucose storage in the form of glycogen & triglycerides;
- Fat-soluble vitamin storage especially Vit. A;
- Removal of effete RBC;
- Storage of Iron.
218
The main functional cell in the liver is a type of epithelial
cell called the __. These cells are arranged as thin plates separated by fine vascular sinusoids through which blood flows. The close association of liver cells and the circulation allows absorption of nutrients from digestion, as well as secretion of products into the blood.
hepatocyte
219
is organized as thousands of small (~0.7 × 2 mm) hepatic lobules in which hepatocytes form hundreds of irregular plates arranged radially around a small central vein
liver parenchyma
220
Connects hepatocytes together
TIGHT JUNCTIONS
221
Blood flow into the liver sinusoids comes from terminal
branches of both the __. The liver is therefore unusual in having both arterial and venous blood supplies, as well as separate venous drainage
hepatic portal vein and hepatic artery
222
The outer surface of the liver is covered by a capsule composed of collagenous tissue C called__, covered by a layer of mesothelial cells M from the peritoneum.
Glisson’s capsule
223
Structure where the basal lamina is attached;
DESMESOMES
224
Center of a hepatic lobule;
Flow of blood: TOWARDS central vein;
Flow of bile: AWAY from central vein;
CENTRAL VEIN
225
Peripherally each lobule has three to six portal areas with more fibrous connective tissue, each of which contains three interlobular structures that comprise the portal
triad. What are the PORTAL TRIAD?
1. A VENULE BRANCH OF THE PORTAL VEIN, with blood rich in nutrients but low in O2,
2. An arteriole branch of the HEPATIC ARTERY that supplies O2,
3. One or two small BILE DUCTULES of cuboidal epithelium,
branches of the bile conducting system.
226
Between all the plates of hepatocytes of a hepatic lobule and contains mixed type of blood.
SINUSOIDS
227
- Discontinuous linings of fenestrated endothelial cells;
| - LE of simple squamous cells;
SINUSOIDAL BLOOD VESSEL
228
Why Sinusoidal BV discontinued and fenestrated?
- It allows to fill the SPACE OF DISSE (Perisinusoidal space) and directly bathes the many microvilli projections from the
hepatocytes;
- SPACE OF DISSE: Found between sinusoid and hepatocyte , and are rich in reticulin (stained with silver).
229
- Stellate macrophages from monocytes;
- Within the sinusoidal linings;
- Phagocytose aged RBCs;
- Antigen-presenting cells;
- Removes bacteria/debris in the portal blood
KUPFFER CELLS
230
- Hepatic stellate cells;
- Stores fat-soluble vitamins like Vit. A;
- Produces extracellular matrix and cytokines.
ITO CELLS
231
BILE FLOW:
Hepatocytes >>> Bile Canaliculi (smallest branch of the biliary tree) >>> Canals of Hering (composed of cholangiocytes) >>> Bile ductules (LE: simple cuboidal-columnar cells) >>> Hepatic ducts
232
Concepts of structure-function relationships in liver.
(a) The classic lobule
(b) The portal lobule
(c) The hepatic acinus
233
- Contains plenty of RER;
- For protein synthesis (Endocrine functions);
- Blood flows past hepatocytes from the portal areas to a central venue.
- concept offers a basic understanding of the structure function relationship in liver organization and emphasizes the endocrine function of hepatocytes as blood flows past them toward the central vein.
CLASSICAL HEPATIC LOBULE
234
- Contains plenty of peroxysomes;
- For detoxification and bile secretion (Exocrine functions);
- From one portal area to another portal area;
- Portal areas are rich in oxygen, nutrients and connective tissue.
- emphasizes the hepatocytes’ exocrine function and the flow of bile from regions of three classic lobules toward the bile duct in the portal triad at the center here. The area drained by each bile duct is roughly triangular.
PORTAL LOBULE
235
- Emphasizes the nature of blood supply to the
hepatocytes and the oxygen gradient from the hepatic
artery to central vein;
- For oxygen and nutrient supply;
- From one central vein to another central vein
HEPATIC ACINUS
236
ZONES in HEPATIC ACINUS
1. ZONE I - For oxidative metabolism such as protein synthesis; 1st to be affected during toxicity.
2. ZONE II - Intermediate metabolism between
Zone I and II.
