Uvm Physiology - Group 2

Front 1

59.              Basal metabolic rate. Principle of calorimetry. Energy balance.

Back 1

"Basal metabolic rate: The number of calories (i.e. energy) required by the body to carry out all of its most basic functions to maintain homeostasis (i.e. respiration, balancing heat loss/production, etc.)

Factors influencing basal metabolic rate:
- BMR needs to be measured in a fasted animal
The most important factors influencing BMR include:
- Gender/sex of the animal (males > females)
- Age of the animal (young > old)
- Body condition (more muscled > more fat)
- Body size (surface area in relation to weight); Kleiber equation: BMR= K • bw0.75
- Neural and hormonal (somatic NS ? skeletal muscle; sympathetic ANS ? metabolic process)
- Endocrine: increases MR such as epinephrine, growth hormone, prolacting, T4-TSH
- Specific dynamic action or heat increment of feeding (measure after hepatectomy)
- E.g. increased nutrient imbalance = higher proportion of metabolisable energy loss
- Temperature (ectotherms vs endotherms):
- Increased body temperature corresponds to an increased MR
- Species
- Injury recovery
- e.g. 33% more energy required to heal broken bones)
- Stage of reproduction (gametogenesis, lactation, gestation)
- Misc. including shedding, moulting

Direct calorimetry:
- Uses an animal calorimeter: airtight, insulated chamber
- Animals do not store heat, therefore measurements taken over 24hrs are assumed to be equivalent to energy produced and lost
- The calorimeter heat loss by recording the air drawn through the chamber and the moisture content within

Indirect calorimetry
- Measurement of O2 consumption and CO2 production over time
- I.e. Measures respiratory exchange
? Determine respiratory quotient
? Uses a Douglas bag
? Normal respiratory quotient is 0.7 – 1.0
? Fattening animals have a quotient >1.0

Assuming all things are equal, male animals have a higher BMR than female animals for several reasons:
- Proportion of different body tissues: Male animals have a higher % muscle while female animals have a higher % of body fat; muscle requires more energy for maintenance and will therefore increase BMR of their female counterparts
- Differences in neural and endocrine function
"

Front 2

60.              Types and sources of energy. Energy values of different nutrients conversion.

Back 2

"Energy values of different nutrients:
- The energy value of each nutrient is measured by burning in a calorimeter
- Carbohydrates: 4.1kcal/g
- Protein: 5.6kcal/g (the real value of protein is 4.4kcal/g due to low oxygenating form of nitrogen)
- Fats: 9.45kcal/g


"

Front 3

61.              Intermediary metabolism of sacharides and lipids. Hormonal regulation of glucose maintaince in the blood plasma.

Back 3

"Glucose metabolism
- When glucose is absorbed, it can be utilised by the body in 3 main ways:
1) Glycolysis:
- Under aerobic conditions, glucose is converted:
pyruvate ? Krebs cycle ?oxygenation ?ATP production and CO2
- Under anaerobic conditions, glucose is converted:
lactic acid by mitochondria ? blood circulation ?liver ?Cori cycle
- This is the base for gluconeogenesis
2) Oxygenated glucose:
- It is the base to formation of acetyl CoA, which is precursor to fatty acids and cholesterol
- Can also be considered as utilisation of glucose for lipid storage
3) Storage as glycogen
- Glycogen is the stored form of glucose in the liver and muscles
- Glucose metabolism is the organic base formation of non-essential amino acids
- Monogastric animals: glycogen is hydrolysed in the liver and excess is stored as glycogen
- Ruminant animals: Microorganism activity in the rumen converts dietary carbohydrates to volatile fatty acids (VFA)

Lipid metabolism
- Intermediary metabolism of lipids involves lipid synthesis
- There are 2 main pathways:
1) Cytoplasmic
- Acetyl CoA acts as the precursor to the formation of palmitic acid
- This process takes place in the liver, kidney, adipose tissue, brain, lungs, and mammary gland
2) In adipose tissue:
- As storage of triglycerides
- VFAs are combined with glycerol in tissue
- Biosynthesis occurs by: glucose ? Acetyl CoA ? FA-CoA ? triglyceride
- Monogastric animals: glucose is the precursor
- Ruminant animals: Acetic acid is the precursor
- The liver is an important site of fat metabolism
- Poultry it is the only site of fat metabolism
- Ruminants liver and adipose tissue
- Pig: almost always in adipose tissue

Glucose regulation:
- Controlled by 2 hormones: insulin and glucagon
- Insulin:
- Promotes the storage of glucose and uptake of amino acids; increases protein and lipid synthesis; inhibits lipolysis and gluconeogenesis
- Secreted by beta cells in the pancreas (Islets of Langerhans)
- The primary stimulus is glucose (high blood glucose); other stimuli include amino acids (leucine), GIT hormones (pancreozymin and gastrin)
- Activates glucokinase for glucose metabolism and increases cell membrane permeability to glucose
- Glucagon:
- Secreted by the alpha cells of the Islets of Langerhans
- Secreted in response to hypoglycaemia or to stimulation by growth hormone
- It acts by increasing blood glucose levels by stimulating glycogenolysis in the liver
- An important treatment in hypoglycaemic coma (especially due to hyperinsulinism)
"

Front 4

"62.              Nervous system, general roles. Types and parts of neurons, functions. Convergence and divergence in neural networks."

Back 4

"General role:
- Input information from sensory receptors into the nervous system results in output instructions to muscles and glands
- Input information for the CNS originates in the external environment and internal body

Sensation (input) ? Decision (computation) ? Behaviour (output)
Perception (consciousness) and Evaluation (memory) influence the decision

Interaction with the hormonal system:
- Nervous system exerts control over almost all functions including the endocrine system
- The hypothalamus secretes hormones that regulate the pituitary and also act on the nervous system (feedback control system?)
- Glucocorticoids affects neuronal processes
- In general, the nervous system can act to illicit a quick response while the endocrine system acts to illicit a slow response

General outline of the nervous system:
Central nervous system (CNS): Includes brain and spinal cord
Peripheral nervous system (PNS): Includes muscular skeletal nerves
Autonomic nervous system (ANS): Includes the sympathetic and parasympathetic nervous systems

Parts of a neuron:
1) Cell body with a nucleus and usually organelles
2) Axon: single long process. Relay information from the nucleus
3) Dendrite: Smaller processes, often more numerous. Relay information to the nucleus (i.e. receive input from other neurons)

Types of neurons:
Unipolar cells: have a single process. Rare in higher vertebrates
Bipolar cells: Have 2 processes: an axon and 1 dendrite. Exemplified in the retina
Multipolar cells: Have 1 axon but many dendrites (e.g. motor neurons)

Convergence: Coming together of nerves i.e. convergence of peripheral nerves (input nerves) towards the CNS
Divergence: Breaking away of nerves from a common point i.e. the divergence of peripheral nerves from the CNS towards the poles of the body
"

Front 5

63.              Functions of nerve fibers. Types of propagation of nerve action potential.

Back 5

"Function of:
Nerve fibres: A process of the neuron, especially in the long slender axon which conducts nerve impulses away from the cell. Their function is to transfer the signal from the CNS to the tissues and vice versa. Allow for the connection between 2 neurons or the neuron and the target organ.
Somatic nerve: The sensory and motor nerves supplying the skeletal muscle and somatic tissue
These nerves should be:
- Myelinated fibres (diameter 2 – 20?m): These nerves need to transfer signals over long distances but the signals must be fast without loss over distance
- Unmyelinated fibres (diameter 0.5 – 2.0 ?m): These nerves would have a sensory function
- Somatic afferent nerves: Sensory neurons whose cell bodies reside in spinal and cranial nerve ganglia
- Somatic efferent nerves: Motor neurons originating in ventral gray columns of the spinal cord and certain ventral parts of the brain and are connected to striated muscles derived from embryonic somites

Dendrites: Receive input from other neurons therefore they relay information to the nucleus.
Axon: Carries the impulse output away from the cell body

Types of propogation:

Unmyelinated: The action potential spreads along the neuronal membrane such that there are areas of recovery ? active ? resting degrees of propagation. The speed of the signal is governed by the diameter of the axon (larger axon = faster impulse). Such an action potential cannot be maintained over long distances as the signal “fades” the farther it has gone

Myelinated: Myelin, a covering around axons, causes an increase in conduction velocity by allowing an action potential to propagate down a myelinated axon but the Na/K fluxes can only occur at the nodes (Nodes of Ranvier). It is at these nodes where the action potential signal is “boosted” (sort of like a power transistor). Saltatory conduction is the leaping action transfer of electric potential from node to node instead of a steady flow along the length of the nerve.

At the chemical junction: Calcium channels open allowing for ion influx, which causes neurotransmitter release across the synapse. The neurotransmitters bind to receptors located on the dendrites of adjoining nerves. Depending on the type of receptor and neurotransmitter released, a cascade is triggered that can inhibit or excite the post-synaptic cell. It is a 1-way process as released neurotransmitter is either broken down or pumped back into the pre-synaptic cell where it is rebound in vesicles. Thus it does not have to opportunity to cause auto stimulation.


"

Front 6

"64.              Neurotransmitters - types, localisation in the nervous system. Synapses."

Back 6

"Neurotransmitters:
1) Acetylcholine (Ach): Acetic acid ester of choline; it is a neurotransmitter at cholinergic synapses in the central, sympathetic, and parasympathetic nervous systems.
2) Norepinephrine: Structurally similar to noradrenaline. Secreted by neurons in the brain stem, hypothalamus, and by postganglionic neurons of the sympathetic system. Vasoconstrictor properties.
3) Dopamine: Hydroxytyramine, produced by the decarboxylation of dopa. It is a neurotransmitter in the CNS; secreted by the substantia nigra neurons.
4) Glycine: Non-essential amino acid that functions as an inhibitory neurotransmitter in the CNS; secreted by the synapses of the spinal cord
5) Serotonin: A hormone and neurotransmitter (5-hydroxytryptamine) found in many tissues. It has many physiological properties including inhibition of gastric secretion, stimulation of smooth muscle, and vasoconstriction. Found in the CNS, pineal body, brainstem neurons, median raphe, dorsal horns of the spinal cord, and the hypothalamus.
6) Glutamate: Non-essential amino acid. Secreted as a neurotransmitter by presynaptic neurons in the sensory fibres and in the brain cortex.

Synapse: The area where signals are transmitted from axon, and its collaterals, of one neuron to the axon, dendrite, or soma of another neuron, or to another cell. The synaptic cleft separates the two neurons and acts as an insulator which allows for redevelopment of the signal.

Synaptic delay: The time delay from the moment the signal arrives at the presynaptic terminal until a new action potential starts in the post-synaptic neuron. Due to several processes:
1) Releasing of neurotransmitter by the action of calcium channels
2) Diffusion of neurotransmitter across the synapse to the post-synaptic neuron
3) Binding of neurotransmitter to the appropriate receptor on the post-synaptic neuron
4) Illicitation of a response in the post-synaptic neuron by the binding of neurotransmitter
5) Initiation of a new action potential (or suppression if the neurotransmitter was inhibitory in nature)


Synaptic transmitters:
- The mediators excite the ion channels in the post-synaptic neuron; The transfer excitation from one neuron to another via a chemical intermediate
- This category of molecules is divided into 2 main groups according to size:
- Small molecules which act quickly
- Class I: Acetylcholine (Ach)
- Class II: Amines
- Class III: Amino acids
- Large neuropeptides which act slowly
- A) Hypothalamus releasing hormones
- B) Pituitary peptides
- C) Peptides that act on the brain and gut
- D) Peptides from other tissues

Function of synapses:
- The function of synapses can be summarised into 3 categories:
- A) Blocking function between 2 neurons
- B) Impulse divergence: changing from one impulse to a series of impulses
- C) Impulse convergence: Integration of impulses with the impulses from other neurons

"

Front 7

"65.              Functions of sensory receptors. Types of receptors, examples."

