2025 Physiology Exam 3 Flashcards
Lectures 12-16: GI, Reproductive, Nephrology, Bone/Muscle
Regulation of GI Physiology
GI peptides
Nerves
Smooth muscle
Gastrointestinal Peptides/Modulators
GI Hormones
Four steps are required to establish existence of GI hormone:
Physiological release
Effects independent of nervous system
Isolated substance has physiological effect.
Chemical identification and synthesis
Gastrin—Distribution and Release
Know… (for each hormone)
Job
Stimulates HCl from cells in the stomach
Where released
Antrum of Stomach - just before pylorus
Duodenum
The Stimuli
Inhibition - acid reaches set point (Negative Feedback Loop)
Gastrin—Physiological Effects
Cholecystokinin
Job:
Emptying of gallbladder
Contracts gallbladder, relaxes sphincter of Oddi
Pancreatic exocrine
Potent stimulator of enzyme secretion
Weak stimulator of bicarbonate secretion (but can potentiate secretin effects)
exocrine pancreas and gallbladder mucosa
Inhibits gastric emptying
Trophic effects
exocrine pancreas and gallbladder mucosa
CCK—Physiological Effects
Job(s)
CCK—Physiological Effects (Flow Chart)
Secretin
Know
Where Released
Stimuli
Effects
Stops the process of HCl secretion essentially
*** Look into this more past the Gastrin inhibition
Glucose-Dependent Insulinotropic Peptide (GIP)
Stimuli/release
Released from K-cells of duodenum and proximal jejunum
All major foodstuffs—fat must be hydrolyzed.
Oral glucose but not i.v. glucose
Physiological effects
Stimulates insulin release (also called glucose-dependent insulinotrophic peptide—GIP)
Inhibits gastric acid secretion (enterogastrone)
Motilin
Stimuli/release
Released from M-cells of duodenum and proximal jejunum during fasting at 100 min intervals
Release is under neural control (acid and fat can also cause small amounts to be released)
Physiological effects
Stimulates upper GI motility
Accounts for the migrating motility complex, “housekeeping contractions”
Distribution of GI Hormones
Releasers of GI Hormones
Physiological Actions of GI Hormones
Paracrines
Somatostatin (peptide)
Found in gastric/duodenal mucosa and pancreas
Release—stimulated by acid, inhibited by Ach
Inhibits release of all gut hormones
Directly inhibits parietal cell acid secretion
Mediates acid-induced inhibition of gastrin release
Histamine
Gastrin and Ach cause release from cells in stomach
Stimulates acid secretion.
Histamine H2 receptor blockers lower Acid secretion
Cimetidine (Tagamet), Ranitidine (Zantac)
Enteric Nervous System (ENS)
Neural Control of GI Tract
Enteric Nervous System (ENS) Visual
ENS—Myenteric Plexus
ENS—Submucosal Plexus
Parasympathetic Innervation
Excitatory for GI Function
… so you get Rest and Digest
Come out of Cranium and Sacrum
Long Preganglionic Fibers
Short Postganglionic Fibers
Sympathetic Innervation
Inhibitory for GI Function
Come out of Thoracic and Lumber Regions
Short Preganglionic Fibers
Long Postganglionic Fibers
*** Slide wrong with the Long Pre
Neurotransmitters (Neurocrines)
PNS - Parasympathetic
SNS - Sympathetic
*** Know the length for each between Pre and Post ganglions
Sensory Afferent Neurons
Autonomic Nervous System = EFFERENT MOTOR SYSTEM
Afferent is SENSORY
Gastrointestinal Smooth Muscle
Unitary (single-unit) smooth muscle
Slow waves
Spike potentials
Muscle contractions
Unitary (Single Unit) Smooth Muscle
Syncronized Cells acting like Tissue
Gastrointestinal Movements
Peristalsis
Rhythmic segmentation
Tonic contraction
Propulsive Movements - Peristalsis
Stimuli that initiate peristalsis
Distention - orad contraction with downstream receptive relaxation = “Law of the Gut”
Irritation of gut epithelium
Parasympathetic nervous system
Function
Myenteric plexus required
Atropine (blocks Ach receptors) -peristalsis
Congenital absence of plexus - no peristalsis
Motility
Chewing and swallowing
Esophageal motility
Gastric motility
Small intestinal motility
Large intestinal motility
Chewing (Mastication)
Purpose of chewing
Breaks cells—breaks apart indigestible cellulose
Increases surface area—decreases particle size
Mixes food with saliva
Begins digestion of starches (-amylase, lingual lipase)
Lubricates food for swallowing
Swallowing (Deglutination)
Three stages
Voluntary—initiates swallowing process
Pharyngeal—passage of food through pharynx into esophagus
Esophageal—passage of food from pharnyx to stomach
Nervous Control of Esophageal Phase
By Vagus Nerve
Gastric Motility
pH of stomach is ~1
Regulation of Gastric Emptying
Chyme must enter duodenum at proper rate.
pH must be optimal (~7) for enzyme function (pancreas neutralizes the high stomach acid with bicarbonate)
Slow enough for nutrient absorption.
