Exam 7 Flashcards
What are the actions of insulin?
STOPS:
- Gluconeogenesis
- Glycogenolysis
- Lipolysis
- Ketogenesis
- Proteolysis
Go:
-Glucose uptake in muscle
-Glycolysis
-Glycogen synthesis
-Protein Synthesis
Uptake of Ions specially K+, PO4
How does Insulin affect carbohydrates metabolism?
Decrease blood glucose by helping glucose leave blood and limiting the raise in blood glucose
Increases glucose transport and adipose into muscle
Promotes gycogen formation in liver and muscle
Aids GLUCOKINASE: phosphorylation of glucose
Inhibits gluconeogenesis and glycogenolysis
Actions of Insulin in Lipids metabolism
Overall, Inhibits mobilization and oxidation of FA
Inhibits Ketogenesis
Ketogenesis: breakdown of FA in liver, during fasting produces Ketoacidosis.
Promotes FFA storage as Triglycerides. LIPOPROTEIN LIPASE-Storage of triglycerides
Inhibits uptake of FFA in muscles, in favor of glucose uptake in muscles
Inhibits Lipolysis: HORMONE SENSITIVE LIPASE
The effects of protein are overall cataolic or anarobic?
ANABOLIC
Decreases blood AA
Increases AA and protein uptake by tissues
Increases protein synthesis
Inhibits protein degradation
What are the other actions of insulin?
Increases activity of Na/K ATPase pump = Uptake of K+ into cells
Promotes Phosphate, Mg++ uptake into cells
Decreases appatite via the SATIETY CENTER in HYPOTHALAMUS
What happens when there is an excess of insulin in the blood/body?
Causes HYPOGLACEMIA
Cortisol release is stimulated to increase appetite
What or how does Insulin Resistance occur?
When blood insulin remains high (over-produced) and the cells fail to respond normally. This is a defensive mechanism during illness to protect brain’s glucose supply.
Resistance can occur due to receptors alterations, decreased affinity or number of receptors.
Post-receptor changes in the intracellular action of insulin.
How do Hormones cause insulin resistance?
Cortisol, GH, Thyroid hormones, Epinephrine, Estrogen/Progesterone:
Epi: antagonizes insulin and stimulates the release of glucagon, thus increasing blood glucose
Progesterone: during pregnancy favors the transfer of nutrients to fetus.
How does obesity cause insulin resistance?
Type II diabetes
Impared insulin signaling
Decrease GLUT4 expression in adipose and muscle tissue or it can be normal, but Decrease Transport of clucose occurs due to TRANSLOCATION/DOCKING of GLUT4 into plasma membrane.
How does liver or kidney failure cause insulin resistance?
Sepsis and Insulin Antibodies?
Defect in kidney results in defect of Post reception pathway and possible decrease in GLUT4 in skeletal muscle.
Sepsis: Insulin signaling defect with infection. Stress causes hypoglacemia, release of glucose.
Insulin antibodies affect the normal effects of insulin
Characteristics of Diabetes Mellitus type 1 and type 2
Type 1: insulin defficiency due to destruction of pancreatic Beta cells, autoimmune issue usually
Type 2: Insulin resistance: can be associated with down-regulation of insulin receptors in muscle and adipose tissues or issues with insulin signaling.
What is Insulinoma?
Excessive production of insulin by Beta cells in the pancreas
What are the results of lack of insulin or lack of insulin action?
Hyperglacemia due to decrease in hepatic output: Type 2 diabetes and decreased glucose uptake by cells. Cell starvation
Increase in glycogenic AAs liver keeps making it
Increase glucagon release because carbohydrate ingestion does not suppress it
Blood Hyperosmolality: glucose draws water and doesn’t leave
Osmotic diuresis in kedney: beyond threshold ~300 mOsm/L, glucose excess in urine and water follows.
Hyperlipidemia: Increased oxydation of fat, Fat accumulation in liver, Increase Ketoacidosis.
Increase glycolysis and Increase Lipid uptake
Peripheral tissue catabolism: Muscle wasting and weight loss
Increase gluconeogenesis and Decrease AA uptake by cells
Glucagon
What cells secret it?
What stimulates its release?
What inhibits its release?
Secreted by alpha cells in the pancreas
Synthesized as preproglucagon untils its release
Sequence is identical in all species
Stimulation: Hypoglacemia, Protein, and AA intake/ingestion
Fasting, Stress (specially infection), Intense excercise, CCK (CHOLECYTOKININ is released when protein and fat is ingested)
Inhibition: Glucose, Insulin, SOMATOSTATIN
Actions of Glucagon
Pathophysiology
G-protein/cAMP
Opposite of Insulin actions
Mobilizes energy, Increases glycogenolysis, gluconeogenesis, lipolysis, ketoacid formation
Little to no effect on glucose utilization by peripheral tissues.
Pathophysiology
Tumor of Alpha cells Glucagonoma
Results in Diabetes Mellitus and Necrolytic Migratory Erythma (blisters, swelling and pressure in areas of body)
Hyperglucagonemia/diabetes mellitus with infection
Glucagon:Insulin ratio increases
Where is Somatostatin secreted?
Delta cells of pancreas, Hypothalamus, and GI cells
SS-28: GI tract
SS-14: Pancreas and Hypothalamus
Stimulated by all nutrients
Inhibits Insulin, Glucagon, GI Hormones, GI motility, enzymes, gastric acid secretion.
AAs are needed for liver to perform gluconeogenesis
Adipose tissue as an Endocrine organ
Leptin and Adiponectin
Leptin
Inhibits appetite by inhibiting Neuropeptide Y
Increase BMR
Leptin resistance may contribute to Obesity
Adinonectin
Improves insulin sensitivity
High adinonectin = low risk of Type II diabetes
Low adinonectin = obesity and diabetes in cats by increasing TYROSINE PHOSPHORYLATION in insulin receptor in skeletal muscle
What are the processes and regulatory systems that depend on calcium and phosphorus?
Vitamin D
Parathyroid Hormone
Calcitonin
Neurotransmission, learning, memory, muscle contraction, mitosis, mobility, secretion, fertilization, blood clotting, structure of bones and teeth.
Intestine: absorbs
Kidney: Reabsorption
Skeleton: Reservoir
Skin: Makes it
Liver: Makes it
What is they biologically active form of calcium?
Where is the highest concentration?
What cells are involved in calcium homeostasis?
Highest: Extracellular
50% Ionidized (active) free form. The rest bound in albumin, complex anions.
10% complexed in other forms
Phosphate bicarbonate
Intracellular: lowest concentration
Cytosolic Ca++ can be increased as needed- fine balance control. Concentration depends on membrane permeability and motility. Intracellular storage.
The endocrine cell receptors are involved in Ca++ homeostasis
Endoplasmatic Reticulum: Calcium Channels, Na/Ca exchanger.
Hypercalcemia & Hypocalcemia
What causes alterations in the forms of Calcium in plasma?
Increase in plasma Ca concentration
Constipation, polyuria, polydipsia, lethargy, coma, death.
Hypocalcemia: decrease in plasma Ca++.
Twitching, cramping of skeletal muscle. Seizures, sensory and motor neurons highly excitable due to Lower threshold for excitation. Lower ECF Ca++
Numbness/tingling (paresthesia) seizures.
- Changes in plasma protein concentration
- Changes in complex anion concentration
- Acid-base disturbances
- Changes in HCO3 cuases changes in Calcium
- Lactation, Renal failure, Vitamin D disorders.
Acedemia and Alkalemia
What is the difference in Albumin-bound-calcium in each state?
Acedemia: More H in the blood
- High concentration of Ionized Ca++ (free form), so less is bound to Albumin
Alkalemia: Less H in the blood
-Low concentration of Ionized Ca++ bound to Albumin.
Calcium Homeostesis
What role do kidneys, intestines, parathyroid, and vitamin D have on this?