Back 7

"Receptor: A molecule on the surface or within a cell (in the case of steroid receptors) that recognises and binds with specific molecules, producing some effect in the target cell. Modified receptors are found at the end of sensory nerves and they respond to a variety of stimuli to illicit a response (e.g. thermoreceptors, baroreceptors, stretch receptors)
- Receptors are composed of proteins
- Consists of an extracellular, transmembrane, and intracellular components
- The ligand (neutransmitter, etc.) binds to the extracellular component; binding causes a conformation change and results in a cellular response
- Main function: to respond to the binding of the correct ligand and illicit a cellular response
- Responses can be:
- Opening of ion channels
- Initiation of chemical cascades (e.g. cAMP cascade)
- Changes to metabolism
- Changes in mRNA function (in the case of steroid receptors such as estrogen which have an intracellular binding capacity)

Sensory receptors: An endorgan at the end of an afferent neuron which is capable of stimulation by a specific change (physical or chemical) in the internal or external environment of the subject
- Located throughout the body
- From all tissues, these receptors provide the input information to the CNS
- Stimulus selective
- Classified according to their stimulation:
- Mechanoreceptors: Affected by physical changes to tissue such as stretch
- Thermoreceptors: Affected by changes in tissue temperature
- Chemoreceptors: Affected by changes in body chemistry concentration and pH (e.g. CO2)
- Nociceptors: General term for any sensory receptor that is sensitive to pain (i.e. receptors with the ability to activate the pain centres of the brain); thermoreceptors can become nociceptors during extreme temperature changes (e.g. contact with boiling water; hot objects)
- Telereceptors: A nerve terminal that is sensitive to stimuli originating at a distance. Such receptors exist in the eye and ear (light and sound waves respectively).


"

Front 8

66.              Functions of central nervous system. Inhibitory or/and excitatory processing of information input to CNS.

Back 8

"
- From evolutionary development, the CNS can be divided into 3 domains
- This division is from a functional point of view
- The divisions are:
1) Spinal cord
- Cells contributing to the sensory system are located in the dorsal gray columns of the gray matter; they receive collaterals and direct terminations of dorsal root fibres and send their axons either to the ventral horn for reflex connection or to the white matter
- Functions include:
- Nucleus dorsomarginalis: Forms a column extending throughout the length of the spinal cord; they receive afferent signals from sensory systems and project their axons into lateral funiculus of white matter
- Substantia gelatinosa: Chief associative centre of the dorsal horn for sensory systems
- Nucleus proprius: Relay for pain and temperature sensory pathways
- Nucleus dorsalis: Concerned with the signals of stretch receptors of muscle and project their axons into the cerebellum via the spinocerebellar tract
- Main Function summary: Serves as a passageway for activity passing to and from the brain; contains complex reflex mechanism (includes myotatic or stretch reflex, flexion reflex, crossed exterior reflex, scratch reflex, extensor thrust reflex); reflex mechanisms are more common in the dog than man

2) Lower brain or brain stem
- Controls many of the “subconscious activities” of the body
- Structurally includes: medulla oblongata, pons, mesencephalon, hypothalamus, thalamus, cerebellum, and basal ganglia
- Function control includes:
- Medulla and pons: salivary gland regulation, deglutition, mastication, suckling, respiration, cough, oculocardiac, sneeze, blood pressure maintenance, postural reflexes
- Hypothalamus: neuroendocrine regulation
- Amygdala: Stimuli association
- Limbic system: memory and cognition processes
- Hypocampus: memory of verbally or verbally encoded items; relationships between language and concepts (humans)

3) Upper brain or cortical level
- Includes the cortex
- This part of the brain is the storehouse of memory and in charge of many motoric functions (like vision)
- Region of the brain associated with personality
- Always functions with the other domains; the lower brain can work without the cortex but it is inefficient work
- The cortex is in charge of the thinking process
- Phylogenically, the newest part of the brain

Information processing:
- The brain is being continually bombarded with sensory input
- It must sort this input and determine what to store as memory; what sort of action is required
- The result is the brain must inhibit the synaptic pathway of some information and cause excitation of the pathways designated for memory storage
- Examples:
- 1) Attention: The brain determines which acoustic information is processed completely for content while discerning between the input of “background noise”
- 2) Tactile stimuli: The tactile stimuli of clothing is suppressed at the brain level and not brought to the attention of the individual unless conscious attention is brought to it
- Just think: we would go crazy if every stimulus were processed in its entirety. Not to mention, we would be very confused!
"

Front 9

"67.              Inhibition – direct, indirect, presynaptic, and postsynaptic. Summation and facilitation of impulses in synapses."

Back 9

"Direct inhibition: Nervous impulse inhibition by blocking at the synapse

Indirect inhibition: Nervous impulse inhibition by secondary inhibitory neurons. For example, Spinal cord stimulation of a neuron at a target tissue can also stimulate collateral branches from the same axon to interneuron cells or ranshaw cells; excitation of ranshaw cells causes inhibition of the surrounding motor neurons

Pre-synaptic inhibition: Inhibition of signal propagation occurring in the pre-synaptic neuron; i.e. the blocking of neurotransmitter release at the synapse and prevention of signal propagation; likely occurs by a prevention of the opening of the calcium channels; usually occurs in sensory fibres.

Post-synaptic inhibition: Decreased rate of discharge of a post-synaptic nerve cell that has been subjected to inhibitory stimulation (such as binding by the neurotransmitter glycine or GABA mediation); this may occur by the opening of the K+/Cl- channels such that internal potassium is exchanged for chloride ion thereby increasing the threshold for firing

Summation: Physiological summation at the synapse is a characteristic of the mammalian nervous system. It map be spatial, with additional synaptic junctions participating, or temporal, when succeeding stimuli catch up with the as-yet undischarged neurotransmitter. Seen in the retina of the cat (and other nocturnal animals) where many millions of photoreceptors are connected to only one million axons, resulting in maximal sensitivity to light

Impulse facilitation in synapses: Occurs when the stimuli is almost, but not enough, to pass threshold
"

Front 10

"68.              Memory and learning, definitions, types. Parts of the brain that are involved in memory processing. Function of hippocampus. Conditioning. "

Back 10

"Memory and learning
- The phenomena of memory and learning is brought about by chemical, physical, and electrical changes in the synapse
- Occurs when the brain selects what information for storage
- The brain activates the synapses to store it as memory
- Immediate memory: for a few seconds to minutes; occurs by repeated signals in the temporary memory trace or by facilitation or inhibition of the pre-synaptic terminal resulting in electrical changes
- Short-term memory: Lasts for minutes to weeks; activated by chemical and physical changes in the pre-synaptic terminal or post-synaptic membrane
- Long-term memory: Lasts for years; facilitated by structural changes in the synapse such as the addition of more terminals or increasing the area of vesicular release
- Consolidation: This process takes minutes to hours and if interrupted, the memory will not be kept; during consolidation, the memory is repeated over and over again thereby leaving a memory trace

Learning in animals:
- Imprinting: occurs at birth; recognition of species (self)
- Instrument conditioning or type II conditioning: The subject performs a specific act that has been previously designated; e.g. pressing a bar to obtain a reward (food)
- Operant conditioning: Learning in which a particular response is elicited by a stimulus because that response produces desirable consequences (reward)
- Classic conditioning or type I conditioning: Learning in which a response is elicited by a neutral stimulus which previously had been repeatedly presented in conjunction with a stimulus that originally elicited the response (also called respondent or Pavlovian conditioning)
- Discriminative conditioning
- Habituation
According to Dr. Halagan:
- Animal learning must distinguish between learning and playing
- Leaning = a change in behaviour
- Playing = a gain in experience; refinement of skills
- Experience = learning; it does not equal playing!
- Learned information and memory = behavioural change in animals
- Plasticity in reaction/process
- Minimum 2 step process
- 2 neuronal divisions: (1) facilitative neurons and (2) inhibition neurons; learning is the establishment of new communication branches between these 2 neurons. You cannot learn with only 1 neuron!
Learning in human beings:
- In addition to the condition observed by animals, humans can also learn applied or discriminative conditioning

Discriminative conditioning or Learning: The animal is able to distinguish one stimulus from among several to obtain reward. The ability to alter behaviour on the basis of experience; memory is the ability to recall past events at the conscious and unconscious level
Habituation: simple form of learning in which a neutral stimulus is repeated many times. It evokes less and less electrical response as it is repeated. Eventually the subject becomes habituated to the stimulus and ignores it. Also known as non-associative learning

Brain structures involved in memory
General:
- Non-declerative or reflexive memory: Classical conditioning, skills, and habits that are largely and often totally unconscious. Involves the striatum, reflexive tasks, and cerebellum
- Declerative memory: Involves conscious recall of events that have occurred. In humans, it is divided into immediate recall, recent (or short-term) memory, and remote (or long-term) memory; Involves the hippocampus, portions of the meidal temporal cortex

Hippocampus
- Clearly implicated in memory consolidation (lesions inhibit the ability to convert short-term to long-term memory)
- Important because it has reciprocal connections with many cortical areas that participate in higher-order sensory processing
- Information from the neocortex comes from frontal, temporal, and parietal regions which are relayed by cortical areas adjacent to the entohinal cortex
- The Entohinal cortex also has reciprocal connections with the hippocampus


"

Front 11

69.              Functions of spinal cord. Spinal cord reflexes. Reciprocal innervation. Autonomic reflexes integrated at the level of the spinal cord.

Back 11

"Sensory function
- Collect information from the body to the brain
- Cells which contribute to sensory systems are located in the dorsal gray columns of the gray matter
- They receive collateral and direct terminations of dorsal root fibres
- They send their fibres to the ventral horn for reflex connection or the white matter and eventually the brain
- Includes:
- Nucleus dorsomarginalis
- Substantia gelatinosa
- Nucleus proprius
- Nucleus dorsalis
Motoric function
- Nuclei serving the motor system are limited to the ventral horn and the intermediolateral cell column
- Divided into somatic motor activity (divided into medial and lateral nuclear groups) and visceral motor activity (limited to the intermediolateral cell column)
- Medial motor column: Extends throughout the entire column length; innervates the muscles of the axial skeleton
- Lateral motor column: innervates the remainder of the somatic musculature; limited to spinal cord levels T1 ? L3; includes the pre-sympathetic ganglia of the sympathetic nervous system
- Influenced by sensory neurons and interneurons
Vegetative function
- Lateral motor column: innervates the remainder of the somatic musculature; limited to spinal cord levels T1 ? L3; includes the pre-sympathetic ganglia of the sympathetic nervous system
- Sacral ANS preganglionic neurons are located in an analogous region of the spinal cord (lateral portion of the gray matter)
Spinal cord reflexes in the dog
- Besides serving as a passageway for activity to and from the brain, the spinal cord contains a very complex reflex mechanism
- 10x more of the total CNS activity takes place in the spinal cord of the dog than man
- Consists of a minimal 5 components:
- Myotactic reflex: Also called stretch reflex; if a limb is forcibly flexed, muscle tone is increased in the extensor and decreased in the flexor
- Flexion reflex: If a noxious substance is applied to the distal portion of a limb, the limb is quickly withdrawn from the stimulus; the receptors for this reflex are those subserving the pain sensory system
- Crossed extensor reflex: When the flexion reflex is elicited in a limb by application of a noxious substance, the opposite limb is extended
- Scratch reflex: Cutaneous stimulation will illicit scratching
- Extensor thrust reflex: If pressure is applied to the palmar/plantar surface of a paw, the limb is extended into a rigid column due to simultaneous contraction of both extensors and flexors
Reciprocal innervation
- When a reflex is initiated in the spinal cord (certain muscle), the antagonist muscle is automatically inhibited
- This neuron circuit is known as reciprocal innervation
- It also connects both sides of the spinal cord
Autonomic reflexes at the level of the spinal cord
- Lower part of the CNS but the spinal cord is capable of performing independent actions without brain input
- Some of these actions can be seen in a decapitated animal
- Myotatic reflex, flexion reflex, crossed extensor reflex, scratch reflex, and extensor thrust reflex can all be seen in the spinal animal
- Autonomic reflexes include: local vasoconstriction, local sweating due to stimulation of sensory fibres
"

Front 12

70.              Embryonic development of the brain. General functions of the brain.

Back 12

"Embryonic stem cells evolve into more specialized adult neural stem cells. In turn, these adult cells can differentiate into neuron- or glial-restricted precursor cells, the former with the potential to transform into neurons and the latter into support cells called oligodendrocytes and astrocytes.
Brain nerve cells, or neurons, are initially produced in the center of the developing brain. To function normally, neurons must migrate to the brain's cortex, or outer layer, and other structures.
From embryology:
Neurulation - The process begins when the notochord induces the formation of the central nervous system (CNS) by signaling the ectoderm germ layer above it to form the thick and flat neural plate. The neural plate folds in upon itself to form the neural tube, which will later differentiate into the spinal cord and the brain, eventually forming the central nervous system.
The anterior segment of the neural tube forms the three main parts of the brain: the forebrain, midbrain, and the hindbrain. Formation of these structures begins with a swelling of the neural tube in a pattern specified by Hox genes. Ion pumps are used to increase the fluid pressure within the tube and create a bulge. A blockage between the brain and the spinal cord prevents the fluid accumulation from leaking out. These brain regions further divide into subregions. The hindbrain divides into different segments called rhombomeres. Neural crest cells form ganglia above each rhombomere. The neural tube becomes the germinal neuroepithelium and serves as a source of new neurons during brain development. The brain develops from the inside-out.
Functions:
The main parts of the brain are:
• the cerebrum (the forebrain) made up of the right and left cerebral hemispheres
• the cerebellum (the hindbrain)
• the brain stem.
Cerebrum ? This is the largest area of the brain and is concerned with all higher mental functions, such as thinking and memory. It is made up of two halves or hemispheres. The right cerebral hemisphere controls the left side of the body and the left cerebral hemisphere controls the right side of the body.
Each cerebral hemisphere is divided into four areas, known as lobes: the frontal, parietal, temporal and occipital lobes. Each lobe controls a different range of activities.
Cerebellum ? This is the back part of the brain and is concerned with balance and coordination. These activities are carried out automatically (subconsciously) by this area of the brain and are not under a person's control.
Brain stem ? This controls the basic functions essential to maintaining life, including blood pressure, breathing, heart beat and also eye movements and swallowing. It is the bottom part of the brain and connects the cerebral hemispheres to the spinal cord.