Immediately after meal—emptying does not occur before onset of gastric contractions.
Small Intestinal Motility
Small intestinal motility contributes to digestion and absorption by:
Mixing chyme—With digestive enzymes and other secretions
Circulation of chyme—To achieve optimal exposure to mucosa
Propulsion of chyme—In an aboral direction
Control of Small Intestinal Motility
Whether spike potentials and hence contractions occur depends upon neural and hormonal input.
Nervous factors (PNS—stimulates/SNS—inhibits)
Peristaltic reflex (Law of the Gut)—Mediated by ENS
Intestino-intestinal reflex—Severe distention inhibits bowel Extrinsic nerves
Gastroileal reflex—Meal stimulates. Ileocecal sphincter relaxes, ileal peristalsis increases. (gastrin, CCK, extrinsic nerves, ??).
Ileocecal Junction
Absorption and Storage Function
Job is the absorption of water
Intrinsic Defecation Reflex
Rectal distention initiates afferent signals that spread through myenteric plexus to descending and sigmoid colon, and rectum. This causes contractions that force feces toward anus.
Control of Secretions
Daily Secretion of Intestinal Juices
Mucus Composition—Properties
Buffering - neutralize an acid
Saliva
lipase breaks down fats
Other one???
Majority the Parotid
Functions of Saliva
Lubrication and binding
Solubilizes dry food
Initiates starch digestion
Oral hygiene: Flow of saliva decreases during sleep allowing bacteria to build up in mouth
Functions of Stomach
Short-term storage reservoir
Secretion of intrinsic factor
Chemical and enzymatic digestion is initiated, particularly of proteins (proteins only)
Liquefaction of food
Slowly released into the small intestine for further processing.
Gastric Secretions
Gastric (Oxyntic) Gland
Pyloric Gland
Gastric Acid
Three major functions:
Bacteriostatic
Converts pepsinogen to pepsin
Begins protein digestion (with pepsin)
Pepsinogen
Pepsinogen is an inactive, secreted form of pepsin .
Acid converts pepsinogen to pepsin.
Pepsin (35 kDa) converts more pepsinogen to pepsin.
- Proteolytic enzyme
- Optimal pH 1.8–3.5
- Reversibly inactivated >pH 5.0
- Irreversibly inactivated >pH 7–8
Pepsinogen Secretion
Two signals stimulate secretion of pepsinogen.
Vagal stimulation as mediated by acetylcholine
Direct response to gastric acid
Rennin (Chymosin)
Proteolytic enzyme–Causes milk to curdle in stomach
Milk retained in stomach and released more slowly
Rennin secretion–Maximal first few days after birth. Replaced by secretion of pepsin as major gastric protease
Secreted as inactive proenzyme (prochymosin) that is activated on exposure to acid
Gastric Intrinsic Factor
Regulation of Gastric Secretion
Role of Vagus in Gastric Secretion
Phases of Gastric Secretion
What Is the Gastric Mucosal Barrier?
Integrity of Mucosal Barrier
Pancreas
Youtube this more!!!
Enzymes for Protein Digestion
Enzymes for Carbohydrate Digestion
Why Doesn’t the Pancreas Digest Itself?
Only active once it leaves the Pancreas
Bicarbonate Neutralizes Acid Chyme
Distribution of Secretin
Helps with enzyme Release???
Secretions of Small Intestine
Secretions of Large Intestine
Large intestine also contains crypts of Lieberkühn but there are no villi or enzymes.
Crypts mainly secrete alkaline mucus
Mucus secretion increased by parasympathetic stimulation
Liver Secretion and Gallbladder Emptying
Basis for Digestion—Hydrolysis
Digestion involves the breakdown or hydrolysis (addition of water) of nutrients to smaller molecules that can be absorbed in small intestine.