Bone is constantly remodeled to that Ca can be released into the blood or absorbed from blood.
Intestine absorbs Ca, the amount is regulated by Vitamin D.
Kidneys reabsorbed Ca and this is regulated by the PTH calcitonin
Calcitonin
Calcitonin works to control calcium and potassium levels. It does this by inhibiting the activity of the osteoclasts, the cells that break down bone. When the osteoclasts break down bone tissue, the calcium enters the bloodstream.
Osteoclast: bone reabsorbing cells Clast:collapsing
Osteoblast: bone forming cells Blast: building
Phosphate metabolism
Components of ATP, DNA, Lipids, Cofactors, RNA, bone
It regulated through urinary secretion
It is stored in Muscle
The percentage absorbed from diet is fairly constant
Balances many Cations and it is important for buffering and Magnesium absorption.
Magnesium metabolism
Necessary for Neuromuscular transmission
Cofactor in enzyme reactions
Dietary Mg absorbed by gut is enhanced by Vitamin D
Excreted in Urine
Parathyroid Hormone
Chief Cells and Oxyphil Cells
- Regulates plasma Ca and Phosphate
- PTH stimulates bone resorption. Increases kidney reabsoprtion Ca and Phosphate Excretion in Urine.
- P receptor acts when high Ca is present in blood, then degradation of PTH ganules and inhibits its release (PTH)
Phosphate high in blood, then PTH secretion Increases via P receptor
PTH also stimulates synthesis of Vitamin D
Chief cells:
Oxyphil cells: not present until puberty and decrease with aging
Stimulation and Inhibition of PTH
Stimulation: Decreased calcium (Bone resorption and calcium reabsorption in Kidney)
Increased Blood phosphate (Phosphate excretion in urine)
Decreased Mag
Inhitition: Vitamin D negative feedback (calcium absorption in SI) Decrease PTH release
Increased blood calcium
Action of PTH
Receptor Pathway
Binds to plasma membrane receptors and activates G-proteins/cAMP pathway
Bone: Increases bone resorption to relase Ca and Phosphate into blood
Kidney: Stimulates calcium reabsorption DCT, while it inhibits Phosphate reabsorption in PCT causing excretion of Phosphate
Increases Mg reabsorption and stimulates synthesis of vitamin D in kidneys
Intestine: Increases Ca absoprtion via vitamin D
Hyper and Hypoparathyrodism
Hyperparathyroidism: Tumors or hyperplasia
Primary Form
Cs: Increased PTH and hypercalcemia, Hypophosphotemia, Renal calculi, Bone pain/Fractions
Secondary Form
Hypocalcemia, Increased Phosphate in blood, increases in PTH, may result from renal failure or increased dietary phosphate
Decreased blood Ca = Increased PTH
Hypothyroidism
Caused by accidental removal of gland, Autoimmune destruction, Idopathic
Cs: Decreaed PTH, Hypocalcemia, Hyperphosphatemia
Calcitonin synthesis and Role
Parafollicular cells of Thyroid Gland synthesize calcitonin
Decreases blood Ca and Phosphate by:
- Inhibiting bone resorption
- Increases urinary P excretion
- Inhibits renal reabsorption of Ca
Stimulation:
Increase blood Ca
Vitamin D (via feedback)
Ingested food, Ca absorbed in SI, so don’t need to release it or reabsorb it from kidney
Role and Vitamin D synthesis
Required for bone formation and Increases Ca absorption from GI tract
Hormone synthesized and Vitamin from diet
Skin: synthesizes precursor 7-dehydrocholesterol
After absorption from GIT goes to liver and it is converted to 25-hydroxycholecalciferol
Kidney: most converted to 1,25-dihydrohycholecalciferol
Intermediate and active forms circulate bound to protein carriers
Vitamin D actions
Fat-Soluble, so it can be stored in adipose and liver
-Toxicity results in hypercalcemia, renal failure, elevated phosphate
Metabolism: excreted in bile
Most Actions occur in the intestine
- Stimulate Ca absorption via calbindin
- Stimulates Mg absorption and phosphate absorption
Weakly stimulates Ca and P reabsorption in Kidney
Vitamin D and Ca absorption Intestines
Effects of vitamin D deficiency
Active
-Intake Low, via transcellular process (dominates)
Passive
(no assistance needed)
-Intake High, paracellular (dominates)
Acts through cytosolic receptor and increas es production of CALBINDIN
Calbindin binds Ca inside the cells and fascilitates transport to bsolateral membrane
Other effects of Vitamin D
Stimulates bone resorption in the prescence of PTH
Increases Ca transport and uptake by SR in skeletal muscle cells
Decreases PTH synthesis feedback effect
Deficiency = muscle weakness, abnormal contractions, Ricketts in young, Ostomalecia in older animals, Cardiac disfunction
Melatonin and Eicosanoids
What is the major role of melatonin?
Where is it produced and synthesized from?
What supresses melatonin release?
where is the photic information transmitted and processed?
Major role in sleep and wakefullness
Produced by the Pineal Gland and synthesized from Tryptophan (N-acetyl-5methoxytryptamine) with SEROTONIN as the intermediate.
Blue light supresses melatonin release.
Photic information from the RETINA is processed/recieved in the HYPOTHALAMUS and SNC via Supra-Chiasmatic Nucleus, then to Pineal Gland
Regulation of Melatonin
What stimulates and inhibits secretion of melatonin?
What is is related to?
Stimulated by darkness.
It is related to the length of the night
Retinal photoreceptors release norepinephrine which activates beta-adrenergic receptors in the pineal gland. Seratonin is converted into Melatonin by darkness stimulation
Inhibited by light
Retinal photoreceptors become hyperpolrized, which inhibits norepinephrine release.
Blind people can still have ligth-induced sdupression of melatonin
Circadian Rythm of melatonin secretion
What is it controlled by?
When does secretion begins and peaks?
Controlled by endogenous pacemaker in the supra-chiasmatic nucleus
Environmental lightining alters timing of the circadian rythm
- Day-night cycles can modify the rythm
- Brief pulses of light can supress release of melatonin
Secretion usually begins at DUSK and pekas between 2-4 am
Shifts in melatonin secretion after flights across time zones and in night-shift workers
Tryptophan-seratoning-melatonin
Actions of Melatonin and Receptors
Activates Receptors MT1 & MT2
Regulates/Affects
- Sleep
- Circadian rythm
- Mood
- Sexual maturation and reproduction
- May have anti-inflamatory effects on immune system
- May have beneficial effects on cancer (removing pineal gland enhances tumor growth)
- Aging (decreases with age) may reduce cell damage by reducing free radicals
Biological functions and SAD
SAD: Seasonal affective disorder
- Abnormal circadian rythms involved in mood disorders
- Bright light therapy can decrease SAD
Sexual maturation and reproduction
Hours of light/darkness associated with reproductive activity
May affect sex steroid synthesis and modulate ovarian function
Horses seasonal estrous cycle. Spring decreases melatonin, which allows GnRH to increase and stimulate progesterone synthesis. Supressing melatonin in mares with light, babies born in January
Decrease melatonin in puberty leads to increase in GnRH
How is Melatonin used in VetMed?
Treatment for Alopecia X in dogs
-May decrease GnRH, which decreases FSH/LH effects on adrenal androgen precursors
Tx for anxiety and seizure activity
Short-term side effects are minimal
-Sedation and incoordination
Eicosanoids
What are the two major pathways for synthesis?