"

Front 13

"71.              Functions of basal ganglia, limbic system, and amygdala."

Back 13

"Basal ganglia
- Set of components in the deep part of the hemispheres
- Includes: nucleus caudatus, putamen, and globus pallidus
- Extensively connected to the striatum, substantia nigra compacta, and reticulate, and subtalamic nucleus
- It works via circuits between several components and other brain structures (such as the cortex, and spinal cord etc.)
- Similar to the cerebellum in that it is an accessory motor system and not directly incharge of motor activity
Major functions
- Behave as a variable filter
- 1) They match the performance specifications of motor programs to the criteria that have been established by the motivational and sensory cues that define a particular circumstance
- 2) They facilitate the selection of only those motor programmed that meet the specific criteria
- Participate in motor control only if incoming messages are facilitated with dopaminergic input from the substantia nigra compacta (loss = parkinson’s disease)
- Overall effect on motor activity is inhibition of inappropriate networks that link the motor cortex to the entire non-motor portion of the cerebral cortex
- Important for the selection of preparatory subprogramme tht move a limb or muscle from its initial position to one from which a standard motor program can continue (e.g. undoing a button); in Parkinson’s disease, the individual has impaired ability to perform preparatory movements and appears to freeze before executing major motor tasks
- The basal ganglia and cerebellum modulate the activity of motor system components for the respective selection and adjustment of movement
Limbic system:
The limbic system is a set of brain structures including the hippocampus, amygdala, anterior thalamic nuclei, and limbic cortex, which support a variety of functions including emotion, behavior, long term memory, and olfaction.
The following structures are, or have been considered to be, part of the limbic system:
• Amygdala: Involved in signaling the cortex of motivationally significant stimuli such as those related to reward and fear in addition to social functions such as mating.
• Hippocampus: Required for the formation of long-term memories and implicated in maintenance of cognitive maps for navigation.
• Parahippocampal gyrus:] Plays a role in the formation of spatial memory
• Cingulate gyrus: Autonomic functions regulating heart rate, blood pressure and cognitive and attentional processing
• Fornix: carries signals from the hippocampus to the mammillary bodies and septal nuclei.
• Hypothalamus: Regulates the autonomic nervous system via hormone production and release. Affects and regulates blood pressure, heart rate, hunger, thirst, sexual arousal, and the sleep/wake cycle
• Thalamus: The ""relay station"" to the cerebral cortex
In addition, these structures are sometimes also considered to be part of the limbic system:
• Mammillary body: Important for the formation of memory
• Pituitary gland: secretes hormones regulating homeostasis
• Dentate gyrus: thought to contribute to new memories and to regulate happiness.
• Entorhinal cortex and piriform cortex:[5] Receive smell input in the olfactory system.
• Fornicate gyrus: Region encompassing the cingulate, hippocampus, and parahippocampal gyrus
• Olfactory bulb: Olfactory sensory input
• Nucleus accumbens: Involved in reward, pleasure, and addiction
• Orbitofrontal cortex: Required for decision making
The limbic system operates by influencing the endocrine system and the autonomic nervous system. It is highly interconnected with the brain's pleasure center, which plays a role in sexual arousal and the ""high"" derived from certain recreational drugs. These responses are heavily modulated by dopaminergic projections from the limbic system.
The limbic system is also tightly connected to the prefrontal cortex. Some scientists contend that this connection is related to the pleasure obtained from solving problems. To cure severe emotional disorders, this connection was sometimes surgically severed, a procedure of psychosurgery, called a prefrontal lobotomy (this is actually a misnomer). Patients who underwent this procedure often became passive and lacked all motivation.
Amygdala – part of the limbic system.Involved in signaling the cortex of motivationally significant stimuli such as those related to reward and fear in addition to social functions such as mating.

"

Front 14

72.              Functions of cerebellum. Regulation of posture and movement.

Back 14

"Cerebellum
- Portion of the metencephalon
- Characterised by numerous folds on its surface
- Afferent fibres fall into 3 categories
- 1) Those that project into the archicerebellum: From the vestibular nucleus complex
- 2) Those that project into the paleocerebellum: From dorso and ventral spinocerebellar tracts and cuneate nucleus
- These fibres carry information concerning the activity of muscle and tendon stretch receptors
- Provide the paleocerebellum with the information needed to modulate various reflex activity
- 3) Those that project into the neocerebellum: From pontile and medullary structures
- Include pontile gray matter and reticular formation
- Supply information necessary for the modulation of voluntary motor activity
- Afferent fibres project into the cerebellum: Inform the cerebellum???
Functions:
- Subserving skeletal muscle motor mechanisms
- Maintenance of consciousness: subtle role
- Regulation of various autonomic motor activities
- Important part in the chain feedback connections which serve to control the coordination of locomotor activity
- Forms an integral part of the pyramidal and extrapyramidal motor systems

Posture and movement: regulation and system components
- The brainstem initiates a series of orders for movement which passes through to the muscles via the spinal cord
- This information also enters the cerebellum and feedback action on the spinal cord
- The cerebellum helps the brain plan the sequence of orders and also receives information on the speed and direction of movement via the vestibular apparatus
- The cerebellum calculates this information and predicts where all parts of the body will be in the next few milliseconds; this calculation step occurs in the vermis
- The basal ganglia help the motor cortex to execute the movement patterns and determines the timing and force of the movement
- The basal ganglia also help in the cognitive control of movement
- Pyramidal system: Consists of pyramid-shaped cells in the cortex and their efferent pathway is to skeletal muscle
- Extrapyramidal system includes all motor portions of the CNS not in the pyramidal system (basal ganglia, thalamus, and cortex)
- The cerebellum monitors various states of inertia and momentum of muscles via a feedback mechanism through which signals go to the cerebral cortex to make necessary adjustment
To summarise motor function, one can say that the extrapyramidal system maintains an organised background of muscle tone, posture, and gross movement upon which the pyramidal system can direct discrete and precise movements
"

Front 15

73.              Areas and functions of the cerebral cortex. Control of voluntary movements.

Back 15

"Association system in the cerebral cortex
- Association areas each contain different parts of the cerebral cortex
- Divides into 3 parts
1) Parieto-occipito-temporal association area
- Consists of parts of the somatic sensory cortex, visual cortex, and auditory cortex
- Function of this area:
- To provide coordination for the body in space
- Language comprehension via Wernick’s area
- Visual processing of language or reading
- Ability to name objects
2) Temproral
- Found in the rostral part; non-auditory portion of the frontal lobe
- Associated with mental and motor cortexes
- Functions of this area:
- Thought processes
- Motor and non-motor thinking
- Word formation
- Vocalisation
3) Limbic association area; Prefrontal or frontal association area
- Found in the rostral pole or the parietal lobe
- Part of the limbic system
- Functions of this area:
- Emotion
- Behaviour
- Motivation
- Important in the organisation of behavioural responses resulting in endocrine, visceral, and somatic motor activity

Movement:
- The brainstem initiates a series of orders for movement which passes through to the muscles via the spinal cord
- This information also enters the cerebellum and feedback action on the spinal cord
- The cerebellum helps the brain plan the sequence of orders and also receives information on the speed and direction of movement via the vestibular apparatus
- The cerebellum calculates this information and predicts where all parts of the body will be in the next few milliseconds; this calculation step occurs in the vermis
- The basal ganglia help the motor cortex to execute the movement patterns and determines the timing and force of the movement
- The basal ganglia also help in the cognitive control of movement
- Pyramidal system: Consists of pyramid-shaped cells in the cortex and their efferent pathway is to skeletal muscle
- Extrapyramidal system includes all motor portions of the CNS not in the pyramidal system (basal ganglia, thalamus, and cortex)
- The cerebellum monitors various states of inertia and momentum of muscles via a feedback mechanism through which signals go to the cerebral cortex to make necessary adjustment
- To summarise motor function, one can say that the extrapyramidal system maintains an organised background of muscle tone, posture, and gross movement upon which the pyramidal system can direct discrete and precise movements
"

Front 16

74.              Functions of the thalamus and reticular formation.

Back 16

"1) The thalamus is the largest area of the diencephalons
2) The function is to connect the fore-brain with the rest of the brain; i.e. a relay centre for the thalamus
3) Great sensory ganglion of the brain stem being interposed in the pathway from peripheral receptors and the cerebral cortex1
4) Contains many distinct clusters of nuclei that are topographically organised to receive input from select parts of the body and relay outputs to select parts of the cerebral cortex
5) Many, but not all, of these nuclei have sensory function
6) Observe both specific projection pathways (point to point) and non-specific projections systems
Anatomical formation:
7) Consists of 3 parts:
1) The epithalamus: Does not degenerate with fore-brain removal; contains the habenuar and paraventricular nuclei
2) Dorsal thalamus: degenerates after removal of the forebrain; contains the sensory relay; largest part of the thalamus grouped into medial, midline, and intralaminar complexes
3) Ventral thalamus: Partly degenerates with fore-brain removal

Reticular formation
1) Extends from the spinal cordmedullary junction throughout the length of the medulla, pons, and midbrain
2) Rostral to the midbrain, it is divided into the reticular formation of the thalamus (occupies the medial thalamus) and the reticular formation of the hypothalamus (comprises a portion of the lateral hypothalamus)
3) Consists of nerve fibres passing in all directions and is composed of nerve cells of different sizes and shapes (98 anatomic nuclear groups have been identified within)
4) Functionally supported by several networks:
5) Ascending networks: receives afferent signals from all systems including the spinal cord
6) Efferent fibers are formed into 3 groups:
7) Ascending fibres: project to other structures of the brain stem and cerebrum (form the ascending reticular formation)
8) Fibres projecting to the spinal cord
9) Fibres projecting to the cerebellum
Major function of descending reticular formation
10) Control of skeletal muscle motor activity
11) Control of cardiovascular, respiratory, and other autonomic activity (sleep)
12) Control of the activity within the sensory pathways of the CNS
"

Front 17

"75.              Physiology of sleep and alertness, rhythms. REM and non-REM sleep."

Back 17

"Sleep: A period of rest during which volition and consciousness are in partial or complete abeyance and the body functions are partially suspended; a behavioural state marked by characteristic immobile posture, and diminished but readily reversible sensitivity to external stimuli
Characteristics
- 1) Reduced ability to distinguish external stimuli
- 2) Increased threshold for stimuli
- 3) Decreased skeletal muscular activity and increased smooth muscle, visceral activity
- Needed for restoration of the nervous system
Alertness:


REM and non-REM sleep
Non-REM or slow wave sleep: characterised by HVSA EEG waves
1) Originates from deactivation of CNS from ARAS
2) Also known as deep sleep
3) Characterised by dreaming and descending waves that inhibit spinal motor neurons and cause postural atonia
REM sleep
4) Characterised by periods of EEG wave activity that is not synchronised (LVRA type)
5) Associated with rapid eye movement = REM or can be detected by myogram (i.e. movement of masseter muscle in animals)
6) Occurs periodically in animals
7) Function is not known but it may represent a primitive and ontogenetically older condition than slow-wave sleep
8) Theories as to function:
1) Serves as an endogenous source of stimulation to promote maturation
2) Needed to establish neuronal pathways serving binocular vision
3) Internal reward mechanism
4) Promotes consolidation of memories for recently learned events
5) Essential for maintaining emotional stability
6) Required for the maintenance of the norepinephrine and dopamine NT systems
Types of rhythms
1) EEG correlates to the behaviour and various states of consciousness and are describe based on variation in EEG voltage and frequency
2) In simplified terms, there are 2 types of EEG waves:
1) LVFA or low voltage, fast activity
1) Activated or arousal EEG
2) Associated with alert states
3) Also known as Desynchrony or desynchronised EEG
4) Thought to be due to the presumed desynchrony or neuronal generators
5) Constant firing of neurons creates an ongoing, low voltage pattern
2) HVSA or high voltage, slow activity
1) Deactivated EEG
2) Associated with sedated states (sleep or anesthesia)
3) Also known as synchronised EEG
4) Perhaps reflects the more synchronous charge of neurons resulting in less frequent, higher voltage activity
3) Theta rhythm
1) Reflects activity in some subcortical areas, especially the hippocampus
2) Occurs during alertness (LVFA)
3) Generally a very synchronous rhythm of 4 – 7 peaks per sec.
"

Front 18

76.              Signal transmission. Coding on receptors. Transmission of somatosensoric information – scheme.

Back 18

"Signal Transmission:
• Sensory cells are surrounded by tissues that modify the stimulus before it reaches them

• In the sensory cell's receptor membrane, the E in the stimulus is converted to electrical E in form of ion fluxes that change the membrane potential of the sensory cell, resulting in a receptor potential – transduction

• The information represented by the receptor potential is coded to yield a particular pattern of nerve impulses in the sensory nerve fibres
Coding on Receptors:
38. involves TRANSDUCTION – convert of stimulus E to generator potential - GP

39. On the level of neighbouring afferent nerve it involves TRANSFORMATION – transformation of GP to AP by summation of GP

40. CONDUCTION – AP wiring by nerve



Transmission of somatosensoric information


see book!