3. ZONE III - Anaerobic metabolism; Preferential sites for glycolysis, lipid formation and drug biotransformations;
- 1st to be affected during low oxygen level;
- 1st to undergo fatty accumulation and ischemic necrosis.
237
- Compound tubo-acinar gland
- Endocrine and exocrine- produces both digestive enzymes and hormones
- Centroacinar cells - small, pale-staining
- Intercalated ducts - merge to form to form larger interlobular ducts; lined by columnar epithelium
PANCREAS
238
Endocrine and Exocrine Functions of Pancreas
ENDOCRINE FUNCTION
- ISLET OF LANGERHANS – cluster of epithelial cells where
hormones are synthesized
EXOCRINE FUNCTION
- Functional unit- SEROUS OR PANCREATIC ACINI (similar
structure to parotid gland, can be distinguished by
absence of striated ducts and presence of islets in
pancreas)
- Secretes 1.5 to 2L of fluid/day
- Pancreatic juice is rich in bicarbonate ions
239
- Pear-shaped hollow organ
| - Stores and concentrates bile
GALL BLADDER
240
Layers of Gall Bladder
1. Mucosa
LE: Simple columnar
LP: LCT, mucosal folds (Rokitansky Aschoff sinuses)
2. Fibromuscular layer - with bundles of muscle fibers oriented in all directions (transverse, oblique) to facilitate emptying
3. Perimuscular CN - DCT
4. Tunica Serosa - mesothelium where it is against the liver
241
is a muscular valve that controls the flow of digestive juices (bile and pancreatic juice) through the ampulla of Vater into the second part of the duodenum
sphincter of ampulla or sphincter of Oddi
242
Consists of 4 muscles of the Sphincter of Oddi
1. SPHINCTER CHOLEDOCHUS – surrounds and controls
terminal region of common bile duct, to stop flow
into duodenum
2. SPHINCTER PANCREATICUS – from pancreatic duct
3. SPHINCTER LONGITUDINALIS – triangular interval of
ampulla of Vater, pancreatic duct and common
bile duct
4. SPHINCTER AMPULLAE – from ampulla of Vater
243
- “Providing care that is respectful of and responsive to individual patient preferences, needs, and values – ensuring that patient values guide all clinical decisions.”
*Gauge patient’s preferred level of involvement
*Explore, where possible, therapeutic choices
*Utilize decisions aids
*Shared decision making – final decisions re: lifestyle
choices ultimately lies with the patient.
Patient Centered Approach
244
Background of the Study
- 382 million people had diabetes in 2013; by 2035 this will
rise to 592 million
- The number of people with Type 2 DM is increasing in
every country
- 80% of people with DM live in low- and middle-income
countries
- The greatest number of people with DM are 40-59 years
of age
- Diabetes: a huge and growing problem
245
What’s driving the diabetes epidemic?