Group of signaling molecules synthesized by oxidation of 20-carbon essential fatty acids (EFA)
Arachidonic acid and Eicosapentaenoic acid
- Omega-3 EFAs from Eicosapentaenoic acid LESS-inflamatory
- Omega-6 from arachidonic acid PRO-inflamatory
Omega-3 diet reduces inflamation
Balance between each type determines actions
Derivation of Eicosanoids
Omega-3 FAs: yields eicosapentanoic acid (5 double bonds) # 3,5
Omega-6 FAs: yields arachidionic acid (4 double bonds) # 2,4
- Prostanoids with 2 double bonds
- Leukotrienes with 4 bonds
Nomenclature for Eicosanoids
- 2 letter abbreviation = PG
- One A-C sequence letter = PGE
- Subscript indicating the # of double bonds = PGE2
Prostaglandins A-I differ in subtituents on the cyclopentane ring
- PGAs are alpha and beta-unsaturated ketones
- PGEs are Beta-hydroxyl ketones
- PGFs are 1,3-diols
EPA Cascade (eicosapentaenoic acid)
Formed from Omega-3 EFAs
Forms mostly prostanoids
Major function is to dampen inflammatory effects of arachidonic acid prostanoids
Less inflamatory pathway
Arachidonic acid (AA) Cascade
Formed from Omega-6 FAs
- Prostanoids: Prostaglandins (PG), Prostacyclins (PGI), Thromboxanes (TX), Major effects
- Leukotrienes (LT)
- Lipoxins (LX): stimulate inflammatory responses, modulate pain and fever, reproductive functions, INHIBIT GASTRIC ACID SECRETION (usually paracrine local action), Blood pressure regulation, Platelet activation/inhibition
Synthesis of Arachidonic Acid
Dietary precursors:
- Linoleic Acid (18 carbon EFA)
- Gamma linoleic acid
- Cats can’t convert linoleic acid to arachidonic acid due to low Delta-6-desaturase enzyme
Phospholipase A releases arachidonic acid from phospholipids in cell membrane
-Arachnidonic acid is oxydated by
*Cyclooxygenase (COX1, COX2) to make prostanoids
*Lipooxygenase (5LOX) to make leukotrienes
Major actions of prostanoids derived from Arachidonic Acid
-Local hormones with autocrine or paracrine action. Short half-life (seconds to minutes). Mediated by specific receptors. Mediate inflammation (except lipoxins)
PGE2,Smooth muscle contraction, bronchoconstriction, heat, fever.
PGI2vasodilation, inhibits platelet aggregation.
TAX2 Vasoconstriction, stimulates platelet aggregation.
Inhibiting prostanoid formation
NSAIDs
Non-steriodal anti-inflammatory drugs.
- Decrease inflammation, redness, swealling, heat.
- Inhibit COX1, COX2: Aspirin, Carprofen, Fluxinin, Phenylbutazone, Ibuprofen, naproxen
- NSAIDs that inhibit only COX2: Less side effects, Firocoxib, deracoxib, Melaxicam, Piroxicam, Celecoxib.
Reproductive events after fertilization
First Trimester:
- Migration of primordial germ cells from yolk sac
- Sex cords develop in gonad, paramesonephric ducts develop
- Sex evident from structures
- Begening of development of male ducts and testes or Development of female ducts and ovaries
Second Trimester:
- Development of male ducts and testes or Development of female ducts and ovaries
- Formation of braod ligament
Bull and Ram 6. Testicular descent
Third trimester:
- Testicular descent
Boar & human earlier
Colt Later in the 3rd trimester
What is an Embryo?
What is a Fetus?
Embryo: An organis in the early stages of development
Placentation has not yet taken place
Generally this embryo has not acquired an anatomical form that is readily recognizable in apperance as member of a specific species
Fetus: Potential offspring within the uterus that is generally recognizable as a member of a given species
Marked by development of placentation and organogenesis
What are the Primary Embryonic Layers? Embryology
How does the embryo start?
The embryo starts as a mass of cells that eventually form cell layers and it will differentiate into embryo and proper and placenta
Endoderm Digestive system, lungs, endocrine system
Mesoderm Muscle, skeleton, Cardiovascular, Reproductive System
- Gonads (testicles and ovaries)
- Uterus, Cervix, cranial vagina
- Epididymis, ductus deferencs
- Accessory sex glands
Ectoderm Nervous system, Skin, Hair.
Reproductive tract:
- Vagina and Vestibule
- Penis and clitoris
Embryology and placentation
What is blastocyst?
What is the Inner Cell Mass (ICM) and Trophoblast?
What do the Trophoblastic cells eventually give rise to?
What is the Chorion?
The embryo is called blasstocyst when a cavity is recognazible
The ICM and trophoblast corresponds to the two distinct cellular populations that result from the embryo becoming partitioned.
Tight junctions: found in the outer cells
Gap Junctions: found in the inner cells
Trophoblast = Chorion
The Chorion: will become the fetal component of the placenta
What are the four steps to be achieved before the embryo can attach to the uterus?
What is SYNGAMY?
What is an ootid?
What is a Zygote?
What is a Blastomere?
What is a Morula?
What is a Blastocyst?
What is a hatching Blastocyst?
- Development within the confines of ZONA PELLUCIDA
- Hatching of the BLASTOCYST from zona pellucida
- Maternal recognition of pregnancy
- Formation of extraembryonic membranes
Syngamy: fusion of the male and female PRONUCLEI
OOTID: cell name when a female and male pronuclei can be observed
-It is one of the largest cells and has subsequent cell divisions within the cinfines of the zona pellucida
Zygote: Single-celled embryo that undergoes mitotic divisions called CLEAVAGE DIVISIONS
First cleavage division: generates two-celled embryo, which are called Blastomeres
Morula: After the eight-celled embryo stage the ball of cells fromed is called Morula
Early blastocyst: after the morula continues to divide a blastocyst is formed.
Blastocyst consists of:
- ICM: inner cell mass
- Blastocoele: cavity
- Trophoblast: single layer of cells
Hatching blastocyst: grows in zona pellucida and free floats within the uterus
What do the extraembryonic of the preattachment embryo consists of ?
- Yolk Sac: from primitive endoderm. Feeds the embryo until placentation
- Chorion: from Trophoblast, primitive endoderm, and mesoderm
- Amnion: filled with fluid and serves to hydrolically protect the embryo
- Allantois: comes out of the hindgut joins and fuses with chorion to become Allanto-Chorion
1. Trophoblast cell is the placenta
2. Blastocoel
3. Inner cell mass: become fetus
Origen of the Pituitary Gland
Posterior Lobe: Neurohypophysis
- Contains axons and nerve terminals of neurons from hypothalamus
- Formed from a diverticulum from floor of brain = infundibulum
Anterior lobe: Stomodeal Ectoderm Adrenohypophysis
- Tissue from the root of the mouth
- Glandular epethilieal cells produce GLYCOPROTEIN hormones
- Formed from an evagination from the oral cavity = Rathke’s Pouch
What happens to Rathke’s pouch?
Stalk of Rathke’s pouch regresses and separates from Stomodeal Ectoderm
-It becomes closely associated with cells of INFUNDIBULUM
Adrenohypophysis loses attachment to mouth
What hormones are released by the anterior and posterior pituitary gland?
Where are posterior pituitary hormones released into?