"

Front 19

77.              Autonomic nervous system. Antagonism and synergism effects. Cholinergic and adrenergic systems.

Back 19

"1) The autonomic system is divided into the sympathetic and parasympathetic systems
2) According to neurotransmitter release:
3) Both systems secrete ACh in pre-synaptic terminals
4) Parasympathetic post-synaptic ganglia secreate ACh
5) Sympathetic post-synaptic ganglia secrete norepinephrine
6) According to impulse transmission:
7) The ANS differs from the from the somatic system in that the motor neurons which come into immediate relationship with the effector (i.e. postganglionic neurons) lie outside the CNS

Sympathetic (Adrenergic?) division
1) Tends to act in a widespread manner to prepare the body for emergencies and vigorous muscular activity
2) Its mediators are norepinephrine and epinephrine
3) The medulla, upon stimulation, can support the sympathetic system by secretion of adrenaline (structurally similar to epinephrine) for circulatory effects
4) Prepares the body for “flight or fight”
5) Main actions:
6) Blood vessels: vasoconstriction
7) Bronchial muscle: relaxation
8) Stomach wall: relaxation
9) Sphincters: constriction
10) Blood vessels of abdomen: vasoconstriction
11) Small intestine and colon walls: relaxation
12) Urinary bladder: relaxation
13) Urinary sphincters: constriction
14) Genitalia: vasoconstriction
15) Sweat glands: secretion
16) Pupil dilation
17) Increased heart rate
18) Mobilisation of liver glycogen

Cholinergic or parasympathetic division of the ANS
1) Acts more discretely on individual organs or regions
2) When acting on the viscera, smooth muscle walls of the GIT undergo rhythmic contraction (peristaltic waves), the bile duct is relaxed, and secretions are increased
3) In general, the increase contractile activity and secretion
4) GIT blood flow is increased
5) Considering that anabolism is the constructive phase of metabolism, and nervous system process which stimulates food passage and absorption from the GIT can be labelled as the anabolic nervous system
6) Parasympathetic action (summary):
7) Bronchial muscle: constriction
8) GIT: peristaltic contraction
9) Sphincters: constriction
10) Blood vessels of abdomen: vasodilation
11) Urinary bladder: constriction
12) Urinary sphincters: relaxation
13) Genitalia: vasodilation
14) Slows heart rate
15) Increases salivary output

Antagonism and synergism of the ANS
The sympathetic and parasympathetic systems are not antagonistic to each other but functionally synergistic in balancing the bodies reactions. This is best demonstrated during erection in which the parasympathetic system is required for vasodilation of testicular arteries and the subsequent erection however it is the actions of the sympathetic system that control ejacualation.
Synergism: Sympathetic system synergism occurs with the stimulation of the adrenal gland to release into general circulation adrenaline

"

Front 20

"78.              Skeletal muscle – structure and function, contraction. "

Back 20

"Skeletal muscle
o Represents about 40% of the body mass
o Each muscle is composed of muscle fibres and each fibre consists of thousands of sarcomeres
o Sarcomere = the functional unit of skeletal muscle
o Consists of myosin (~1500) and actin (~3000) filaments
o Arranged side by side in the form of bands
o The actin filaments have the ability to slide on the myosin filaments
o I-band: solely actin filaments
o A-band: combination of actin and myosin filaments
o Z-disk: Point of connection between 2 sets of actin filaments
o Function of skeletal muscle: Skeletal muscle is responsible for all forms of voluntary movement of the animal body
o Mechanical properties
o Muscles contract by stimulation from motor nerves
o When the nerve action potential reaches the muscle, ACh is released which initiates action potential in the muscle fibre
o The action potential cause calcium release from the sarcoplasmic reticulum (SR)
o Calcium causes a conformational change in the sarcomere exposing a binding site for actin on the myosin fibre; acting then “walks along” the myosin fibre thereby causing sarcomere contraction
o Energy consuming process

Excitation-contraction coupling in skeletal muscle
1) A series of events involved in translation of an action potential on the sarcolemma into a muscle contraction
2) In summary, the events are:
? An action potential of the sarcolemma depolarises the transverse tubule (T-tubule) system of the muscle cell
? Depolarisation of the T-tubules induces the release of calcium from the SR
? The release of calcium binds Tn-C initiating alterations in Tn-I
? Alterations in Tn-I result in a movement of tropomysin relative to actin and myosin and remove stearic hindrance to their interaction
? Actin and myosin interact to form an actin-myosin complex that activates the myosin ATPase, releasing energy for muscle contraction and inducing a bending of the myosin molecules and the hinge region
? This action pulls the thin myofilaments and their associated Z-lines toward the centre of the sarcomere, resulting in muscle shortening


Summation of muscle contraction
1) Also called temporal summation of muscle contraction
2) Intensity of tension development by individual muscle fibres during contraction is proportional to the number of calcium Tn-C complexes formed during excitation
3) When skeletal muscles are stimulated to contract while still undergoing relaxation, a second muscle twitch is produced and develops a greater tension than the initial contraction
4) Observed when muscles are repeatedly stimulated to perform a series of contractions

"

Front 21

79.              Role of calcium ions in muscle contraction. Oxygen debt and its role in muscle function during excercise.

Back 21

"Calcium ions:
1) A series of events involved in translation of an action potential on the sarcolemma into a muscle contraction
2) Calcium is required to expose actin bind sites
3) In summary, the events are:
o An action potential of the sarcolemma depolarises the transverse tubule (T-tubule) system of the muscle cell
o Depolarisation of the T-tubules induces the release of calcium from the SR
o The release of calcium binds Tn-C initiating alterations in Tn-I
o Alterations in Tn-I result in a movement of tropomysin relative to actin and myosin and remove stearic hindrance to their interaction

Oxygen debt:
1) Heavy exercise causes the anaerobic conversion of muscular glycogen to lactic acid in the absence of oxygen
2) The necessity of heavy breathing associated after exercise is the allow for the aerobic breakdown of the said glycogen after the conversion of lactic acid
3) Required because hard exercise depletes oxygen stores of the body and they must be replenished
4) Combined with myoglobin, ~0.5l of oxygen is stored
"

Front 22

"80.              Function of motor unit, neuromuscular junction. "

Back 22

"Motor unit
o Includes the motor neuron, neuromuscular junction, and the myofibrils innervated by the muscular neuron
o Equal to a muscle fibre (and related structures) innervated by a single neuron fibre
o There can be 3 – 100s of muscle fibres per motor unit
o The fibres of the motor unit are not bound together but spread between fibres of other motor units; this formation helps the motor units support each other

Neuromuscular junction
o Also known as a motor end plate
o The point of junction of a nerve fibre with the muscle that it innervates
o It includes an area of folded sarcolemma of the muscle fibre and an axon terminal located in the folds and containing vesicles of the neurotransmitter acetylcholine (ACh)

Blocking of neuromuscular transmission
o The paralysis of the motor end plate
o Can be brought about by competitive binding of ACh receptors and thus preventing its activity, binding to axon terminals and preventing ACh release (as in the case of botulism)

"

Front 23

81.              Compare the smooth muscle with the skeletal muscle. Effects of acetylcholine and norepinephrine on the electrical and contractile activity of visceral smooth muscle.

Back 23

"Smooth versus skeletal muscle
o Mechanism of contraction: Same method in both muscles but smooth muscle contractions are generally slower and for a longer period of time than skeletal muscle contractions
o Cross bridge structure: Structural differences allow smooth muscle to require 1/10th – 1/300th because of slower cross bridge cycle
o Force of contraction: Higher in smooth muscle (4 – 6kg/cm2) than skeletal muscle (3 – 4kg/cm2)
o Shortening capabilities: Smooth muscle contraction can cause the fibres to shorten <2/3 the resting size; skeletal muscle can contract only 1/3 the resting size
o Latch mechanism: Feature of smooth muscle that allows for contraction maintenance and decrease energy requirements
o Stress-relaxation mechanism: Feature of smooth muscle that keeps the tension of the muscle even during length changes; important in hollow organs where pressure can changes suddenly

Effects of ACh and norepinephrine on smooth muscle
Ach is the post-synaptic NT of the parasympathetic system
Norepinephrine is the post-synaptic NT of the sympathetic system
Both Ach and Norepinephrine are antagonistic to each other and illicit opposite response when bound to tissue
Their effects on smooth muscle depend on the type of receptor it contains
Sympathetic action:
Blood vessels: vasoconstriction Bronchial muscle: relaxation
Stomach wall: relaxation Sphincters: constriction
Blood vessels of abdomen: vasoconstriction Small intestine and colon walls: relaxation
Urinary bladder: relaxation Urinary sphincters: constriction
Genitalia: vasoconstriction
Parasympathetic action:
Bronchial muscle: constriction GIT: peristaltic contraction
Sphincters: constriction Blood vessels of abdomen: vasodilation
Urinary bladder: constriction Urinary sphincters: relaxation
Genitalia: vasodilation
"

Front 24

82.              Adequate and inadequate stimuli. Sensory receptors.

Back 24

"Adequate stimulus: The particular form of energy to which a receptor is most sensitive; Stimulus able to illicit a sense response; e.g. gentle touch that stimulates surface mechanoreceptors
Inadequate stimulus: The energy form or stimulus is such that the receptor is not sensitive to it and therefore unable to illicit a response; e.g. extreme/intense touch of surface mechanoreceptors fails to illicit a response and instead is interpreted as pain. Inadequate stimulus = pain
? Adequate and inadequate stimuli are dependent on both quantity and quality of the energy form

Senses:
5) There are 5 senses:
1) Vision
2) Taste
3) Hearing and equilibrium
4) Smell
5) Taste
Classification of senses:
o Based on their primary receptors (mechanoreceptors, photoreceptors, chemoreceptors, etc.)
o Based on where they are processed in the brain
o Internal vs external senses
o Evolutionary origin
o Presence of teloreceptors (hering and vision)

"

Front 25

"83.              Pain – division, characteristics, role of endorphins. Control mechanisms. "

Back 25

"Pain: A feeling of distress, suffering, or agony caused by stimulation of specialised nerve endings. Its purpose is chiefly protective; it acts as a warning that tissues are being damaged and induces the sufferer to remove or withdrawl from the source
The sharp sensation of pain is the flight or escape reflex
The continous ache is to prove protection of the damage tissue and to prevent further injury to the surrounding tissues


Referred pain: Pain felt in an area distant from the site of pathology but not mediated through a common innervation. There is no evidence that referred pain occurs in animals but it seems likely. E.g. visceral pain that is translated by the brain as surface pain

Superficial, deep, and visceral pain
o Superficial pain: Pain response as detected by surface or skin receptors. The skin records stimuli as pressure, vibration, touch, cold, warmth. Medianoreceptors: skin receptors, merkel’s disks; they detect pressure, touch, vibration, weight. Efferent nerves transfer the stimulus. Deeper in the skin: there are meisner, Valter-paccinian, rafin, Kraus receptors which are sensitive to other stimuli than medianoreceptors. Nerve fibres transfer the stimulus
o Deep pain: Pain response as detected by receptors found in deeper tissues such as periosteum, joint surfaces, arterial walls, falx and tentorium of the cavum cranii.
o The superficial and deep senses create the somatovisceral senses (receptors are located in muscle, ligaments, and joints)
o Visceral pain: Pain response as detected by receptors located in the viscera. GIT pain receptors are located in the mucous membrane and are similar to surface receptors. The mucosa is quite sensitive to irritation and other painful stimuli. Parenchyma of the liver is almost insensitive to pain but the bile ducts are very sensitive; Causes by spasm of the hollow viscus; ischemia (local lack of blood due to torsion, blockage, accumulation of nutritional end products that results in tissue necrosis).
Most pain receptors respond to one of 3 types of stimuli:
1) Mechanical stress and trauma
2) Extremes of heat and cold or thermoreceptors: consist of warm and cold receptors; the greater the temperature deviates from “normal” the impulse transfer frequency is increased
3) Chemical substance (including but not limited to histamine, K+, prostaglandins, bradykinins, and ACh)