- Aging population
- Unhealthy diet
- Obesity
- Sedentary lifestyle
- Socio-economic realities
- Urbanization, westernization and economic development
246
Who gets Type 2 Diabetes? People with:
- Age >= 30
- Obesity
- A family history of DM
- Physical Inactivity
- Pre-diabetes
- Race/Ethnicity
- High blood pressure or abnormal cholesterol levels
- PCOS (Polycystic Ovarian Syndrome)
247
Who gets Type 2 Diabetes? People who
- Had gestational diabetes
- Delivered large babies (>=8 lbs for Filipinos)
- Were born too small of too large
- Were born premature
- Have poor sleep
- Are on drugs like GLUCOCORTICOIDS, BETA BLOCKERS,
THIAZIDES, PHENYTOIN, ANTIPSYCHOTICS AND NICOTINIC ACID
248
Microvascular Complications of DM
1. Retinopathy - Leading cause of blindness in adults aged 20-74 years
- Most people with diabetes have some form of diabetic
retinopathy 30 years after diagnosis
2. Neuropathy - Around 50% of people with diabetes have some form of peripheral neuropathy
- Almost 30% of people with diabetes aged >=40 years
have impaired sensation in the feet
3. Diabetic nephropathy - Diabetes is the leading cause of kidney failure 25% prevalence 10 years after diagnosis
249
Macrovascular Complications
1. Stroke - People with diabetes are 2-4x more likely to have a stroke than people without
2. Cardiovascular disease - People with diabetes are 4x more likely to have a CVD event than people without
3. Peripheral artery disease - People with dibabetes are 15x more likely to have lower extremity amputation than people without
250
Key points of recent findings
- Intensive glucose control in newly diagnosed type 2
diabetes has benefits during intensive therapy an a
legacy effect for later micro- and macrovascular benefits
- Optimal glucose management should start as early as
possible and continue as long as possible
- While the A1C goal for the general population is
251
Pathogenesis of Type 2 DM: the TRIUMVIRATE
1. Impaired Insulin Secretion
2. Increased Hepatic Glucose Production
3. Decreased Glucose Uptake
252
Pathogenesis of Type 2 DM: Beta Cell Function Loss
Beta-cell function loss ~50%
- Individuals in the upper tertile of NGT
- 2-hour PG 120-139 mg/dL
Beta-cell fynction loss of ~70-80%
- Individuals in the upper tertile of IGT
- 2-hour PG 180-199 mg/dL
253
Pathogenesis of Type 2 DM: Disharmonious Quartet
1. Impaired Insulin Secretion
2. Increased Hepatic Glucose Production
3. Decreased Glucose Uptake
4. Increased Lipolysis
254
Pathogenesis of Fat Metabolism
- Fat cells resistant to insulin’s antilipolytic effect >>> elevation in the plasma free fatty acids (FFA)
- High plasma FFA >> gluconeogenesis/ muscle insulin
resistance, impaired insulin secretion (lipotoxicity)
- Excess insulin resistance-inducing inflammatory,
atherosclerosis-provoking adipocytokines; insufficient
insulin-sensitizing adipocytokines (eg adiponectin)
- Deranged fat cell metabolism
255
- Enlarged fat cells are insulin resistant and have diminished capacity to store fat
>> When adipocyte storage capacity is exceeded, lipid “overflows” into muscle, liver, B cells, even arterial vascular smooth cells
Altered fat topography
256
Pathogenesis of Type 2 DM: Quientessential Quintet
1. Impaired Insulin Secretion
2. Increased Hepatic Glucose Production
3. Decreased Glucose Uptake
4. Increased Lipolysis
5. Decreased Incretin Effect (intestinal secretion of insulin)
257
Attributed to the incretin effect which can be explained by
| 2 hormones:
1. GLP-1
- Secretion by L cells (iLeum) of the distal small intestine is deficient
- Deficient GLP-1 response contributes to the paradoxical rise in plasma glucagon and impaired suppression of HGP after meal ingestion
2. GIP
- Secretion by the K cells (duodenum/colon) of the more proximal small intestine is increased
- But there is resistance to GIP stimulation of
insulin secretion
258
Pathogenesis of Type 2 DM: Setaceous Sextet
1. Impaired Insulin Secretion
2. Increased Hepatic Glucose Production
3. Decreased Glucose Uptake
4. Increased Lipolysis
5. Decreased Incretin Effect
6. Pancreatic α-cell (increase in glucagon secretion)
259
Pathogenesis of Type 2 DM: Septicidal Septet
1. Impaired Insulin Secretion
2. Increased Hepatic Glucose Production
3. Decreased Glucose Uptake
4. Increased Lipolysis