Carbohydrates—Monosaccharides
Proteins—Small peptides and amino acids
Fats—2-monoglycerides and fatty acids
Types of Digestion
Luminal or cavital digestion:
Occurs in lumen of GI tract
Enzymes from salivary glands, stomach, pancreas
Pancreatic enzymes can do all EXCEPT …
Membrane or contact digestion:
Enzymes on brush border of enterocytes
Digestive Enzymes
Anatomical Basis for Absorption
Sites of Absorption
Digestion of Carbohydrates
Starch digestion:
Begins with a-amylase in saliva (5% digestion in mouth, up to 40% in stomach)
Continues in small intestine with pancreatic amylase
Final digestion occurs at brush border.
Lactose and sucrose—Digestion only occurs at brush border.
Digestion of Proteins
Digestion of Proteins Flow Chart
Assimilation of Lipids– Overall Scheme
Large Lipids to Lymph System through the Lacteals
Chylomicrons—Life Cycle
What Exactly Is Dietary Fiber?
Fluid Entering and Exiting the Gut
Water Movement in Small Intestine
Water moves into or out of gut lumen by diffusion in accordance with osmotic forces.
Hypotonic chyme—Water is absorbed
Hypertonic chyme—Water enters intestine
Chyme is isotonic.
Major Organs of Female Reproductive System
Female Sexual (Menstrual) Cycle
Gonadal tropics = affinity for gonads (FSH and LH)
As FSH Rises = stimulates the egg
… Estradiol rises
at Day 14 LH peaks = ovulation = expelling egg from the ovary
Some woman feel this and its called = blood that is discharged when egg is expelled = mittelschmerz
Follicular Phase
Happens at the Follicular
… a follicle is maturing
Day 4-14 happens at the ovary
FSH is the main component here stimulating the follicle to maturity
Follicle is secreting estrogen and goes back to pituitary to tell it the body doesn’t need any more FSH
Folliculogenesis—Primary Follicle
Primordial follicle matures to Primary follicle
FSH and LH doing this work
Folliculogenesis—Antral Follicle
Folliculogenesis—Vesicular Follicle
Estrogen increases to create the negative feedback loop
LH causes the ovulation
Follicular Phase—Mature Follicle
(Graafian Follicle)
YOUTUBE THIS PORTION
Follicular Phase—Ovulation
Maturation of the Ovum
Maturation of Gametes (sperm and egg) is meiosis
Second part is only completed at fertilization
Spermatogenesis vs. Oogenesis
Know difference between Mitosis and Miesois
Female Sexual Act
Luteal Phase
Estrogen coming out of Egg to lower/Stop FSH at the pituitary
Corpus lutum = progesterone
Day 14 follicle fills with blood?
Hormone Production in Theca Cells
Follicular Phase - stimulated by estrogen, up till ovulation, first 14 days when follicle is being matured
Luteal Phase - after ovulation till menses, the follicle that was there is now filled up fat to form corpus lutum which releases progestogen, progestogen only produced during this phase
Major Ovarian Hormones
Estrogen being produced at the Follicular Stage
Progestogens is produced by the corpus lutum during luteal phase
Regulation—Postovulatory Phase
If no pregancy then the corpus lutum involutes and is called leutolysis??
Regulation—Follicular Phase
Regulation—Preovulatory Phase
? - the 11-2 days? YOUTUBE!!!
Endometrial Cycle and Menstruation
FSH comes from pituatry to tell ovary to produce estrogen/stimulates the follicle to mature
Estrogen goes back to pituatry for negative feedback on FSH (released by maturing follicle)
… also goes to uterus to proliferate cells (basil layer) of uterus (days 5-15), estrogen tells the cells of the uterus to start dividing
Follicular stage of ovary = proliferative stage of uterus
Follicle matures and development of corpus lutum = increase in progesterone
Progetersone causes endothelium to become global Adenomyosis
With no pregnancy, corpus lutum dies (involution of it) = no more estrogen or progesterone
Estrogen tells cervical secretion to be thin and watery
Progesterone tells cervical secretion to be thick and vicious (to block the sperm)
Progesterone works on Breasts
Hormone and Phases Overlay
FSH coming and maturing a follicle = called follicular phase
The follicle secretes estrogen as it matures
… proliferating the cells of the endometrium of uterus
Proliferative phase = Follicular Phase
LH is coming down and causes ovulation, blood enters follicle to release egg
Luteal phase = follicle becomes corpus lutum and secrets progesterone and continues to grow endometrium