Hormones released into circulation require a larger exogenous amount to be effective than locally released hormones
Anterior:
- ACTH: adrenocorticotropic hormone
- TSH Thyroid stimulating hormone
- Gonadotropins FSH, LH
- GH Growth Hormone
- Prolactin PRL
Posterior: Deposited directly into circulation, Hypothalamic hypophyseal Portal System
- ADH Antidiuretic hormone
- Oxcytocin
Sexual Differentiation
(Involves specific substances)
Sex differentiation: process… group of unspecified cells develop into a functional recognizable group of cells (ex: male and female reproductive tracts)
Sex Determination: A system that determines the sexual characteristics.. GENES, ALLELES or Hormonal parameters. Ex: vulva, penis
Karyotype: This describes the chromosomal complement of an organism, X, Y
Dog: 78 XX (female), 78 XY (male)
Phenotype: observed characteristics that depend on the genotype and affected by the environment
Chimera: produced by the fusion of two different zygotes
Mosaic: an individual with two different cell lines that originated from the same individual
SExual differentiation 3 Stages
- Chromosomal Sex (Karyotype): determined at fertilization , XX or XY
- Gonadal Sex: Sry gene induces testes formation
- Phenotypic sex: determined by substances produced in the male testes to cause regresssion on the female tract
Sexually indifferent Stage
Microanatomy of Sexually indifferent Stage
Primordial germ cells: (primary undifferentiated stem cells that will differentiate toward gametes)
- Originate in the yolk sac
- Migrate trough the hindgut to the undifferentiated gonad within the dorsal body wall (a.k.a genital or gonadal ridge)
Pronephros Primitive Kidney
Mesonephros male (female regress)
Metanephros functional kidney
Mesonephric ducts (Wolffian ducts) male (female regress)
Paramesonephric ducts (Mullerian ducts) Female (male regress)
Primitive sex cord
Primitive germ cells
Sex Determination Male Key Players
Initially, Testis determining Factor (TDF) and Sex Determining Region-Y (SRY) causes production of TESTOSTERONE
- Antimullerian Homrnone secreted by Sertoli Cells (AMH) causes degeneration of the paramesonephric duct
- Dihydrotestosterone causes development of penis
Sex Determination female Key Players
XY chromosomes with Sex Determining Region-Y and Testis determining factor
- No SRY protein
- Ovaries develop
- No Anti-Mullerian Hormone
- Paramesonephric ducts become the oviducts, uterus, cervix, and part of the vagina
- Complete female tract
Developmental Sequence of the Testis
Level of Gonadal Ridge:
- Anti-Mullerian Hormone produced by Sertoli Cells
- Testosterone prescence causes regression of female duct system
- Paramesonephric duct (Mullerian duct) Regress (Antimullerian Hormone)
- Mesonephric ducts join Rete Tubules (future Rete Testis) becomes Efferent ducts, Epedidymis, and Ductus Deferens
- Mesonephric tubules become Seminiferous Tubules
- Undifferentiated sex cords become Seminiferous tubules
- Tunica albuguinea remains
Male Fetal Maturation: Testes Descent
Prior to descent, they are in the retroperitoneal position
The gubernaculum connects the fetal testis to the peritoneum
After the Gubernaculum goes through the inguinal ring, ther is a rapid growth of the distal gubernaculum
Once the testes are through the inguinal region they are pulled through because the gubernaculum shrinks. Abdominal visceral growth pushes them too.
The Scrotum has vaginal tunics where the testes are kept.
Endocrine Reproduction
Simple and Neurocrine Reflexes
Both start with Stimulus, Sensory Neuron, Transmission, and go different ways via Efferent neurons.
Simple Neural Reflex: Employs nerves that release simple neurotransmitters directly onto target tissue.
Ex: muscles for sexual behavior are stimulated by thermal, tactus, or visual factors. Efferent neurons release neurotransmitters to sweat glads, scrotm, etc.
Neuroendocrine Reflex: Requires a neurohormone (released by neuron) to enter into blood and act on remote target tissue
-signal goes to brain, release neurohormone into bloodstream, target tissue
Ex: The hypothalamus is the neural control center for Repro Hormones. Calf suckling stimulates release of oxytocin and mammary gland is the target tissue
Mechanism of defeminization of Hypothalamus
Female ESTRADIOL
Testosterone produced by the testes penetrates the BBB.
- Once testosterone is in the brain, it is converted to ESTRADIOL
- ESTRADIOL defiminizes the hypothamlamus because the surge center does not develop
***Steroid hormones go back and forth in form***
Estradiol bound by Alpha-Fetoprotein which prevents estradiol from crossing the BBB
Aromatase Enzyme converts testosterone to Estradiol Alpha-Feto-Protein (¤E2)
Average age of puberty
Determine more by weight than by age
Estrous Cycles Categorization
Different type of breeders
• Estrous cycles are categorized according to the frequency of occurrence throughout the year. There are 3 types:
cattle I21 ) Swine Rodents dogs , ,
- Polyestrus -
• Have a uniform distribution of estrous cycles throughout the entire year • Cattle, Swine, Rodents
2.
Seasonally Polyestrus
• Have “clusters” of estrous cycles that occur only during a certain season of the year
Elk
• Short-Day Breeders – they cycle as the day length is decreasing (fall) sheep goat, deer , ,
- Sheep, Goats, Deer, Elk
- Long-Day Breeders – they cycle as the day length increases (spring)
• Mares
- Monoestrus
• Have only one cycle per year
• Dogs, Wolves, Foxes, Bears
• Domestic dogs typically have 3 estrous cycles per 2 years, but are classified monoestrus
Estrous Cycle
2 Major Phases
- Follicular Phase
- Primary Ovarian Structure: Large Follicle (s)
- Hormone: Estradiol (secreted by follicles)
- Period: from Corpus Luteum regression to ovulation - Leutal Phase
- Corpus Luteum
- Progesterone (secreted by CLs) blocks Estradiol
- Period: from ovulation to CL regression
- Follicles continue to grow/regress, but do not produce high quantities of Estradiol
Estrous Cycle 4 Stages
Follicular phase
Proestrous
Estrus
1. Proestrous:
Begins when progesterone declines as a result of Luteolysis
Ends at the onset of Estrus
2-5 day period depending on the species
Transition from Progesterone to Estradiol
FSH & LH
Antral Follicles mature for ovulation and tract prepares for estrus and mating
2. Estrus:
Peak Estradiol secretion by dominant follicles
Duration varies between species
3. Metestrous
Corpus Luteum formation (Luteinization)
Begining of Progesterone secretion
Transition from Estradiol to Progesterone Dominance
4. Diestrus
Sustained secretion of high levels of Progesterone from mature Corpus Luteums
Longest stage of the cycle (2/3 of the time)
Ends with Luteolysis
Behavioral Estrus Signs in different species
Estrous Cycle Phases (Follicular & Luteal)
Estrous Cycle Stages (PEMD)
Exceptions
BITCH & QUEEN
Anestrus: 5 months
Follicular Phase
- Proestrous: 9 days; drop of blood FSH (Inhibin secreted by developing follicles inhibits FSH secretion)
- Estrus: 9 Days; decreasing Estradiol (secreted by Granulosa Cells of Follicle) and rising Progesterone
Ovulation 2-3 days after LH Surge (primary oocyte needs 2 days to mature)
Fertilization 48-72 hours after ovulation. The delay allows Superfecundation (multiple ovulations produce multiple oocytes during a single estrus period that are fetilized by spermatozoa from different males) in canids.