5. Decreased Incretin Effect
6. Pancreatic α-cell
7. Increased Glucose Reabsorption in Kidneys
260
Most recent member implicated is the kidney (Septicidal Septet)
ADAPTIVE response by the kidney: conserve glucose to meet the energy demands of the body, especially the
brain and other neural tissues which have an obligate
need for glucose
MALADAPTIVE in the diabetic patient: instead of dumping glucose in the urine to correct hyperglycemia, the kidney chooses to hold on to glucose
261
Pathogenesis of Type 2 DM: Omnious Octet
1. Impaired Insulin Secretion
2. Increased Hepatic Glucose Production
3. Decreased Glucose Uptake
4. Increased Lipolysis
5. Decreased Incretin Effect
6. Pancreatic α-cell
7. Increased Glucose Reabsorption in Kidneys
8. Neurotransmitter Dysfunction
262
Brain insulin resistance
- Reduced satiety effect of insulin
- Low hypothalamic dopamine level
- Excess sympathetic tone in CNS
- Increased HGP
263
The paradigm dictates that:
- Multiple drugs in combination required to correct the multiple pathophysiological defects
- Treatment should be based on reversal known pathogenic abnormalities and not simply on reducing the A1c
- Therapy must be started early to prevent/slow the progressive beta-cell failure that is already well-established in IGT
264
Effects on:
- Increased HGP
- Decreased glucose uptake in muscles
Antihyperglycemic Effect of Metformin
265
Effect on:
| - Impaired insulin secretion
Antihyperglycemic Effect of Sulfonylurea
266
Effect on:
- Impaired insulin secretion
- Increased HGP
- Decreased glucose uptake in muscles
- Increased lipolysis
Antihyperglycemic Effect of Thiazolidinediones
267
Effect on:
- Impaired insulin secretion
- Increased HGP
- Decreased glucose uptake in muscles
- Increased lipolysis
- Decreased incretin effect
- Increased glucagon secretion
Antihyperglycemic Effect of DPP-4 Inhibitors
268
Effect on:
| - Increased glucose reabsorption in kidneys
Antihyperglycemic Effect of SGLT2 Inhibitor
269
- Activates DA Receptors
- Modulates hypothalamic control of metabolism
- inc insulin sensitivity
Positive
-No hypoglycemia; Dec CVD events
Negative:
- Modest dec in AIc; Dizziness/syncope; Nausea; Fatigue
Dopamine-2 agonists
270
- Inc urinary glucose excretion
Positive
- No hypoglycemia; Weight loss; Improved BP
Negative
- Urogenital infection; Potential volume depletion; Higher LDL
SGLT2 inhibitors
271
- Activates insulin receptor
- Inc peripheral glucose uotake
Positive
- Universally effective; Unlimited efficacy; Dec
microvascular risk
Negative
Hypoglycemia; Weight gain; Mitogenecity; Injectable; Training requirement; Stigma
Insulin
272
Other Considerations: Age
o Reduced life expectancy
o Higher CVD burden
o Reduced GFR
o At risk for adverse events from polypharmacy
o More likely to be compromised from hypoglycemia
o Less ambitious targets
o HbA1c
273
Other Considerations: Weight
```
o Majority of the T2DM patients are overweight/obese
o Intensive lifestyle programs
o Metformin
o GLP-1 receptor agonists
o Bariatric surgery
o Consider LADA in lean patients
```
274
Other Considerations: Sex/Racial/ethnic/genetic difference
o Little is known
o MODY and other monogenic forms of diabetes
o Latinos- more insulin resistance
o East Asians- more beta cell dysfunction
o Gender may drive concerns about adverse effects (eg bone loss from TZDs)
275
Other Considerations: Co-morbidities
```
o Coronary artery disease
Metformin: CVD benefit
Avoid hypoglycemia
SUs and ischemic preconditioning
Piolitazone and dec CVD events
Effects of incretin based Tx
```
o Heart failure
Metformin: May use unless condition is unstable or severe
Avoid TZDs
Effects of incretin based Tx
```
o Chronic Kidney Disease
Increased risk of hypoglycemia
Metformin and lactic acidosis
US: stop @Scr >= 1.5 (1.4 F)
UK: dec dose @GFR
```
276
Summary
- Multiple defects contribute to hyperglycemia in patients
with type 2 DM.
- Addressing these defects early and intensively may lead
to better outcomes.
- Antidiabetic medications may be used as monotherapy or
in combination to achieve individualized glycemic targets
- Knowledge of the advantages and the disadvantages of
the different antidiabetic agents can help us achieve
glycemic targets safely and effectively.
Histology
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