If no pregnancy
Corpus albacans = involuted corpus lutum = “dies”
the endometrium thus sluffs off = bleeding and start of menstrual phase
Regulation of Female Sexual Cycle
Anterior Pituitary = 6/7 hormones controlled by Hypothalamus
… GnRH from Hypothalamus to release FSH (causes estrogen release) and LH (high level just before ovulation, caused by the high level of estrogen)
FSH - causes follicular maturation (creating estrogen)
LH - causes ovulation
Ask this slide about the stimulation of FSH? thought estrogen told pituitary to not to produce more FSH
Physiological Effects of Estrogen
Know cell proliferation through protein
Physiological Effects of Progesterone
Breasts increase of lactiferous ducts and alveoli for milk production to feed baby
Puberty, Menarche, Menopause
After 18 yos the “hormones” become pathologic
Menopause is where ovaries become non-responsive to FSH and LH
Male Reproductive System
Spermatogenesis is where the sperm is created
Epididymis matures the sperm “teaches to swim”
Vas deferens carry the sperm to world
Spermatogenesis Location
Interstiutium contains Leydig Cells
Sperm is developed works from outside to inside (see them with the tail)
First stage is Mitosis
Second Stage
Gametes divide by Meiosis
4 haploid cells
Haploid = means half the set of chromosomes
Structure of Mature Spermatozoa
Acrosomes contain lots of enzymes, used to cut thru the outer layer of the egg
Motility
Morphology
Quantity
Maturation of Sperm
Made up of Seman (from seminal vesicles) and Seminal Fluid
Capacitation of the Spermatozoa
Fun Facts About Spermatozoon
Regulation of Spermatogenesis
Sertoli cells are also called nurse cells
Abnormal Spermatogenesis
Cryptochidism = failure for testes to descend
Male Sexual Act
Regulation of Male Sexual Function
Leydig cells stimulated by LH and thus produce Test
Major Sites of Sex Steroid Production
Fun Facts About Testosterone
Role of Testosterone in Fetal Development
Testosterone: Primary and Secondary Sexual Characteristics
Testosterone Production with Age
HPA Control of Testosterone
LH goes to Leydig (testosterones)
FSH to Sertolli (spermatogenesis)
Kidney Functions
last step in synthesis of Vitamin D… important for calcium uptake from gut
Renin - produced by kidney, released to start the release of angiotensin (vasoconstriction) -aldosterone (increased sodium reabsorption) system (RAAS) is a hormone system that controls blood pressure, fluid balance, and electrolyte levels
Filtration, Reabsorption and Secretion
Metabolic Waste Products
Urea (from protein metabolism)
Uric acid (from nucleic acid metabolism)
Creatinine (from muscle metabolism)
Bilirubin (from hemoglobin metabolism)
Secretion, Metabolism, and Excretion of Hormones
Hypocalcemia = Parathyroid Hormone = increase production of D3
Regulation of Erythrocyte Production
Regulation of Acid-Base Balance
Excrete acids (kidneys are the only means of excreting nonvolatile acids)
Regulate body fluid buffers (e.g., bicarbonate, HCO3-)
Increased H+… Body releases more HCO3-… combine to form H2CO3…. splits to form HO2 and CO2 to get rid of the extra hydrogen
Glucose Synthesis
Gluconeogenesis: Kidneys synthesize glucose from precursors (e.g., amino acids) during prolonged fasting
Regulation of Arterial Pressure
Endocrine Organ
Renin-angiotensin system
Prostaglandins
Kallikrein-kinin system
Control of extracellular fluid volume
Regulation of Water and Electrolyte Balance
Sodium and water
Potassium
Hydrogen ions
Calcium, phosphate, magnesium
Basic Mechanisms of Urine Formation
Has fenestrated capillaries
The force behind it is hydrostatic pressure between blood and glomerular
Proximal tubule - the glucose is reabsorbed from the ultrafiltrate
180 g/ml or more of glucose in the blood, the system is saturated, extra is spilling into urea = diabetes (will lead to polyurea)
Anything not needed is Secreted
Excretion =
Filtration − Reabsorption + Secretion
Filtration : Somewhat variable, not selective (except for proteins), averages 20% of renal plasma flow
Reabsorption : Highly variable and selective most electrolytes (e.g., Na+, K+, Cl-) and nutritional substances (e.g., glucose) are almost completely reabsorbed; most waste products (e.g., urea) poorly reabsorbed.