Pain control system (analgesic) in brain and spinal cord: The variability in pain threshold among individuals is due to the brains ability to regulate pain levels. This is known as the analgesic system and consists of:
1) Periaquaductal gray area = mesencephalon
2) Raphe magnus nucles (found in the medulla)
3) Dorsal horns of the spinal cord-spinal pain inhibitory complex
At these points the analgesia signals can block the pain signals from reaching the brain
The periventricular nucleus of the hypothalamic also shows pain blockage but it is not complete
Transmitters in the analgesia system include serotonin and enkephalin

Endorphins and pain sensation
Endorphins are naturally occurring peptides that have opiate-like activities but are not derived from opium
Includes enkephalins and endorphins
- Enkephalins: 2 naturally occurring forms (methionine enkephalin and leucine enkephalin); belong with endorphins; also act as neurotransmitters
- Endorphins: “endogenous morphine”; raise the pain threshold, produce sedation, and euphoria; produced naturally at neural synapses at points in the CNS pathway where they modulate the transmission of pain perception; ?-endorphin is found in the hypothalamus and hypophysis; dynorphin is a pain killer.
Exert effects by interacting with opiate receptors of cell membranes
"

Front 26

84.              Functions of various parts of the visual system.

Back 26

"Vision involves:
1) Focusing of electromagnetic radiation by the cornea and crystalline lens of the eye onto the photoreceptors of the retina
2) Conversion by the photoreceptors of radiation into 450 – 700nm wavelength range in action potential
3) Interpretation of the spatial relationship of incoming light waves

Parts of the visual system:
a) Lens: changes the focal length by changing its curvature in a process known as accommodation.
b) Iris: contriction of the iris narrows the pupil and restricts incident light to the central portion of the lens
c) Anterior hemisphere: Cornea through which light enter the eye
d) Posterior hemisohere: sclera (protection), choroids (nutrition), retina (receptor)
e) Retina: Most sensitive part of the eye. Contains rods (black and white vision; night vision) and cones (colour vision). Light (electromagnetic radiation) causes excitation of the rods and cones which transmit signals to neurons in the retina itself and from there to the optic nerve
f) Macula: Adapted region for bright and sharp vision. Its central part contains only cones and is called the fovea; most external part and allows for direct passage of light
Extra
Pathway of the visual system:
1) Involves decussation of the signals from the medial aspects of the retina
2) Light ? lens ? corpus vitreum ? retina ? inner side of retina ? ganglion cells ? plexiform layer ? nuclear layer ? limiting membrane ? cones are rods (outer side of retina) ? optic nerve
3) Optic disk ? stimulus ? optic chiasma (combines the signals from the second eye and create the optic tracts ? corpus geniculatics laterodorsalis ? fissure calcanicus in cerebral cortex which is considered the primary visual cortex
4) Fibres also go to more posterior areas in the cortex, such as: hypothalamus, pretectal nuclei (there is a reflex located here translated to eye movement), superior canaliculus (adapted for fast eye movement) and ventral lateral nucleus geniculatus
5) The newer pathway is responsible for colour analysis
6) Primary visual cortex: found in the occipital lobe in the area of the fissure calanina. Most signals are read in this area; especially from the macula and signals from the periphery of the retina.
7) Layers:
8) Neurons which carry the signal reach the cortex and end in different layers (6 layers total). The signal spreads to deeper and superficial layers. Colour “blobs” are spread in the layers to receive the signals and react to colour.
9) Secondary visual cortex: The signals pass to additional areas for analysis

"

Front 27

85.              Neural pathways that transmit visual information from retina to cerebral cortex. Dark adaptation and visual acuity.

Back 27

"o Optic disk ? stimulus ? optic chiasma (combines the signals from the second eye and create the optic tracts ? corpus geniculatics laterodorsalis ? fissure calcanicus in cerebral cortex which is considered the primary visual cortex


Visual acuity: Ability to visually distinguish between objects
Visual acuity test: Performed by walking an animal through an obstacle course or unfamiliar environment. Animals with good visual acuity will manoeuvre around obstacles (i.e. not run into them)

Dark adaptation
1) Ability of some species to see in environments with very low light (darkness)
2) Brought about by adaptations to the visual receptors including:
3) Tapetum lucedum:
4) Part of choroids containing crystalline rods that act as a light reflecting area
5) Blue-green, red, or yellow
6) Eyes with tapetum have characteristic iridescence and can see in greater darkness
7) Summation: used by photoreceptors to ensure signal firing
"

Front 28

"86.              Functions of various parts of the ear. Conduction of sound, types. Nerve pathways from the inner ear to the auditory cortex."

Back 28

"The auditory system functions for the reception of airborne or waterborne vibratory energy
• Bone conduction – sound sets the skull in vibration that is directly conducted to the cochlea
• Air conduction – transmission of sound waves through the air to the organ of hearing via:
– the external ear
– the auditory canal terminated at the tympanic membrane
(eardrum)


Nervous processes and pathway:
• Receptor cells are contained within a highly organised structure known as the organ of Corti
• Sound enters the external auditory meatus ? encounters the tympanic membrane ? the membrane vibrates ? the vibration is transferred to the 3 bones of the ear (anvil, hammer, and stirrups) ? vibration is transferred to the internal ear or cochlea
• The oval window separates the air and fluid of the internal ear
• Vibration of the fluid of the internal ear ? basilar membrane ? sensory stimulus ? action potential ? firing of the auditory (cochlear) nerve ? medulla ? cochler nuclei ? caudal colliculi ? auditory cortex
• Secondary areas of hearing surround the primary acoustic cortex; they are responsible for analysis of voice and comparison with tones from memory; affect attention
• The auditory cortex lies principally on the supratemporal plane of the superior temporal gyrus but it also extends over the lateral border of the temporal lobe
• In the central part of the primary cortex there is a distinction between high and low frequencies and the ability to ignore certain sounds/voices
• Damage to the secondary areas of hearing will cause, in humans, the ability to hear but will prevent the understanding of meaning of words

Structure and function of the auditory cortex
1. The acoustic pathway must cross at least 4 nuclei: cochlea nuclei ? inferior colliculi ? medial geniculate bodies ? auditory receiving area of the cortex
2. In the cortex, it is located at the ectosylvian gyrus in the temporal lobe
3. Basal region stimulation of the cochlea (high tones) stimulates the most forward regions of the auditory cortex; apical regions project to the caudal part
4. The primary auditory cortex receives an orderly projection from the median geniculate and therefore from the cochlea
5. Function: To process the wave stimuli into a comprehensible understanding of sound

"

Front 29

87.              Functions of the various parts of the stathokinetic organ. Vestibulo-ocular reflex.

Back 29

"The non-hearing portion of the internal ear consists of a set of ducts containing fluid = semicircular canal
Also called labyrinth or vestibular system
The functions of the vestibular apparatus:
Responsible and most important for equilibrium and spatial orientation
Nervous stimuli of the CNS to activate muscles to prevent falling
Eye movement: During head movement, it stabilised the eye in space thereby decreasing the movement of fixed object on the retina surface
The function of the semicircular canal is responsible for angular acceleration and angular velocity
The otoliths are responsible for linear acceleration or the gravity acceleration (g); also connected to the eyes and helps to orient in space

Vestibulo-ocular reflex
Relatively simple reflex action controlling eye movement
Designed to provide a stable visual field as the head is turned
Rotation of the head is sensed in the vestibular system
The purpose of this system is to maintain a stable visual image on the retina during head movements
The set point in this case is the retinal activity generated by the visual system
The cerebellum functions as the error-detection and rest mechanism
Summary of the components:
Vestibular receptor ? vestibulocochlear nerve ? vestibular nuclei ? occulomotor nucleus ? eye movement
Horizontal optokinetic nystagmus
A rhythmic, physiological movement of the eyes in response to a moving visual field
E.g. looking at telephone poles from a moving car
This reflex involves visual input as the primary sensory regulator
The purpose of the reflex is to provide a fixed visual image on the retina during a slow movement of the eyes in the direction opposite to that of body movement
Nystagmus
A periodic, rhythmic, involuntary movement of both eyeballs in unison
There is a slow component in one direction and a quick return
The movement may be vertical, horizontal, or rotary
Common causes are lesions cerebellum or vestibular apparatus or increased intracranial pressure
Vestibular nystagmus: Occurs when the semicircular canals are continuously stimulated
Postrotational nystagmus: Occurs at the end of rotation due to inertial endolymph flow
Any stimulation of the endolymph can serve to excite the semicircular canal receptors (e.g. flushing the external ear with warm water) and cause nystagmus

"

Front 30

88.              Neural pathways of olfactory information from the olfactory mucous membrane to the cerebral cortex. Taste pathways. Functions of the vomeronasal organ.

Back 30

"Olfactory pathway
1) The olfactory receptors in the nasal cavity send axons into the olfactory nerve that end in the secondary olfactory centres of the olfactory bulb
2) The fibres pass to the anterior part of the piriform lobe of the cerebral cortex and to parts of the amygdaloid nuclear complex.
3) The olfactory pathway is distinct in that it by-passes the thalamus

Taste pathways
1) In the oral cavity, the taste of food via its chemical composition (in man they are sweet, salty, bitter, and sour) causes receptor firing
2) In the thalamus, taste receptors project to an area in the ventrobasal complex, medial to the area for touch and temperature receptors
3) In the cerebral cortex, the taste area is medial to the end of the face area in the somatosensory receiving area; bilateral removal of this area leads to taste discrimination impairment

Smell and taste
1) The two senses are linked in that the integration of taste sensations requires to additional input of smell, touch/texture, and temperature
2) The importance of taste is apparent during illness when the nasal cavity (and consequently sense of smell) is blocked: we can no longer detect the taste of food as strongly (if at all)

Olfaction and sexual behaviour
1) the main and accessory olfactory systems play an important role in regulation of reproduction
2) Animals are commonly attracted to and sexually stimulated by chemical signals from members of the opposite sex
3) The sources of these scents are many fold and include gland secretions and urine
4) Commonly known as pheromones
5) Olfactory signals are long lasting and frequently used to mark territory (“marking” or spraying with urine)
6) In most species, olfactory clues are used in conjunction with tactile, visual, and auditory signals
Domestication may have decreased the specificity of response to chemical stimuli

Vomero-nasal organ:
The vomeronasal organ (VNO) is a complex of different structures that forward specific chemical signals commonly called pheromones to the central nervous system. In some macrosmatic animals, e.g. rodents, the VNO consists of vomeronasal receptor neurons located in a sensory epithelium of the vomeronasal duct, their afferent axons connecting the duct with the accessory olfactory bulb, associated glands and ganglionic cells in the nasal septal mucosa. The organ’s main task is to influence mating and social behavior.
"

Front 31

89.              Neuronal interactions. Classification of reflexes. Monosynaptic and polysynaptic reflexes.

Back 31

"5 patterns of neuronal interactions:
– Divergence spreads stimulation to many neurons or neuronal pools in the CNS.
– Convergence brings input from many sources to a single neuron.
– Serial processing moves information in a single line.
– Parallel processing moves the same information along several paths simultaneously.
– Reverberation is a positive feedback mechanism which continues to function until actively inhibited.


• Reflexes may be classified in 4 ways:
– 1. How the reflex was developed:
– 2. The nature of the resulting motor response
– 3. The complexity of the neural circuit involved:
– 4. The site of information processing:
• 1. How the reflex was developed:
– Innate reflexes are the basic neural reflexes a person is born with.
– Acquired reflexes are rapid, automatic, learned motor patterns.
• 2. The nature of the resulting motor response:
– Somatic reflexes provide involuntary control of the nervous system.
• a. superficial reflexes of the skin or mucous membranes
• b. stretch reflexes (deep tendon reflexes) such as the patellar reflex
– Visceral reflexes (autonomic reflexes) control systems other than the muscular system.
• 3. The complexity of the neural circuit involved:
– In a monosynaptic reflex, a sensory neuron synapses directly onto a motor neuron.
– A polysynaptic reflex has at least 1 interneuron between the sensory neuron and the motor neuron.
• 4. The site of information processing:
– In spinal reflexes, processing occurs in the spinal cord.
– In cranial reflexes, processing occurs in the brain.