Luteal Phase
Diestrus: 2 months
Both pregnant and open bitches are considered to be in Diestrus. Pregnancy status does not alter the length of diestrus. Bitches that do not become pregnant are pseudopregnant
Reproductive Cyclicity of Queens with or without Copulation
Proestrous
Estrous
Proestrous: Interestrus period in queen not mated (ovulates only if stimulated)
Period of about 7-10 days
Growing follicle, but it dies if not stimulated
Diestrous about the same length as gestation
Anestrus:“Without cyclicity”
Females that do not exhibit regular estrous cycles
Causes of anestrus:
-Pregnancy (NOT IN CATS) Quees come back in heat within days after parturition
Cattle wait 40-45 days to get pregnant again
- Presence of offspring
- Season (photoperiod)
- Stress
- Pathology
Lactation Anestrus
Cyclicity is completely supressed in SOWS during lactation
In suckled cows, it is delayed as much as 60 days (Supression of LH)
-Duration influence by suckling sessions. 3 or more sucklings per day causes partum anestrus
-Dairy cows typically do not display lactational anestrus because the calf is removed
-Beef cows about 60 days
Possible role of Kisspeptin Neurons in regulation of cyclicity in long and short day breeders
- Increased day length = excitation of retinal neurons
- Retinal neurons synapse in suprachiasmatic nucleus
- Inhibitory neurons convert excitatory reponse to an inhibitory response
- Postsynaptic adrenergic fiber- decreases norepinephrine secretion
- Decreased norepinephrine = reduced melatonin secretion from pineal gland (pinealocyte)
- Low melatonin results in excitation to the RFRP neurons and they increase secretion of neurotransmitter RFRP-3
- Increased RFRP-3
- Short-day breeders: Decreased Kiss-10 causes decreased GnRH = Decreased FSH, LH
- Long-day breeders: Increased Kiss-10 causes increased GnRH = Increased FSH, LH
Folliculogenesis
Primary Ovarian Structures
Primary Follicles: from primordial follicles, begining of development
Secondary Follicles: Zona pellucida present
Antral (Tertiary) follicle (s):
- Developing antral follicle, Cortex present
- Antral (dominant) follicle: Antrum present (filled with follicular fluid) Big
Ovulating Follicle: Erupts and Oocyte exits
Corpus Luteum: right after ovulation
Corpora Albicans
*In general all types of follicles are present within the ovary at any point in time*
*Developing and functional Corpora lutea may or may not be present depending on the stage of the Estrous cycle* Exception Mare
Follicular Phase
Governed by?
Four significant events?
What are they key players in Follicular Phase?
What role does Inhibin play?
What role does Estradiol have?
Which hormone exerts positive feedback on Hypothalamus to cause LH Surge?
Which hormone produces negative FSH feedback on Hypothalamus?
Where and what cells secret Inhibin and Estradiol?
Governed by Ovary, Hypothalamus and Anterior Pituitary through secretion of ESTRADIOL in the absence of Progesterone
Events:
- FSH (primarily) & LH released from anterior lobe of Pituitary
- Follicular preparation (growth) for ovulation
- Sexual receptivity
- Ovulation (LH highest peak)
Dominant Hormone is ESTROGEN during follicular phase
- Changes in reproductive tract
- Behavioral changes
- Controls onset of preovulatory LH Surge
Key Players in Follicular Phase
-Tonic Center of the Hypothalamus: releases Gonadotropin Releasing Hormone, which stimulates FSH> and LH release from anterior lobe of pituitary gland
FSH> and LH cause the growth and development of follicles on the ovaries
The follicles produce ESTROGEN
-Surge Center of the Hypothalamus: responds to Positive Feedback to increase levels of ESTROGEN in the absence of Progesterone
*Positive feedback causes hypothalamus to release large quantities of GnRH*
-GnRH causes LH Surge, which results in OVULATION
**The Surge Center is turn ON once ESTROGEN reaches a threshold level**
Inhibin is secreted from Granulosa cells of Antral Follicle (largest) and inhibits FSH secretion by targeting Gonadotrophs of anterior lobe of pituitary gland
Estradiol (also secreted from Granulosa Cells) levels reache threshold and it stiulates secretion in Large Quantities of GnRH, which leads to LH SURGE preovulation
What are the two groups of GnRH neurons in the hypothalamus?
What are the results of stimulation to those neurons?
- The Surge Center
- Preovulatory increased GnRH = LH surge (Estradiol positive feedback = Lots of GnRH, thus FSH and LH secreted) - The Tonic Center
- Inhibin secretion from granulosa cells leads to decrease FSH release.
Summary of Preovulatory Hormones
- Decrease Progesterone due to Luteolysis
- Release of negative feedback of Progesterone at level of hypothalamus increases GnRH
- Increase GnRH increases FSH and LH
- Increasing Estrogen production by developing follicle
- Positive feedback of Estrogen on GnRH SURGE CENTER hypothalamus
- LH Surge triggered
Antral (Tertiary) Follicle (s) Pictures
Granulosa Cells
OOcyte
Hilus
Theca cells
Follicular Dynamics
Follicular Growth and Degradation
- Recruitment: phase in which a small cohort of Antral Follicles begin to grow (emerge) and secrete ESTROGEN
- Selection: Follicles are selected from previously recruited follicles
- Either die (atretic) or progress further - Dominance: one or more large preovulatory follicles that will undergo ovulation
- Monotocous spp or Polycocous - Atresia: Antral Follicles in which the antrum dissapears (they die)
**Most follicles are recruited during atresia.. very few advance to ovulation**
Atresia occurs continously during folliculogenesis
Follicular Dynamics Hormones during
Recruitment
Selection
Dominance
Recruitment:
- High FSH
- Low LH
No inhibin, No Estrogen
Selection:
- Low FSH
- Moderate LH
- Low Inhibin
- Low to Moderate Estrogen
Dominance:
- Low FSH
- High Inhibin
- High LH
- High Strogen
How does the Follicle Produce Estrogen on a cellular level?
2-Cell, 2-Gonadotropin Model
- When LH binds to Theca Interna Cells it causes synthesis of enzymes that convert Cholesterol to Testosterone. cAMP protein Kinase system
- The Testosterone travels from Theca Interna Cells to Granulosa Cells. When FSH binds to the Granulosa Cells it causes synthesis of enzymes that convert Testosterone to Estrogen. cAMP protein Kinase system
- The Estrogen leaches into the capillaries and become systematic
- The systematic Estrogen has effects on the brain, mating posture, phonation, and physical activity.
OOGENESIS
Begins with the development of primordial germ cells in the embryo
Primordial cells divide mitiotically into OOGONIA
OOGONIA divide into PRIMARY OOCYTES to enter into the first Meiotic prophase
At the end of meiotic phase the nuclear material is arrested. This arrest is call Dictyate, a form of Nuclear Hibernation
PUBERTY
At puberty, the female begins to cycle and ovulate.
The LH surge allows the meiotic arrest to be lifted and the first meiotic division takes place
LH SURGE = Meiotic Inhibition Lifted
Secondary Oocyte
The meiotic division results in the formation of secondary oocyte which possesses the first polar body (1/2 of genetic material). Primary oocyte 4N to 2N first polar body
First Polar Body 2N
Second Polar Body 1N (ovulation)
The bitch ovulates a primary oocyte, eggs not fertile until two days later
Ovulation, Luteinization, and Luteolysis
Ovulation
- LH Surge dependent
- Most species 24 hrs except Mares (3-5 d)
- The bitch ovulates 2-3 d after LH surge
- Cow Ovulates after Estrus
Ovulated follicle: Collapses, fills with blood, becomes a Corpus Hemorrhagicum (CH)
Secondary Oocyte is ovulated except canids (primary oocyte)
Preovulatory LH Surge
It is critically important bc sets in motion a series of biochemical reactions that lead to ovulation. Ovulation is a complicated process that includes the purposeful destruction of follicular tissue.
*Ovulation is brought on by elevated blood flow, break down of connective tissue, and ovarian contractions*
Induced Ovulators
They don’t respond to GnRH and LH Surge
-Require stimulation of the vagina, cervix, and/or uterus for ovulation to occur
Ex: Cats, rabbits, ferrets, Giant Fruit Bat, 13-Lined Ground Squirrel, Sumatran Rhinos.
-Camelids in addition to stimulation require a substance in seminal plasma for ovulation (Ovulation Inducing Factor-OIF or Beta-Nerve Growth Factor-B-NGF)
Copulation and ovulation
- Copulation stimulates sensory nerves in the vagina and cervix
- Impulses are then relayed to the spinal cord
- Impulses are then relayed to the Surge Center in the Hypothalamus
- If sufficient stimuli is provided, neurons in the perovulatory center fire, causing a large quantity of GnRH to be secreted, which stimulates an LH Surge
Luteal Phase: Metestrus and Diestrus
Three main events
- Luteinization of follicular cells to luteal cell
- Granulosa Cells to Large Luteal cells and Theca Cells to Small Luteal Cells - Growth and development of the Corpus Luteum and production of Progesterone
- Luteolysis
Luteal Phase
- Begins right after ovulation
- CL formation first
- Progesterone increases
- Diestrus: CL is fully functional and Progesterone Plateaus
- During the last 3 days of the Luteal Phase the CL Lysis and the Proestrus Phase is initiated
- Follicular Phase is resumed
Formation of the Corpus Luteum
What membrane begins to breakdown?