Secretion : Highly variable; important for rapidly excreting some waste products (e.g., H+), foreign substances (including drugs), and toxins
Rates of Filtration, Reabsorption and Excretion
KNOW 180 liters/day each kidney
Renal Plasma Flow, Glomerular Filtration Rate, Tubular Reabsorption and Urine Flow Rate
Whatever we reabsorb goes into the peritubular capillaries
Glomerular Filtration
GFR = 125 mL/min = 180 L/day (KNOW THIS)
Plasma volume is filtered 60 times per day
Glomerular filtrate composition is about the same as plasma, except for large proteins
Filtration fraction (GFR/renal plasma flow) = 0.2 (i.e., 20% of plasma is filtered).
Around capillaries = podocytes = visceral layer
Around the glomurus as a whole = bowman’s capsule = parietal layer
Determinants of Glomerular Filtration Rate
Main pressure is hydrostatic of blood in the capillaries… push the filtration out
Bowman’s Capsule Hydrostatic Pressure (Pb)
Bowman’s Capsule pressure only changes with the disease
Factors Influencing Glomerular Capillary Oncotic Pressure (∏G)
Glomerular Hydrostatic Pressure (PG)
Is the determinant of GFR most subject to physiological control
Factors that influence PG
- Arterial pressure (effect is buffered by autoregulation)
- Afferent arteriolar resistance
- Efferent arteriolar resistance
Hydrostatic pressure is the main determinant of filtration rate
Determinants of Renal
Blood Flow (RBF)
Blood flow is directly proportional to the change in pressure
Blood flow is inversely proportional to the resistance
Renal Blood Flow
High blood flow (~22% of cardiac output)
High blood flow needed for high GFR
Oxygen and nutrients delivered to kidneys normally greatly exceed their metabolic needs.
A large fraction of renal oxygen consumption is related to renal tubular sodium reabsorption
Renal Oxygen Consumption and Sodium Reabsorption
As sodium reabsorption increases so does O2 consumption
Control of GFR and
Renal Blood Flow
Controlled by 2 Factors:
Neurohumoral (hormones)
Local (intrinsic within the kidneys)
Control of GFR and Renal Blood Flow (Sympathetic and Angiotensin II)
KNOW
Control of GFR and Renal Blood Flow (Prostaglandins)
KNOW
Control of GFR and Renal Blood Flow (Endothelial w/ NO2)
Control of GFR and Renal Blood Flow (Endothelin)
Summary of Hormones and RBF
Local Control of GFR and Renal Blood Flow
Autoregulation of GFR and Renal Blood Flow
Myogenic mechanism
Macula densa feedback
(tubuloglomerular feedback)
Angiotensin II (contributes to GFR but
not RBF autoregulation)
Myogenic Mechanism
Macula Densa Feedback (1)
Macula Densa Feedback (2)
Macula Densa Feedback (3)
Regulation of GFR by Ang II
Macula Densa Feedback
Mechanism for GFR Regulation
Calculation of Tubular Reabsorption
KNOW the basic formula:
R= F-E
Calculation of Tubular Secretion
KNOW the basic formula
Reabsorption of Water and Solutes
Glucose Transport Maximum
Glucose lost but reabsorbed
(What part is it lost and reabsorbed in?)
Threshold is 180
Transport Maximum
Glucose has this maximum (180 mg/min?)
Mechanisms of Coupling Water, Chloride, and
Urea Reabsorption with Sodium Reabsorption
Transport Characteristics of
Proximal Tubule
Transport Characteristics of
Thin and Thick Loops of Henle
Early Distal Tubule
Functionally similar in some ways to thick ascending loop***
Not permeable to water (called diluting segment)***
Active reabsorption of Na+, Cl−, K+, Mg++***
~5% of filtered load of NaCl is normally reabsorbed.