Monosynaptic reflex: 1 stimuli results in 1 reflex being activated
Polysynaptic reflex: 1 stimuli results in >1 reflex being activated
Reflex arcs are composed of 5 elements:
1) A receptor organ
2) Afferent neuron
3) Interneurons in the spinal cord or brain
4) Efferent neuron
5) Effector organ
Polysynaptic reflexes contain all 5 elements
Monosynaptic reflexes are missing element #3 (interneurons)
"

Front 32

"90.              Define hormone, neurotransmitter, and neuromodulator tissue hormone. Hormone production and secretion. General regulation of hormone secretion."

Back 32

"Hormone: A chemical transmitter, produced by cells of the body, and transported by the bloodstream (and other means) to the cells and organs which carry specific receptors for the hormone and on which it has a specific regulatory effect. Divided into 2 classes based on solubility, target cell receptors, and mechanism of action.
Neurotransmitter: A substance (norepinephrine, acetylcholine, dopamine) that is released from the axon terminal or a presynaptic neuron on excitation, and which travels across the synaptic cleft to either excite or inhibit the target cell.
Neuromodulator tissue hormone: Polypeptides of various length that may be associated with neuronal tissues but exert changes of neuronal activity. A substance which causes changes in the activity of the target cell for a long period of time. For example, stimulation for the secretion of protein kinases, resulting in the reduction of the number of surface receptors and modulating the function of the synapse.
Pheromone: A substance secreted to the outside of the body and perceived (by smell) by other individuals of the same species, releasing specific behaviour in the recipient. For example, pheromones secreted by the Queen in a hive to suppress the development of female genital organs of its workers.

Hormone production:
- Hormones fall under many different classes including steroids (cortisol, estrogen, testosterone), amines (epinephrine, serotonin, dopamine, histamine) and peptides (somatostatin, enkephalin, thyroid-regulating hormone)
- Usually synthesised in the RER as prohormone and occasionally preprohormone, which are inactive forms of the hormones
Hormone secretion:
- Secretion is directly into the circulating blood
- Occurs due to appropriate cell stimulation
Hormone secretion regulation:
- Virtually all control systems are regulated, at least in part, by feedback loops
- Negative feedback: most common; the target cell response inhibits the regulating signal (e.g. ACTH stimulation for the secretion of cortisol; free cortisol in circulation inhibits the adenohypopheseal secretion of ACTH)
- Positive feedback: generally regarded as a “runaway” process in that the target cell stimulates the regulating signal. It is important for Leutinising hormone (LH) maintenance
- Secretion of hormone precursors as a general regulatory process
- Antagonistic action of common hormones in homeostasis (e.g. insulin and glucagon)
"

Front 33

91.              General mechanisms of hormone effects. Transport of hormones. Hormone receptors.

Back 33

"In the course of circulation, hormone molecules encounter receptor molecules located on the surface of the target cell
These receptors are hormone specific
The binding action of the hormone initiates in the target cells a series of steps (cascades) that influence one or more aspects of metabolism or functions of those cells
Only cells that contain free receptors are affected by the hormone

4 principal concepts of hormone action
1) Kinetic effects
- Include pigment migration, muscle contraction, and glandular secretion
2) Metabolic effects
- Consists mainly of changes in the rate and balance of reactions and concentrations of tissue constituents
3) Morphogenetic effects
- Have to do with growth and differentiation of tissues, organs, and systems
4) Behavioural effects
- Result from hormone influences on the functioning of the nervous system
Note: Hormones have multiple effects and some hormones can demonstrate >2 classes of effect/action (e.g. thyroid hormone having metabolic and morphogenetic effects)
"

Front 34

"92.              Neurosecretory process. Hypothalamus, regulation, hormones, and their functions."

Back 34

"Neurosecretion:
- Neurosecretory cells: Special class of neurons that produce hormones and secrete them into the bloodstream
- Little structural difference between neurosecretory cells and an ordinary nerve cell
o The release of hormone from the terminal of a neurosecretory cells is the equivalent to neurotransmitter release from a nerve cell
o Observe morphological differences
- Hormones are produced in the cell body and transported by centrifugation (within the axon) towards the terminal
- Transport has been determined to be <2800mm/day

Hypothalamus
- Part of the CNS, lying under the thalamus and the 3rd ventricle
- Main pattern of hypothalamic function is: stimulus ? integration ? response
- Connected to the limbic system, midbrain, tegmentum, pons, and hindbrain
Temperature regulation:
- Afferent signals include cutaneous receptors and temperature sensitive cells in the hypothalamus
Thirst
- Efferent stimulation being:
o Electrolyte and osmotic pressure imbalance (rise in ECF sodium)
o Stretch receptors in the major vessels (a decrease in stretch or a lower venous blood return stimulates thirst) and renin releasing cells of the kidney (which also detect a drop in arterial pressure)
- Stimulation of the hypothalamus triggers thirst and the release of anti-diuretic hormone (ADH)
- A drop of arterial pressure causes the release of renin ? angiotensin I ? angiotensin II system, which stimulates thirst as well
Fever
- Efferent stimulation being:
- Endotoxin ? inflammation ? polymorphonuclear leukocytes, monocytes, macrophages ? with endogenous pyrogens ? stimulation of hypothalamus
- Stimulation occurs at the preoptic area of the hypothalamus
- In combination with prostaglandins, results in fever
"

Front 35

93.              Hypothalamus-pituitary unit. Hormone transmission from the hypothalamus to adenohypophysis and neurohypophysis.

Back 35

"Posterior pituitary gland: Endocrine functions
- The posterior pituitary gland function occurs by the synthesis of 2 hormones
- These hormones are synthesised in the cell bodies of the neurons in the supraoptic and paraventricular nuclei and transported down their axons to the posterior pituitary
- These hormones are oxytocin and arginine-vasopressin-antidiuretic hormone (ADH)
o Stored in the form of bound polypeptides or neurophysins (contain oxytocin or vasopressin, ATP, and neurophysin)
o Hormone release is a calcium dependent process
o Stimulation of the posterior lobe results in degranulation
Link with the hypothalamus
- Magnocellular neurons in the supraoptic and paraventricular nuclei
- About ½ are oxytocin neurons having been isolated due to their activation by suckling
- The remaining neurons react to antibodies against ADH
- These neurons fire during hypovolemia (high plasma osmolarity) to stimulate ADH release and increase water uptake by the kidney

Summary
Oxytocin:
o Release is stimulated by suckling and parturition
o Acts on the mammary gland: milk ejection
o Acts on the uterus: Uterine smooth muscle contraction
ADH
o Release is stimulated by high plasma osmolarity, hypovolemia
o Acts on the kidney to increase renal tubular resorption of water

o Discuss the hypothalamo-adenohypophyseal relationships
Functional anatomy
- The hypophysis is connected to the hypothalamus by the infundibulum ( a connective stalk)
- The hypophysis is generally divided into 2 parts:
o Neurophypophysis: origin in neural ectoderm
o Adenohypophysis: origin in oral ectoderm; more anterior
- The hypophysis is also known as the pituitary gland

Relationship
- The hypothalamus and hypophysis share a common circulation: the portal hypophyseal vessels
- Arterial blood enters the pituitary gland through the dorsal and ventral hypophyseal arteries
- The dorsal artery endsin capillary plexuses in the median eminence and pituitary stalk
- The ventral and dorsal parts receive blood from “long” portal vessels
- The “short” portal vessels drain into the capillary network
- This hypophyseal portal system is the route by which the hypothalamic regulating hormones enter and control the secretion of the adenohypophyseal hormones
- Anterior hypophyseal hormones are believed to induce negative feeback on hypothalamic secretions
Summary: The anterior pituitary secretes 6 hormones and secretion is controlled by chemical messengers carried in the portal hypophyseal vessels from the hypothalamus to the pituitary. These substances have generally been referred to as releasing (libertine) and inhibiting (statin) hormones

Recommended Name Abbreviation Recommended Name Abbreviation
Corticoliberin CRH Prolactostatin PIH
Somatoliberin SRH Somatostatin STS
Melanoliberin MRH Melanostatin MIH
Folliberin FSH-RH
Luliberin LH-RH
Thyroliberin TRH Tyreostatin
"

Front 36

"94.              Hormones secreted by pituitary gland, their functions. "

Back 36

"Anterior lobe hormones that act directly on the soma:
1) Somatotripic hormone or growth hormone (STH):
- Structurally similar to prolacting (common origin?)
- Undergoes rapid metabolism by the liver (T1/2 20 – 30min)
- STH is secreted during times of low blood glucose, stress, high protein food intake, increased sleep, dopamine receptor agonists; arginine has an STH releasing effect
- STH inhibition occurs during: REM sleep, high blood glucose, cortisol, free fatty acids, and medroxyprogesterone
- Effects of STH most obvious in bone (acts on growth plates), cartilage, muscle, kidney, and liver
- STH acts via somatomedians (insulin-like growth factors) such that it can induce lactation
- Effects on metabolism: causes increased retention of protein nitrogen by the body; increases cell permeability to amino acids; affects carbohydrate metabolism such that it can cause diabetes mellitus
2) Prolactin:
- Promotes growth of mammary tissue
- Stimulates and sustains milk production
- Release is stimulated by suckling
- Also known as lactogenic hormone, luteotropic hormone, LTH, and mammotropic

Anterior lobe hormones that stimulate other endocrine glands to release a hormone
3) Thyrotropic hormone:
- Also known as TSH
- Glycoprotein
- Acts to increase the activity of chief cells in the thyroid gland by:
o Increasing iodine uptake
o Production and release of thyroxin
o Proteolysis of thyroglobulin
4) Adenocorticotropic hormone or ACTH
- Peptide (39 amino acids long with the first 29 being highly conserved across the species)
- Stimulates secretions of the adrenal gland
- Stimulates the release of glucocorticoids (mineralcorticoids to a lesser degree); aldosterone in birds
- Very short half-life (T1/2 = 6min)
5) Gonadotropic hormone
- Related to the reproductive organs of both sexes
- Includes luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
- See question 125

"

Front 37

95.              Functions of hypophyseal and extrahypophyseal gonadotropins. Neuroendocrine regulation of reproductive activity in male and female.

Back 37

"Hypophyseal gonadotropins:
1) Follicle-stimulating hormone (FSH)
- Release is under hypothalamic control
- Feedback control by gonadal hormones
- Functions:
o Helps maintain spermatogenic epithelium in the male
o Responsible for early growth of ovarian follicles in females (rising oestrogen levels likely depress GnRH then FSH output); FSH in hypophysectomised animals causes multiple follicle growth without oestrogen productions or ovulation)
2) Luteinizing hormone (LH) or interstial cell stimulating hormone (ICSH)
- Glycoprotein chemically different among the species; T1/2 30minutes
- Output is dependent on GnRH
- Normal effects (female):
o Stimulate the developing follicle towards maturation
o Oestrogen production
o Ovulation
- Normal effects (male)
o Acts on Leydig cells, causing testosterone production

Extrahypophyseal gonadotropins
3) Pregnant mare serum gonadotropin (PMSG)
- Found in the blood of the pregnant mare between days 40 and 140
- Activity is like pituitary FSH
- Also shares activity with LH
- In the mare, it does not pass renal filter and consequently has a very long period of action
o Maternal ovaries: Causes follicular development and finally multiple ovulations in the pregnant animal; end result is the formation of multiple corpora lutea
- Use in medicine is to stimulate follicular growth in inactivated ovaries
4) Human chorionic gonadotropin (HCG)
- Similar to LTH because they both have lactogenic properties
- Little prolactin release apart from during pregnancy and lactation

Regulation
- Largely through negative feedback loops
- Lack of gonadotropins causes atrophy of the sex cells (testis, ovaries)
"

Front 38

"96.              Sexual differentiation in animals, stages, and hormonal regulation. "

Back 38

"4 stages of sex (gender) genesis:
1. Chromosomal (combination of sexchromosomes determines the direction of differentiation of indiferent basis)
bisexual origin
– indifferent basis – 2 undifferentiated gonads with urogenital sinus:
• 2 pairs Wolfian ducts
• 2 pairs Müllerian ducts


2. Gonadal (differentiation of gonads)
Sex differentiation – direction is determined by genetical sex
– time asymetry – ? gonads are differentiated later

In order for the ? characteristics to develop, the testes must produce testosterone
If testosterone is not produced ? ? characteristics


3. Somatic (differentiation of excretory ducts)
Male:
– the excretory ducts from kidneys of the embryo = Wolfian ducts, channel the spermatozoa away from the testes

– active secretion of testosterone by fetal testes ? development of ? accessory structures – epididymis, spermatic ducts
– they grow into testes – connection with the system of tubules – rete testis – collection of spermatozoa from the seminiferous tubules

– in the tissue of the external genitalia
testosterone ? dihydrotestosterone
– sinus urogenitalis ? penis, accessory sex glands, closure of urethra
– supports the formation of the scrotum

– Mullerian ducts undergo involution
Female:
passive differentiation (lack of testosterone) ? oviducts, uterus, vagina

– Wolfian ducts undergo involution
– sinus urogenitalis ? vulva – vestibulum, labia


4. Physical (attainment of sex maturity, formation of sex dimorfism, specific signs of sex behavior)
"

Front 39

97.              Development of the brain in males and females. Sexual maturation. Primary and secondary sexual characteristics.