Corpus Hemorrhagicum
Functional Corpus Luteum
CL originates from an ovulatory follicle
The basement membrane begins to breakdown as ovulation nears
The Corpus Hemorrhagicum forms when small blood vessels rapture and Theca and Granulosa Cells mix
Formation of the Corpus Luteum
What membrane begins to breakdown?
Corpus Hemorrhagicum
Functional Corpus Luteum
Luteinization
When the Corpus Luteum is a mixture of Large Luteal Cells (originate from Granulosa Cells) and Small Luteal Cells (originate from Theca Cells)
-Remnant of Follicular Antrum present sometimes
Luteinization
-Theca & Granulosa Cells (produced Estrogen prior to Ovulation) transformed into Luteal Cells
-Progesterone Produced by Luteal Cells
Corpus Luteum
-Oxytocin and Relaxing hormones produced by CL
Corpus Lutem in Mares and Sows
Mares can’t palpate a CL because of ovulation fossa. Ovary is inside out.
The Physiologic Effects of Progesterone (produced by the CL)
Hypothalamus
Anterior Pituitary
Uterus
Mammary Glands
Hypothalamus:
-Negative feedback:
Reduces basal GnRH amplitude and frequency
Supression of FSH & LH
Prevents behavioral estrus
Stops preovulatory LH Surge
Anterior Pituitary
-Negative Feedback:
Uterus
-Positive influence on uterine glands to secrete “Uterine Milk” (histotroph) for potential concepts
Reduces myometrial tone (Except in mare)
Mammary Glands
Prior to parturition causes final alveolar development
Reproductive Physiology of the Male and Fertilization
Tonic Center
No Surge Center
Endocrinology of the Male
Males don’t have Surge Center in Hypothalamus
Tonic Center
-Basal release of GnRH in frequent, intermitent bursts througout the day and night
Trigger release of LH and FSH
Testis
Leydig LH (interstitial cells): analogous to the Theca interna cells in females
- Contain receptors for LH
- Produce Testosterone
- Secrete Inhibit
Sertoli (Nurse) cells: analogous of Granulosa Cells in females
- Contain receptors for FSH
- Convert Testosterone to Estradiol
- Secrete Inhibin
***FSH longer half-life than LH***
Where does formation of the spermatozoa starts?
What do they divide into?
Formation of Spermatozoa starts near the basal membrane of seminiferous epithelium
The spermatogonium divide to form other spermatogonia and ultimately primary spermatocytes
The early sperm cells all develop in the space between two or more Sertoli Cells (bind FSH and secrete testosterone) and are in contact with them. The intracellular bridges between adjecent germ cells in the same cohort or generation
- Spermatids
- Secondary spermatocytes
- Primary spermatocytes
- Spermatogonia
**Sertoli cells convert Testosterone to Dihydrotestosterone and Estradiol**
Dihydrotestosterone, Estradiol, and Testosterone is transported in the blood and exerts NEGATIVE FEEDBACK on Hypothalamus GnRH neurons, supressing FSH.
Both Sertoli cells and Leydig secrete Inhibit (inhibits FSH secretion)
Where are Spermatozoa produced?
What is Spermatogenesis and the goals?
What are the phases of Spermatogenesis?
Process of producing spermatozoa in the seminiferous tubules
Provides continual supply of male gametes (billions of sperm each day)
Provides immunologically priviledge site (Blood Testes Barrier) Developmental cells are not destroyed by male’s immune system
Three Phases
- Proliferation: primary spermatocytes, mitotic division (BASAL)
- Meiotic Phase: involves primary and secondary spermatocytes (ADLUMINAL)
Genetic diversity DNA replication
- Differentiation Phase: No further cell division (ADLUMINAL)
Transformation from spermatid to spermatozoa
From spherical shape to having a head, midpiece, and flagellum
Lumen of Seminiferous Tubule
Sertoli Cells
Basal Lamina
Tight Junctions
Leydig Cells
What are the stages of the Differentiation Phase in Spermatogenesis?
- Golgi Phase
- Acrosomic vesicle formation
- Spherical spermatid has a well developed golgi apparatus
- Sitting on top of the nucleus
- Pro-acrosomatic granules - Cap Phase
- Acrosomic vesicle spreading over the nucleus - Acrosomal Phase
- Nuclear and cytoplasmatic elongation - Maturation Phase
- Final assembly that forms a spermatozoan
Differentiation-Maturation Phase
What parts of the spermatozoa develop/change during this phase?
How does Spermatozoa Move?
Mitochondria form a spiral assembly around the flagellum that defines the midpiece.
- Head
- Neck
- Middle piece: gives tail flexibility when it becomes mobile
- Principle piece: Makes up a majority of the tail
- Terminal piece: end piece where only the microtubules end
Capitulum: Fits into the depression in posterior nucleus
Movement
Flaglellum: beats in a snake-like fashion to propel forward
Geometric Clutch Model
9 pairs of microtubules arranged radially around two central filaments
What is Spermiation?
What is the cycle of the Seminiferous Epethelium?
What are Spermatogenic waves?
13 Cycles, 8 Stages
Spermiation is the process of continual release of spermatozoa into the lumen of the siminiferous tubules
Spermatozoa in different stages of development
Cycle of the Seminiferous tubules
The time it takes for progression through all stages
The time frame differs between species
Bull and Dog: 61 days
Ram: 47 days
Boar: 39 days
Stallion: 55 days
Spermatogenic Waves
- Spiral movement, like a corkscrew towards the inner part of the lumen
- They are able to do this because they have gap junctions which allow communication between developing cells
At any given cross sectional location along the seminiferous tubule, once can observe the different stages of the cycle (Stage I, I, III, IV, V, VI,VII, VIII)
Sperm and Seminal Plasma
Capacitation and Spermatozoa
What has to happen before Spermatozoa reaches maximun fertility?
What is the sequence of events leading to Fertilization?
What are the barriers to fertilization (oocyte related)?
Mixing sperm and seminal plasma coats the sperm with proteins that must be removed for maximal fertility
Capacitation: stripping these plasma membrane proteins by Uterine factors
The removal of these surface molecules exposes portions of the molecules that can bind to the Zona Pellucida of the Oocyte.
**Spermatozoa must reside in the uterine tract before they acquire maximum fertility**
Fertilization Sequence of Events
- Hyperactive motility (disco dancing, in one spot)
- Binding to Zona Pellucida
- Acrosomal Reaction
- Penetration of Zona Pellucida
- Sperm-oocyte membrane fusion
- Sperm engulfed
- Decondensation of sperm nucleus
- Formation of male pronucleus
Barriers to fertilization
Cumulus Cells
Zona Pellucida
Oocyte membrane (oolema)
Acrosome Reaction
What happens if the sperm enters prematurely?
What happens during Cortical reaction?
If Acrosome reaction occurs prematurely, sperm can’t penetrate the Zona Pellucida
If the Acrosome reaction fails to occurs, sperm can’t penetrate ZP
Before the reaction occurs all the membranes of the head are intact.