Contains macula densa
ADH - released from anterior pituitary will result in water reabsorption in the late distal tubule
Transport Characteristics of Medullary Collecting Ducts
Regulation of Tubular Reabsorption
Hypocalcemia = parathyroid hormone = stimulate osteoclasts to reabsorb the matrix of bone for calcium = tells kidneys to synthesize more D3 (needed to absorb calcium in the small intestine) = tell the kidneys to absorb more calcium from the urine
Determinants of Peritubular Capillary Hydrostatic Pressure
Determinants of Peritubular Capillary Colloid Osmotic Pressure
Aldosterone Actions on Principal Cells
Aldosterone produced in the adrenal cortex
Abnormal Aldosterone Production
Control of Aldosterone Secretion
Angiotensin II Increases Na+ and Water Reabsorption
Effect of Angiotensin II on Peritubular Capillary Dynamics
Angiotensin II Blockade Decreases Na+ Reabsorption and Blood Pressure
Angiotensin Conversion Enzyme = ACE Inhibitor = decrease the amount of vasoconstriction by not enough of the enzyme to convert AT I to AT II
Antidiuretic Hormone (ADH)
Osmolarity decreases because more fluid is reabsorb = decrease extracellular osmolarity
Antidiuretic Hormone
Feedback Control of Extracellular Fluid Osmolarity by ADH
More fluid in the blood stream = decrease the osmolarity
Control of Ca++ by Parathyroid Hormone
Sympathetic Nervous System Increases Na+ Reabsorption
Directly stimulates Na+ reabsorption
Stimulates renin release
Decreases GFR and renal blood flow (only a high levels of sympathetic
stimulation)
Increased Arterial Pressure Decreases Na+ Reabsorption (Pressure Natriuresis)
Control of Extracellular Osmolarity (NaCl Concentration)
Concentration and Dilution of the Urine
Want a high dilute if dehydrated
Want a Dilute urine when over hydrated
Formation of a Dilute Urine
ADH works on Distal and Collecting tubules
Formation of a Concentrated Urine When Antidiuretic Hormone (ADH) is Elevated
The Vasa Recta Preserve Hyperosmolarity of Renal Medulla
Disorders of Urine Concentrating Ability
Stimuli for ADH Secretion
Factors That Decrease ADH Secretion
Blood is dilute, decrease the amount of water going to blood to further dilute
Body Fluid Regulation
Extracellular = interstitial and blood
Intracellular = in the cell
Must be equal
Balance Concept Electrolytes
Fluid Balance (mL/day)
70 kg Adult
Want that 2300…
Control of Body Fluid Distribution
Principles of Osmotic Equilibria
Effects of Solutions on Cell Volume
Osmolarity of a 5% glucose solution
Osmolarity of a 3% NaCl Solution
Determinants of Capillary Filtration
Lymphatics take away that 10% in interstitial
Lymphatic failure = Edema
Low Tissue Compliance and Negative Interstitial Fluid Hydrostatic Pressure
Increased Lymph Flow
Normal Potassium Intake, Distribution,
and Output from the Body
Control of Cortical Collecting Tubule (Principal Cells) K+ Secretion
Increased K+ Intake Increases
K+ Excretion
Effect of Increased Sodium Intake on Potassium Excretion
Acidosis Decreases Cell K+
Can cause depletion
Mechanisms of Hydrogen Ion Regulation
Buffer Systems in the Body
Bicarbonate Buffer System
Bicarbonate Buffer System
Respiratory Regulation of Acid-Base Balance
Renal Regulation of Acid-Base Balance
Regulation of H+ Secretion
Phosphate as a Tubular Fluid Buffer
Two Types of Bone Formation
Endochondral ossification
Intramembranous ossification
Ossification is the conversion of soft tissue into bone, whether normal or abnormal
(Long bone occurs at the epiphyseal plate)
Growth Hormone and ossifciaition
Post Puberty = acromegalia = bones grow in width
Pre Puberty = gigantism = bones grow in length
Endochondral Ossification Overview
Cartilage model serves as the precursor of the bone…
Examples of this are the bones that bear weight.
Ossification is another word for osteogenesis and sometimes used for when bone is becoming calcified.
Endochondral Ossification Process
Begin with mesenchymal cells as well but need to make a cartilage matrix first.
Mesenchymal cells under the influence of fibroblastic growth factors and bone morphogenic proteins, the mesenchymal cells express type II collagen at first.
The mesenchymal cells then differentiate into chondroblasts, which produce the cartilage matrix.
The chondroblasts contribute to the growth of the width of the bone.
Interstitial growth attributes to bones growth in length.
The matrix model is hyaline cartilage.
The most outer portion becomes the periosteum, which was made by osteoblasts.
This layer of the bone is very sensitive to pain.
A distinctive cuff of bone occurs in the diaphyseal portions called the bony collar.
Now the chondrocytes begin to hypertrophy and begin synthesizing alkaline phosphatase.
The surrounding matrix goes through calcification.
Intramembranous Ossification
Bone formed by differentiation of mesenchymal cells into osteoblasts… lay down the osteoid to form bone
Examples of this type of bone are the flat bones of the skull, face, and clavicle.
Intramembranous ossification is seen around the 8th week of gestation.
As the osteoblasts secrete collagen (mostly type I), bone sialoproteins, and osteocalcin.
Collagen requires Ascorbic acid (Vitamin C) as a cofactor for the essential enzyme Lysyl hydroxylase.
This collagen then goes through a process called ossification which is calcifying the collagen.
Upon calcification the osteoblasts become osteocytes within the canaliculi and eventually the lacunae.