Back 39

"• The surge center is not active in the male (testosterone)
• Testosterone must be converted to E2 in brain tissue before it inactivates the surge center
• The surge center does not undergo involution in females (E2 is bound to ?-fetoprotein) – it cannot cross the blood-brain barrier
Sexual maturation:
• Complete formation of extragenital sexual dimorfism and a specific sexual behavior begins by the sexual maturation = development of the generative and hormonal activity of the gonads and ability of reproduction

• Factors:
• – breed (genetic characteristics)
• – feeding
• – geographic and climatic conditions
• – breeding manners
• – social factors

• It is not suitable to mate females immediately after reaching the sexual maturation!

• Differentiation of ? and ? :
– primary sex characteristics (gonads)
– secondary sex characteristics
– morphological
– functional
– behavioral
Puberty:
= the period of life when sexual activity commences and the animal becomes able to reproduce

• Cyclic activity of the gonads is initiated in both genders

• The reproductive organs gradually achieve their adult size and shape

• Sex hormones produced in the gonads cause the development of the secondary sex characteristics and arouse the sex drive of both sexes

• Specific characteristics of sexual behavior


"

Front 40

"98.              Growth hormone, effects, regulation pathways. "

Back 40

"Growth hormone (GH) is a peptide hormone. It stimulates growth and cell reproduction in humans and other animals. It is a 191-amino acid, single chain polypeptide hormone that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. Somatotrophin refers to the growth hormone produced natively in animals.
Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up). Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells.
Increased height during childhood is the most widely known effect of GH
In addition to increasing height in children and adolescents, growth hormone has many other effects on the body:
• Increases calcium retention, and strengthens and increases the mineralization of bone
• Increases muscle mass through sarcomere hyperplasia
• Promotes lipolysis
• Increases protein synthesis
• Stimulates the growth of all internal organs excluding the brain
• Plays a role in fuel homeostasis
• Reduces liver uptake of glucose
• Promotes gluconeogenesis in the liver[13]
• It contributes to the maintenance and function of pancreatic islets
• It stimulates the immune system
Regulation
Peptides released by neurosecretory nuclei of the hypothalamus (Growth hormone releasing hormone and somatostatin) into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotropes. However, although the balance of these stimulating and inhibiting peptides determines GH release, this balance is affected by many physiological stimulators (e.g exercise, nutrition, sleep) and inhibitors of GH secretion (e.g. Free fatty acids). [3]
Stimulators of GH secretion include:
• growth hormone releasing hormone (GHRH) from the arcuate nucleus
• ghrelin
• sleep
• exercise (in particular resistance training)
• low levels of blood sugar (hypoglycemia)
• Short-term fasting
• dietary protein
• increased androgen secretion during puberty (in males from testis and in females from adrenal cortex)
• arginine[4]
Inhibitors of GH secretion include:
• somatostatin from the periventricular nucleus
• circulating concentrations of GH and IGF-1 (negative feedback on the pituitary and hypothalamus)[2]
• hyperglycemia
• glucocorticoids
• estradiol or any estrogen
"

Front 41

"99.              Growth and development - definition, stages. "

Back 41

"Growth: = an increased body weight until mature size
• Increased cell size
• Increased cell number
• Increased muscle, bone, and CT
• Organs are mature
Development = coordination of all bodily processes to obtain maturity
• Cell growth
• Cell differentiation
• Changes in body shape and form
Stages:
1. prenatal period: preimplantation; embryo; foetus
2. postnatal period: neonatal; suckling; weaning, puberty; maturity; senescence

• Three phases of prenatal development:
1. Sex cells
2. Embryonic stage
3. Fetal stage
• Early development:
1. Head is larger that the body
2. Limbs develop
3. Tissue Growth
4. CNS development
5. Organ development

Postnatal Development:
• Growth is via hypertrophy
• Muscle Fiber Type
– Red Red and White
• Body shape is still disproportioned
• BW = 5 – 7% mature weight
• Distal limbs are more developed than proximal limbs
– Leg length is ~ 60% of mature leg length
"

Front 42

"100.          Growth and development - regulation, growth curves."

Back 42

"see book
Growth Regulation – other hormones:
not all understood:
Insulin
Thyroid hormones
Glucocorticoids
Sex steroids and prolactin
Effects of hormones on food intake (CCK, NPY, leptin)
"

Front 43

"101.          Thyroid and parathyroid glands, hormones, their actions. Regulation of Ca metabolism. "

Back 43

"Outline the principal pathways by which thyroid hormones are metabolised. List the main actions of thyroid hormones, and outline their principal regulatory scheme
Metabolism:
- Thyroid hormones are synthesised by the addition of iodine to thyrosine to yield the hormone thyroxin. The result is active thyroid hormone in 2 forms:
o Triodothyronine or T3
o Thyroxine or T4 (most common)
- Thyroid hormone synthesis requires large amounts of iodine and it is actively transported from dietary intake (active transport process because it goes against the concentration gradient)
- Synthesis of thyroxine is under the control of the pituitary gland:
- Thyrotropic hormone or TSH
- Glycoprotein
- Acts to increase the activity of chief cells in the thyroid gland by:
o Increasing iodine uptake
o Production and release of thyroxin
o Proteolysis of thyroglobulin
- Fate of thyroid hormone in the body:
- T3 and T4 are distributed to almost every tissue of the body
- Skeletal muscle and the liver and major extravascular extrathyroidal stores
- Metabolic conversion of T3/T4 can occur by 3 methods:
1) Deiodination by 5’-deiodinase and 5-deiodinase
2) Deamination (alone or in conjunction with oxidation or decarboxylation)
3) Glucuronide or sulphate conjugation
- Not every tissue can use all 3 methods to convert T3/T4

Main actions
1) Thermogenesis and increased oxygen consumption
- Best known function
- Stimulates metabolic rate, mitochondrial activity, etc. and heat production
- Observe increased heart rate
2) Nerve and muscle
- Stimulation makes animals nervous, irritable, and hyperactive
- Increases spontaneous electrical activity in the brain
- Decreases threshold of sensitivity to a variety of stimuli
- Muscle is affected at both high (observe higher catabolism) and low (observe hypotonus) levels of thyroid hormone
3) Interaction with catecholamines
- Relationship between T3/T4 and epinephrine
- Thyroid hormone increases the lipolytic effect if epinephrine
4) Effects on metabolic enzymes
- Observe increased utilisation of carbon hydrates, protein catabolism, and greater oxidation of fats
- Deficiency is marked by high serum cholesterol

Regulation
- Under direct control of the adenohypophysis via TSH
- TSH release is controlled by tyreostatin from the hypothalamus
- Negative feedback from thyroxin (end-product) and the tyreotrophic complex
- Hypothalamus contains thyreasatin-synthase, which generates tyreostatin; temperature sensitive (released during cold temperatures) to release thyreostatin
- Lack of iodine as a pathological control mechanism

Describe the biosynthesis and metabolism of parathyroid hormone. Describe the action of parathyroid hormone, identify the source of calcitonin and its principal action. Summarise the effects of hormones on calcium metabolism
Functional anatomy
- The parathyroid gland consists of 2 pairs in most species
- Located in the anterior cervical region of the thyroid

Parathyroid hormone:
- Origin in the need to protect against hypocalcaemia and the need to maintain the skeletal integrity in terrestrial animals
- Hypocalcaemia most prevalent in regions of relatively low calcium and high phosphorous
- Hormone: parathormone
o Synthesised as a prohormone
o PTH release is inversely related to Ca++ levels in plasma (high blood plasma levels = rapid decrease in PTH and vice versa)
o Blood phosphorous concentrations do not affect PTH release
- Function:
o Stimulates osteoclasts to resorb bone Ca++
o Bone matrix is destroyed to metabolise Ca++ from skeletal reserves into the ECF
o PTH also stimulates osteoblasts to repair bone minerals
o GIT: Increases Ca++ absorption from the GIT in the presence of vit D-calciferol
o Kidney: Reduces tubular resorption of phosphorous

Thyreocalcitonin or calcitonin:
- Produced in the parafollicular cells of the thyroid gland C-cells
- Target cells of calcitonin include bone, kidney, and intestine (lesser degree)
- Inhibits bony readsorption of calcium and decreases entry of clcium from the skeleton into blood plasma
- Also induces hypophosphatemia due to direct, increased rate of movement of phosphorous out of plasma into soft tissue and bone; also inhibits bone phosphor resorption
- Renal action: induces phosphaturia
- Calcitonin is secreted in response to a high calcium meal

Calcium metabolism:
- Calcium comprises 2% of body weight with 90% found in bone and 1% in body fluids
- In plasma, calcium exists in an ionised form (50%), complexed with anions (10%), and bound to plasma proteins (40%)
- Calcium balance is obtained by the continual intake and loss of calcium
- Calcium is shifted between 5 compartments:
6) ECG
7) ICF
8) Bone
9) GIT
10) Kidney
- This shift is brought about by the actions/influence of:
a) Vitamin D
11) Calcitonin
"

Front 44

"102.          Adrenal gland. Hormones secreted by cortex and medulla, their actions, regulation pathways. "

Back 44

"Adrenal glands
- Functional anatomy
o The adrenal gland is associated with the kidney (located cranially to it)
o Consists of 2 layers: outer cortex and inner medulla
o Although the cortex and medulla are connected to form the adrenal gland, they are functionally, embryologically, and morphologically separate tissues
- Endocrine functions:
- Secretions are very diverse in effects
- Adrenal medulla
o Originates from the neural crest
o Products are amines in nature
o Effects are similar to postganglionic sympathetic neurotransmitter
o Products are produced by chromaffin cells and are not essential for life
o Theory: If the sympathetic nervous system remains in tact these products are not necessary but act as a system reinforcement
o Secretions are continuous (tonus theory) but increase rapidly and to a high degree during an emergency (“fight-or-flight” theory)
- Adrenal cortex
o Originates from the mesodermal coelomic epithelium (i.e. same origin as the gonads)
o Products are steroids in nature
o Exert primary activity on carbohydrate and electrolyte metabolism

Adrenal medulla hormones
- Known as catecholamines
- Adrenaline and noradrenaline are the main products
- Synthesised by a thyrosine pathway
- Secreted in response to acetylcholine release by the preganglionic sympathetic nerve terminals in the medulla
- Generally released in response to emergency
- Adrenaline: Responsible for metabolic effects
o Increases cardiac output
o Increases blood glucose (induces breakdown of glycogen stores in the liver; breakdown of muscle glycogen; stimulating ACTH output to increase adrenal cortex glucocorticoid release and thereby indirectly stimulate gluconeogenesis
o Effects on adipose tissue: induces free fatty acid release
- Noradrenaline: Responsible for circulatory effects
o Increases peripheral resistance
- Both hormones increase heart rate and systolic blood pressure

Adrenal cortex
- Site of production of >50 steroids but only several are primary
- Divided into 3 functional groups:
1) Glucocorticoids
- Include cortisol, corticosterone, cortisone
- Main influence in carbohydrate and protein metabolism
- Increase influence on gluconeogenesis
o Decrease peripheral utilisation of glucose
o Antagonistic to insulin
o Increase protein catabolism
o Reduce fat stores
- Antiinflammatory effects:
o Reduce circulating lymphocytes, eosinophils and fix lymphocytic tissue
o Reduce the degree of local inflammatory processes
o Inhibit ACTH output by depressing corticoliberin output
o As a result of these effects, are used as SAIDS (e.g. prednisone)
2) Mineralcorticoids
- Include deoxycorticosterone and aldosterone
- Cause an increase n Na+ reabsorption from the primary urine, sweat, saliva, and gastric juice
- In other words, they cause sodium retention in the ECF
- Kidney: act on the distal tubule and collecting duct; Na+ is retained at the expense of K+
- Indirect result of sodium retention is water retention
- Excess mineralcorticoid production may result in oedema from excess ECF fluid
- Controlled by the renin-angiotensin system such that angiotensin II formation stimulates the brain and consequently aldosterone release
3) Adrenal sex hormones
- Includes the synthesis of small amounts of androgenic and estrogenic steroids
- Function under normal secretion is unknown but may be problematic in hyperplastic conditions (e.g. masculinizing adrenocortical hyperplasia)
- Theory: Adrenal sex hormones provide male and females with small amounts of the sex hormones that are not produced by their respective gonadal tissues. In other words, adrenal sex hormones provide females with small quantities of testosterone and males with small quantities of estrogens. Essential for normal function???