During acrosome reaction
The plasma membrane overlaping the acrosomal membrane begins to fuse with the outer acrosomal membrane. The fusion creates pores that allow acrosomal enzymes to pass, which leads to ZP penetration
- Spermatozoa enters perivitelline space
- The membrane fuse and the cortical reaction is induced
- The equatorial segments and the post nuclear cap are intact
During the Cortical Reaction
-The sperm head attaches to the oocyte plasma membrane (vitelline membrane)
Results: Condensation of sperm nucleus
- ZP binding
- Vitelline membrane changes
- Prevents other sperm from binding to ZP
*The plasma membrane of the oocyte fuses with the equatorial segment and engulfs the spermatozoa*
- Cortical contents are released by exocytosis
- Decondensation: Sperm nuclear membrane disappears and the nucleus of the sperm decondenses
Syngamy is the fusion of female and male pronuclei
Zygote from Greek”Yoked” the one-cell organism that forms after syngamy has taken place
Embryo “That which grows”: embryo is multicellular
What is an ootid, polar bodies, zygote?
Ootid if the female and male pronuclei along with the 1st and 2nd polar bodies
Zygote unicellular organism resulting from the fusion of pronuclei
- It undergoes cleavages (miotic dividisions)
- Gives rise to daughter celss called Blastomeres
What is a Morula?
What happens after the Morula continues to divide?
What three forces govern hatching of blastocysts?
A four-celled embryo continues to divide and eventually become 8-celled, which is then called Morula
After the Morula continues to divide Early Blastocyst develop
- Inner cell mass
- Blastocoele: cavity
- Trophoblast: single layer of cells
Blastocyst hatches from Zona Pellucida and becomes free-floating
Forces involved in hatching: Growth & Fluid accumulation, Production of Enzymes by Trophoblastic cells, Contraction of the blastocyst.
Blastomere is Totipotent: up to the 8-16 cell stage
Post hatching Blastocyst Growth Examples
Cow
- Day 13 = 3mm
- Day 17 = 250 mm
Pig
- Day 10 = 2 mm
- Day 12 = 200 mm
Rumminant
-Filamentous, thread-like structure
Mare Blastocyst
-Remains spherical
Extraembryonic Membrane Development
Attachment times
Accounts for the rapid expansion of the blastocysts
Extraembryonic membranes:
-Yolk sac develops from primitive endoderm
-Chorion develops from the Trophoblast along with primitive endoderm & mesoderm
-Ammnion from primitive endoderm, Trophoblast, and mesoderm
-Allantois fuses with the Chorion. The chorion eventually attaches to uterus, while amnion will provide fluid-filled protective sac.
They are essential to fascilitate attachment to uterus
Cows: Day 18-22
Mare: Day 36-45
Sow and Ewe: Day 15-18
Placentation
How does the placenta develop?
The Yolk sac feeds the early embryo
Day 30 still not implanted yet
Day 36 embryo goes to the top and umbillicus connects
Placenta originates from Chorioallantois
- Develops from the Chorionic Girdle cells
- Allanto-chorion
Cotyledonary Placenta
- Caruncle: mom drives the car
- Cotyledon: baby rides in the Cot
Degree of invasiveness - Number of tissue layers between fetal and maternal blood
Placenta assists in parturition produces Relaxin
It secretes Lactogen in ewes
It takes over from ovarian source of Progesterone
- 6-8 mts in cows
- 50 days in ewe
- 70 days in mare, fully functional 100-120 days
- Epitheliochondrial
- least intimate, both maternal and fetal epithelium are intact
- Pig, horse, Cow, Ewe, Doe - Endoepitheliochorial
- Complete erosion of endometrial epithelium
- Dog, Cat - Hemochondrial
- Chorionic epithelium is indirect apposition to maternal pools of blood
- Primates, rodents
Where does sensory information originate and where does it go?
Stimulus (Pain, Temperature, Rude touch) to Dorsal Root Ganglion
Sensed by Primaty Sensory Neuron
Travels to Spinal Cord to
Anterolateral Paths to Secondary Neuron to
Thalamus: Ventral Lateral Nucleus to Primary Somatosensory Cortex in the brain
**Sensory processing can occur at the simple level in spinal cord. It stiulates a motor output and results in apropiate behavior**
OR
Sensory Processing goes to Cortical Processing (Considered Response), Subcortical Processing (Early Response) and Motor Output.
Cortical Processsing: Basal Ganglia Loops & Competition
Subcortical Processing: Basal Ganglia Loops & Competition
Spinal Cord and Spinal Nerves
What is a spinal Segment?
How is the Spinal Cord Organized?
Spinal Nerves have Somatic, Visceral, and Sensory Neurons
Spinal Segment is an imaginary boundary of the spinal cord midway between two adjecent spinal rootlets.
Example: Spinal nerve C8 is really between C8 and T1 vertebrae
Spinal Cord Organization
- Dorsal Fasciculus
- Dorsal Funiculus
- Dorsal Median Sulcus
- Dorsal Intermediate Sulcus
- Dorsolateral Sulcus
- Dorsal Root
- Dorsal Ganglion
- Main Trunk of Spinal Nerve
- Ventral Root
- Ventrolateral Sulcus
- Ventral Median Fissure
- Ventral Funiculus
- Lateral Funiculus
Dorsal Horn, Ventral Horn, Intermidiate Substance
-White Commissure
Ascending Tract
Projection Neuron
Interneuron
Spinal Motor Neuron
Sympathetic Trunk Ganglion
****Isolateral: Stays on the same side. Contralateral: Opposite side (Conscious)
What are Dermatomes?
What is a LMN?
Brachial Plexus Innervation
Sensory Dermatomes are cutaneos map
They are not completely independent, they overlap in some areas
Sensation from Peripheral Nerves ravel to an specific region of the spinal cord
Motor Output = Lower Motor Neuron
- Skeletal muscle
- Terminal branch of peripheral nerve
- Nuromuscular Synapse
- Ventral Root
- LMN in ventral horn
Brachial Plexus
Forelimb innvervation
C6-T1
Suprascapular, Axillary, Ulnar, Musculocutaneous, Radial, and Median Nerves
Lumbosacral Plexus
L4-S3
Femoral, Pelvic, Obturator, Saphenous, Sciatic, Peroneal, and Tibial nerves
Are all motor actions generated by higher centers?
What are the components of a simple arc reflex?
For both Somatic and Autonomic systems (in the cord or brain), sensory inputs can stimulate a motor neuron directly to complete a Local Reflex Arc, where no brain integration occurs
Spinal Reflex Arcs
Sensors:
-Muscle Spindle (Ia) triggers Alpha-motor (neuron) contraction
-Golgi Tendon Organ (Ib): of the patellar tendon senses muscle force on tendon, triggers Alpha-motor Inhibition
“Monosynaptic” Reflex. Myotatic Reflex a muscle stretched
Example: Quadriceps Reflex
-The quadriceps reflex testes the extensor reflex mediated by the Femoral Nerve
Action: Quick extension of the Stifle Joint induced by tapping the straight patellar ligament with a percussion hammer
Nerve Involved: Femoral Nerve
Cord Segments: L4-L6
Full Reflex Involves Intersegmental Coordination Femoral n. >L4-L6, Ipsilateral Flexor Inhibition
Polysynaptic Reflex
More complex interaction, more typical of a reflex organization
Interneurons
Ipsilateral Activation/Inhibition
Contralateral Activation/Inhibition
Example: Quadriceps femoris mm., Muscle Spindle (Ia), Golgi-tendon (Ib), Femoral n. & Sciatic Nerve and Inhibition of Flexors mm. Gracilus m. etc.
Spinal Reflex Arcs
Flexor Reflex and Extensor Reflex
Cutanerous Trunci Reflex
Full Polysynaptic Reflex
Example: Stimulus of pain in foot/toe
More complex and more interactions of the entire limb
- Sensors: touch and pain
- Responder Contraction:
Stimulation of Flexor mm. Ipsilateral
Inhibition of Extensor mm. Contralateral
-Responder Inhibition
Ipsilateral Extensor mm.
Contralateral Flexor mm.
Cutaneous Trunci Reflex
C8-T1
Fasciculus Proprius Spinal Cord Tract
Used to Evaluate other portions of the spinal cord
Sensor: touch or pain
Reponder Contraction:
-Cutaneous Trunci mm.