During this developmental phase the bone is also forming its own blood vessels (angiogenesis).
(Powerpoint 1, slide 14 has an animation)
KNOW WHERE RESERVE CALCIUM AND VITAMIN D COMES FROM
Ossification
Hyaline cartilage: Type I collagen with mucopolysaccharide (organic glue)
Hydroxyapatite crystals then precipitate onto the collagen
Calcium and phosphate (PO4) salt then get deposited within the crystals to harden or ossify the bone
The Osteoblasts
Like its close relatives, the fibroblast and the chondroblast, theosteoblastis a versatile secretory cell that retains the ability to divide. It secretes bothtype I collagen(which constitutes 90% of the protein in bone) andbone matrix proteins (BMPs), which constitute the initial unmineralized bone, orosteoid.
The bone matrix proteins produced by the osteoblast include calcium-binding proteins such as osteocalcin and osteonectin; as well as multi-adhesive glycoproteins such as bone sialoproteins I and II, osteopontin, various proteoglycans, and alkaline phosphatase (ALP).
Osteocalcin’s function is to bond hydroxyapatite to collagen. Vitamin-K helps osteocalcin do it’s bone bonding work.
The collagen is then calcified. 70% of bone is inorganic salts, in dentin or cementum it is only 45%.
Calcium is what causes ossification
Osteocytes
The Osteoblasts becoming Osteocytes
Osteoblasts become Osteocytes
The Osteoclasts
Osteoclasts resorb bone tissue by releasing protons and lysosomal hydrolases into the constricted microenvironment of the extracellular space.
Some, if not most, of the vesicles in theosteoclastare lysosomes. Their contents are released into the extracellular space in the clefts between the cytoplasmic processes of the ruffled border, a clear example oflysosomal enzymesfunctioning outside the cell. Once liberated, these hydrolytic enzymes, which includecathepsin K(a cysteine protease) andmatrix metalloproteinases, degrade collagen and other proteins of the bone matrix.
Regulation of osteoblasts and osteoclasts (calcium regulation)
Bone is regulated by mechanical forces but also, if not more so, by hormones.
The two primary hormones are parathyroid hormone (PTH) from the parathyroid glands embedded in the posterior thyroid. The other is calcitonin which is released from C-cells (aka Parafollicular cell) in the thyroid.
PTHacts on the bone toraise blood calcium levelsto normal. Bone is the bodies reservoir for calcium.
Calcitoninacts to lower blood calcium levels to normal.
During child development and puberty the hormone somatotropin or growth hormone (GH) is a crucial hormone for the growth of bone and epiphyseal cartilage (growth plates).
It acts directly on osteoprogenitor cells, stimulating them to divide and differentiate. Chondrocytes in epiphyseal growth plates are regulated by insulin-like growth factor I (IGF-I), which is primarily produced by the liver in response to GH.
Hypocalcemia = osteoClast activation = PTH (hypercalcemic hormone/looking to raise blood calcium)
Hypercalcemia = osteoBlast activation = Calcitonin (hypocalcemic hormone/looking to lower blood calcium)
Regulation of osteoblasts and osteoclasts (calcium regulation): Parathyroid Hormone
PTH is released when calcium sensing receptors in the parathyroid gland sense a decrease in serum calcium.
In the plasma…40% of the calcium is protein bound and 60% is not and thus is filterable by the kidneys.
Only free, ionized calcium is biologically active.
PTH is an overall calcium regulator. When secreted it will also make the kidneys stop secreting calcium and to make more Vitamin D. Vitamin D is essential for calcium absorption into the body.
Hypovitaminosis D can result in hyperparathyroidism
PTH also tells the intestines to absorb more calcium indirectly by stimulating Vit D3 production in the kidney.
Stimulate osetoclasts to reabsorb bone
Tells kidneys to increase intake of calcium
Tells kidneys to produce more Vitamin D
PTH inhibits renal phosphate reabsorption from the proximal tubule, which increases phosphate excretion. Phosphate and bone have inverse relationships in the body, as one increases the other decreases and vice versa.
The renal reabsorption of calcium occurs in the distal tubules of the nephron
Calcium-Phosphorus Relationship
Parathyroid Hormone Osteoclast Activation
Parathyroid hormone(PTH)binds to receptors on osteoblasts, causing them to form receptor activator for nuclear factor kappa-B ligand(RANKL) and to release macrophage-colony stimulating factor(M-CSF).
RANKL binds to RANK while M-CSF binds to its receptors on preosteoclast cells, causing them to differentiate into mature osteoclasts.