Sensory Fiber, Fasciculus Proprius, Lateral Thoracic nerve, Cutaneous Trunci m.
Ascending Tactile Somatosensory Tracts to the Brain
Primary (or first order) neuron fibers synapse on Second Order Sensory Neurons in the CNS
- Relay the signal to higher brain centers
- Secondary Sensory Neurons can be considered Interneurons
- Some of these neurons send signals to local reflex arcs to eventually stimulate a motor neuron at the same level
Primary or First Order Sensory Neurons start at the Dorsal Root Ganglia
Ascending Tracts
- Tracts are situated more toward periphery of spinal cord in WHITE MATTER
- Each tract sub-serves a different sensory modality
**Pay attention to Nomenclature, which indicates their origen”
- Fasciculus Gracil
- Fasciculus Cuneatus & Spinocuneocerebellar Tract (C1-T5)
- Spinomedullary Tract & Dorsal Spinocerebellar Tract
- Spinocervicothalamic Tract
- Ventral Spinocerebellar Tract
- Spinothalamic Tract
- Spinoreticular Tract
- Fasciculus Proprius
Ascending Tactile Somatosensory Tracts to the Brain
Visceral Afferent Pathways
What happens to Sensory signals after entering the CNS?
nIML = Intermediolateral Nucleus >>Reflex Pathway
nSP = Sacral Parasympathetic Nucleus >>Reflex Pathway
Spinothalamic Tract
Example 1. Stomach
- Viscerosensory fiber of the Splanchnic Nerve to Dorsal Ganglion
- Intermediolateral Nucleus nIML
- Spinothalamic Tract
- Thalamus
Example 1. Colon, Rectus, Urinary Bladder, Repro Tract/Organs.
- Pelvic Plexus
- Sacral Parasympathetic Nucleus nSP
- Dorsal Root Ganglion
- Spinothalamic Tract
- Thalamus
Ascending Axons of 2nd order neurons synapse on 3rd order neurons in the Thalamus (GVA), Brainstem (GVA), or Cerebellum (General Propioception)
-If 3rd order neurons are in the Thalamus, these neurons send axonal projections to 4th order neurons in the Cerebral Cortex
Different Possibilites
- Spinal Cord >> Spinocervicothalamic Tract >> Spinothalamic Tract >> THALAMUS >> CEREBRAL CORTEX
- Spinal Cord >> Spino-olivary Tract, Spinopontine Tract, Spinomedullary Tract, Fasciculus Cuneatus >> BRAIN STEM >> THALAMUS >> CEREBRAL CORTEX
- Spinal Cord >> Ventral Spinocerebellar Tract, Dorsal Spinocerebellar Tract, Spinocuneocerebellar Tract >> CEREBELLUM >> THALAMUS >> CEREBRAL CORTEX
Higher Brain Centers
Sensory integration and output functions may be subconscious or consciuos
Primary Afferent and Secondary Afferent Neurons in the Somatosensory System
In the Somatosensory System all sensory neurons are the primary afferent sensory neuron themselves
-Distal axons endings are specialized to recieve and transduce sensory stimuli
PSEUDOUNIPOLAR Neurons
- Cell bodies in the Dorsal Root Ganglion
Head: Trigeminal Ganglion
Primary Afferent Neurons
- Receptor end: the end of the distal axon
- Sensory ending is specialized and transduce skin, muscle, and tendon stimuli
- May be encapsulated
The Sensory Transduction
The Receptor Potential
Sensory Encoding
Sensory Transduction
- Conversion of a stimulus into electrical energy that can be transmitted by sensory neurons
- In the somatosensory system, the stimulus may be pressure, stretch, temperature, or pain Noxious Stimuli
- Mediated by Ion Channels in the Sensory cells
Mechanoreceptors linked to Sodium Channels. They respond to Stretch-Sensitive Channels in sensory nerves
The receptor potential
Stimuli open ion channels in the cell membrane
- Electrical current generated will disrupt the cell’s RMP
- A net inward Positive current will depolarize and excite the cell (depolarizing receptor potential)
- If depolarization if sufficient magnitude, an action potential will be generated
- The more deformed skin the more depolarized
- Push hard enough and cause pain eventually
- No hyperpolarization
Sensory Encoding
-A higher stimulus intensity may cuase:
A higher amplitude receptor potential and so greater likelihook of action potential generation (firing threshold reached)
- Increased number of sensory receptors activated
- Increase in firing rate of the sensory neuron
- A change in the type os sensory receptor stimulated:
Nociceptor stimulation occurs at higher stimulus intensities than for mechanoreceptors or thermoreceptors
Rapidly Adapting Receptors during prolonged stimuli will decrease their firing rates. For example: vibrations when listening to music
-Phasic Receptors
Meissner and Pacinian Corpuscles
Slowli Adapting Receptors a.k.a Tonic Receptors respond to prolong stimuli, but continue to fire during the entire train of stimuli
-Tonic Receptors
Merkel Receptors Steady pressure on skin
Ruffini Receptor gradual skin stretch
Mechanoreceptors
Meissner’s corpuscles
-Touch, vibration, papillary dermis
Pacinian corpuscles
-Vibration, subcutaneous tissue
Ruffini’s corpuscles
-Stretch, dermis/joint capsule
Merkel’s
-Free nerve ending + Merkel’s disk, touch, pressure
Golgi-tendon Organ
-Propioception
Muscle Spindle Fiber
-Propioception
Somatosensory Pathways
Ascending tracts for conscious perception
-Dorsal Column - Medial Lemniscal System
Fasciculus cuneatus -thoracic region. *sensation, conscious proprioception from cervical-thorax/forelimbs*
-Primary afferent remains ipsilateral >> Nucleus Cuneatus >> Projection Neuron (2nd neuron)- decussates up medial lemniscus >> Thalamus >> Cerebrum
Fasciculus gracilis -cervical region. *Sensation trunk/pelvic limbs, No propioception*
-Primary afferent remains ipsilateral >> Nucleus Gracilus >> Projection Neuron- decussates up medial lemniscus >> Thalamus >> Cerebrum
Spinomedullary Tract -trunk/pelvic limbs. *conscious propioception*
Primary afferent neuron >> Nucleus thoracicus >> Projection neuron >> remains ipsilateral >> Nucleus-Z decussates >> Thalamus >> Cerebrum
Anterolateral System:
Spinothalamic Tract *pain, temperature, touch*
Primary afferent neuron >> Projection neuron-decussates at level of input >> Thalamus >> Cerebrum
Spinocervicothalamic Tract *Touch, pain* CONTRALATERAL
Primary afferent neuron >> Projection neuron- remains Ipsilateral >> Lateral Cervical Nucleus -3rd afferent decussates >> Thalamus >> Cerebrum
Cranium
Trigeminothalamic Tract *pain, temp, light touch, pressure, itch, proprioception, 2-point discrimination*
- Join with spinothalamic tract in Brainstem
- Afferent from trigeminal CN VII, IX, X, tongue
- Trigeminal Ganglia
General Propioceptive System
Concious Propioception Sense of limbs and body position
Subconscious Propioception Sense of gravity, weight shift
Muscle Spindle Sensor
- Detect changes in muscle stretch/length
- Spindles are made of special class of encapsulated mucle fibers called Intrafusal Muscle Fibers that have a separate sensory and motor innervation (Gamma, Alpha).
- They don’t create force
Muscle Spindle Afferent
-Type Ia
Group Ia Detect Rapid and dynamic changes in muscle movement
-Type II
Are slowly adapting and detect Static position of the limbs (constant muscles lengths)
-Golgi Tendon Organs are Type Ib. Activated when excessive tension on a muscle is induced (inhibitory)
Other Propioceptors
Pacinian corpuscles
Ruffini’s corpuscles