PTH also decreases production of osteoprotegerin(OPG),which inhibits differentiation of preosteoclasts into mature osteoclasts by binding to RANKL and preventing it from interacting with its receptor on preosteoclasts.
Regulation of osteoblasts and osteoclasts (calcium regulation): Calcitonin
Acts primarily to inhibit bone resorption. Does this by inhibiting the osteoclasts.
Excreted by the C-cells (Parafollicular cells) in the thyroid in reaction to hypercalcemia.
The more prolonged the hypercalcemia it decreases the formation of new osteoclasts.
Minor effect on the calcium handling by the kidney and intestines.
Smooth Muscle Physiology
Multi-Unit Smooth Muscle
Present in iris, ciliary bodies, and vas deferens.
Behave as separate motor unties.
Has little or no electrical coupling between cells.
Is densely innervated; contraction is controlled by neural innervation.
Unitary (Single-unit) Smooth Muscle
Is the most common type and is present in the uterus, GI tract, ureter, and bladder.
Is spontaneously active (exhibits slow waves) and exhibits “pacemaker” activity, which is modulated by hormones and neurotransmitters.
Has a high degree of electrical coupling between cells.
Vascular Smooth Muscles
Has both multi-unit and single-unit smooth muscle.
Smooth Muscle Physiology Activation
The is NO troponin; instead Ca2+ regulates myosin on the thick filaments.
Average duration of action potential is 10 msec vs skeletal muscles 1 msec.
Molecular basis for contraction: Ca2+-calmodulin increases myosin light-chain kinase.
Smooth Muscle Physiology: Steps in Contraction
Depolarization occurs: Opens voltage-gated Ca2+ channels and Ca2+ flows into the cell.
Hormones and neurotransmitters may open ligand-gated Ca2+ channels in the cell membrane. They also directly release Ca2+ from the sarcoplasmic reticulum through inositol 1,4,5-triphosphate-gated Ca2+ channels.
This increase in calcium binds to calmodulin.
This complex binds to and activates myosin light-chain kinase.
This myosin then phosphorylates myosin and allows it to bind to actin.
The amount of tension produced is proportional to the intracellular Ca2+ concentration.
A decrease in intracellular Ca2+ produces relaxation.
Skeletal Muscle: End-Motor Plate
Skeletal Muscle: End-Motor Plate
Powerpoint 1, slide 41 has great animation
Steps in Excitation-Contraction Coupling in Skeletal Muscle
AP depolarizes the sarcolemma (muscle cells membrane) which depolarizes the T tubules
This changes a dihydropyridine receptor’s shape, which opens Ca2+ release channels (ryanodine receptors) in the nearby sarcoplasmic reticulum.
The SR is a membrane-bound structure that stores calcium.
Calcium floods into the intracellular space; this calcium binds to troponin C on the thin filaments.
This allows tropomyosin to move out of the way so myosin can attach to actin.
At first, myosin is attached to actin…adenosine triphosphate (ATP) attaches to the myosin which DETACHES the myosin from the actin.
Myosin attaches to a new site on actin, which constitutes the power (force-generating) stroke. ADP is then released, returning myosin to its rigor state.
This cycle repeats as long as Ca2+ is bound to troponin C. Each power-stroke or cross-bridge cycle “walks” the myosin further along the actin filament.
Relaxation occurs when calcium goes back into the sarcoplasmic reticulum via Ca2+ -ATPase channels
Sarcomere: The Functional Unit of Muscle
Neuromuscular Junction
Neuromuscular Junction (2)
Synaptic Cleft is more chemical than physical
Drug Effects on End Plate Potential: Inhibitors
Drug Effects on End Plate Potential: Stimulants
Excitation-Contraction Coupling
EC Coupling—Comparison
Cellular Organization
The Sarcomere
“Walk-Along” Theory
“Walk-Along” Theory
Tension as a Function of Sarcomere Length
Isometric = tension increases = muscle fibers stay same
(Pushing against a wall)
Isotonic = tension remains the same = muscle fibers shorten
(DB Curl)
Isometric and Isotonic Contractions
Types of Skeletal Muscle
Motor Unit
Muscle Remodeling—Growth
Muscle Remodeling—Atrophy
Types of Smooth Muscle
Special Features of Smooth Muscle
Smooth Muscle
Neuromuscular Junction
Have varicosities not motor neurons
Smooth Muscle–EC Coupling
The troponin complex is absent. (Calmodulin is very similar in structure.)
Control of SM Is Diverse