Mammalian foetal adrenal cortex
- Cortisol secretions from the foetal adrenal cortex act upon the placenta to reduce progesterone and increase estrogen
- This in turn promotes the release of prostaglandin F2? and uterine contractions are stimulated
- Results: the foetus influences the onset of parturition


"

Front 45

103.          Pancreatic hormones and their role in glucose metabolism.

Back 45

"• Pancreatic hormones and their role in glucose metabolism.

- Regulation of blood glucose is brought about by hormone secretions from the Islets of Langerhans in the pancreas
- 2 main hormones responsible for regulation of carbohydrate metabolism: insulin and glucagon
Insulin
- Secreted from beta ells
- Species differences as to its structure (i.e. it is not a highly conserved hormone)
- Based on symptoms of pancreatectomy (diabetus mellitus with early symptoms of inability to use glucose for energy production or fat or glycogen synthesis), the mechanism of action is at the level of glucose utilisation; nerve tissue and RBCs do not require insulin for glucose metabolism
- Biological effects of insulin:
o Stimulates anabolism of carbohydrates, fats, proteins, and nucleic acids from their respective building blocks (monosaccharide, fatty acids, amino acids, and mononucleotides)
o Binds to surface receptors and may help the glucose transport process
o Principal effect: allows for glucose transport across the cell membrane
- Hormone of the fed state
- Insulin deficiency
o The ability of the peripheral tissues to use glucose for oxidation or (in the case of the liver and muscle) for the synthesis of glycogen is greatly impaired
o Observe: hyperglycaemia
o Excess glucose is excreted by the kidney are results in loss of water and electrolytes
o Complications from lack of insulin (diabetus mellitus) include metabolic acidosis, peripheral circulatory collapse from dehydration, cellular dehydration, coma and death
- Insulin surplus
o As insulin favours the removal of glucose from blood (by glucose oxidation, glycogen deposition, and lipogenesis), hypersecretion of insulin causes glucose to be cleared from the blood at an increased rate
o Observe: hypoglycaemia
o Symptoms include incoordination, muscular weakness, tremors, unconsciousness, and convulsions

Glucagon
- Produced by alpha cells of the pancreatic Islets
- The effect of glucagon are opposite to those of insulin
- Mode of action:
o Increases activity of liver dephosphorylase kinase, which activates phosphorylase
o Phosphorylase favous glyvogenolysis and thereby increases blood glucose
o Also stimulates gluconeogenesis
o Effects are similar to epinephrine
o Released during hypoglycaemia
- Over or under production of glucagon has not been reported in domestic animals

Diabetus mellitus
- The condition caused by an absolute or relative lack of insulin
- Has been reported in all domestic species but most common in cats and dogs
- Herbivorous animals are more resistant and can live for longer periods without insulin

"

Front 46

104.          Functions of pineal gland and thymus. Functions of melatonin.

Back 46

"Pineal gland
- Also known as epiphysis cerebri
- Important neuroendocrine structure (second to the hypothalamus) in the relay of neural and endocrine regulatory pathways
- Regulatory functions include:
a. Gonadal function
b. Adrenal function
c. Thyroid function
d. Immunodefence function
e. Control of cell/organism aging
f. Sleep and other biological rhythms
- In other words: the pineal gland serves as a transducer, transforming many forms of external and internal signals into hormonal signals including light, magnetic field, specific and unspecific stress induced stimuli
- Easily penetrated by large molecules from blood
- Main secretory hormone is melatonin
- Melatonin:
o Main function is linked to reproduction in relaying the effects of the ambient photoperiod through the 24hrs pattern (well established phenomena in sheep)
o Known as the photoperiod-pineal-hypothalamic relay
o Summary: the pineal gland receives signal from the retina; the suprachiasmatic nucleus functions as an internal biological clock regulating circadian rhythms; the culmination of melatonin production during night/darkness; production is higher during the winter than summer

Thymus
- Unique organ in that it is large in newborns, reaches its apex of development at puberty, then declines in activity thereafter
- Studies have demonstrated the thymus is essential for normal development
- Thymectomy in mice at birth induces wasting disease
- Wasting disease can be prevented by implant of thymus tissue even when the tissue is such that the exit of cells is impaired
- Conclusion: Thymic hormone(s) is(are) present which is(are) essential for normal development
- These actions are not directly related to immune function of the thymus


"

Front 47

"105.          Oestrogens and progestins - functions, their production and secretion. "

Back 47

"
Estrogen
- In competition with progesterone
- Regulated by corticoids; levels are effected by stress
- Brings about changes in the genital tract
- Isolated from ovaries, adrenal glands, and male testes
- In cycling females, it is produced by the theca cells of the growing follicle under the influence of FSH and LH; estrogen production by these cells in influenced by changes in vascularisation
- Estragol: unlocks prolactin inhibition before parturition to allow for mammary tissue development
- Additional effects: Important in ruminants because of the protein anabolic effect; inhibits growth of bones and favours ossification of the epiphyseal lines
- Functions:
o Epitheliotropic hormone: Vasostimulation and general health of the skin are observed
o Mitogenic hormone
o Induced vaginal cornification
o High doses: inhibits pituitary output of gonadotropins by blocking Gn-RH output; low doses favour FSH and LH release
o Myotropic effect: Sensitises the myometrium to become responsive to oxytocin
- Effects
o Associated with estrus: hypermia, water and salt transudation, and hypertrophy
o = Oedema of the reproductive tract
o Secondary sex characteristics!
Progesterone
- Regulated by corticoids; levels are effected by stress
- Functions:
o Acts on the uterus to cause quietening of the myometrium
o Influences unlocking of prolactin inhibition before parturition to allow for mammary tissue development
o At large doses, inhibits Gn-RH release
o May be responsible for controlling the duration of estrus (as soon as the follicles fail to produce progesterone, there is a FSH burst which stimulates follicular development and proestrus)
o Acts with estrogen to bring about psychic estrus or sexual receptivity
o May be responsible for silent heat (its lack from the previous follicle fails to show signs of sexual receptivity)
o Influences mammary gland development
o Acts on the endometrium to inhibit mymetrial activity and prepare for implantation
o Inhibits T-cells responsible for tissue rejection and thus help in the maintenance of early pregnancy

Puberty signals the onset of periodic hypothalamo-adenohypophysio-gonadal hormonal processes, with signals of interest in sexual activity. In both sexes, triggering of pubertal hypothalamic activity implicates input from the amygdala, olfactory bulb and pineal gland. Due to seasonal activity, there is also seasonal potential for reproductive activity.
Females at puberty: develop a hypothalamic gonadostat, in order to reach an adequate and sufficiently mature state that allows gonadotropins to increase, and allows generation of requisite cyclical endocrine pulses (especially the pro-estrous phase) and surges of GnRH, LH, FSH, PRL.
Males at puberty: signalled by the production and ejaculation of fertile spermatozoa and by sexual desire. The secretory productivity of the accessory reproductive glands appears to predict spermatogenesis. The functioning of spermatogenesis follows gradual maturation of the hypothalamic gonadostat. Males produce only pulsatile synthesis of releasing and gonadotrophic hormones.
"

Front 48

106.          Anabolic and sex functions of androgenes. Regulation of testosterone secretion.

Back 48

"Androgens: Any steroid hormone which promotes male characteristics. The 2 main androgens are androstenedione and testosterone
Functions:
- The endocrine control of the testes is via GnRH which stimulates secretion of LH and FSH
- LH stimulates the Leydig cells to produce testosterone, which suppresses GnRH (negative feedback)
- FSH stimulates the Sertoli cells, including increasing the secretion of Androgen-Binding Protein (ABP), and the conversion of androgens to oestrogens, and secretion of Inhibin (which has negative feedback on FSH secretion).
- High FSH levels in a male suggests a reduction in the spermatogenic process.
- Male behaviour (and characteristic aggressiveness)
Testosterone:
- Leydig cells produce testosterone
- Required in high levels for spermatogenesis, and especially for the meotic process
- It is readily intravascularly, creating and maintaining libido, secretions of the male accessory organs, and development of “male” features, e.g. increased muscle mass.
- Sertoli cells converts testosterone into Dihydrotestosterone, an androgen more biologically potent than testosterone.
- ABP binds androgens within the adluminal compartment – this may provide stability for local androgen concentrations.
- Androgens are associated with higher blood pressures and thus must influence blood pressure.
- Androgens are also important in foetal and placental development
o Androgens in primates are transported to the placenta, where they are converted to oestrogen.
o A similar process occurs in the horse, except that they are converted in the foetal gonads.
Testosterone (TTN):
- Secreted by the Leydig cells, which is under the control of LH.
- LH secretion is controlled by episodic release of GnRH. The number of episodes varies from 4 to 12 per 24 hours, according to the domestic species. This pathway is essential for the secretion of testosterone.
- Testosterone then moves from the interstitium around the Leydig cell, into the blood, lymph and seminiferous tubules.
- The presence of Sex-Hormone Binding Globulin (a protein) is vital for the transport and secretion of TTN (without this, production reduces drastically).
- High levels of TTN cause a negative feedback effect by inhibition of LH secretion. However, high concentrations of intratesticular TTN are vital for spermatogenesis
Importance:
- TTN is important for the development and maintenance of the secretory epithelium of the accessory sex organs, and for development of the general male body characteristics.
"

Front 49

107.          Functions of testes. Spermatogenesis and its hormonal regulation. Function of scrotum in spermatogenesis. Role of epididymis in sperm maturation.

Back 49

"The functions are the production of spermatozoa, testosterone (and other androgens) and testradiol (and other steroids).

It all begins in the walls of the seminiferous tubules, which are lined with spermatogonia. These undergo mitosis. Each time, one remains, one undergoes further division. The number of divisions is species-specific, but between 3 and 5 in the domestic species. At the end of this, they are known as primary spermatocytes. They then enter the first prophase of meiosis (development may be arrested here) (DNA is synthesised throughout the last mitotic division), and they enter a haploid state, and become secondary spermatocytes. (At this point, though haploid, a further division is still required as the chromasomes replicate at the start of meiosis). After the second division in meiosis, they become Spermatids.

The third and final step is their maturation into spermatozoa (spermiogenesis). This involves; 1. Formation of the tail, 2. Development of mitochondria for energy production, 3. Development of an organelle (acrosome) 4. Consolidation of structure (i.e. sperm need to be as compact as possible)
A large amount of cytoplasm is extruded during spermatogenesis. Spermiogenesis also starts in the seminiferous tubules, but finishes in the epididymus. The process of spermatogenesis involves cloning of a large number of spermatogonia. Cell losses occur though at all stages. Additionally, cells within a clone are not identical, due to meotic chiasma formation, thus genetic variability is increased despite their common ancestral source. A cycle occurs at the same cell sites in the tubules, at regular intervals, usually 8-16 days in domestic species, according to species. Spermatogenesis typically takes about times the time period of this cycle. This is coordinated in a spermatogenic wave (cycle) along the tubules.

Sertoli cells are important for controlling the development of germ cells, in regard to both their nutritive and regulatory function. During their maturation, they leave the basal compartment, through junctions of the Sertoli cells, into the central compartments of the tubules. On maturation, they leave the Sertoli cell and are free in the lumen. The Sertoli cell is thought to be the main source of fluid. The number of Sertoli cells remains relatively constant.

Hormonal control is via the Leydig cells, outside the tubules (in the interstitium) with some input from the Sertoli cells. The main function of the Leydig cells is the production of testosterone, vital for the development and maintenance of spermatogenesis and male characteristics, and controlled by LH.

The secretory activity of the Sertoli cell is controlled by FSH, and it may convert TTN to oestrogens. The functions of oestrogens in spermatogenesis is not known. The Sertoli cell also synthesises Androgen-Binding Protein, which assists in the regulation of TTN, and synthesises Inhibin, which suppresses FSH at the pituitary gland.

The epididymus is vital for both maturation and storage. The spermatozoa are not actively mobile, nor penetrative, until they have passed through (they gain the presence of “forward motility protein” and the activation of the acrosome, as they pass through). The epididymal function is dependent on TTN, or it will rapidly degrade. The seminal plasma is ionically balanced, nutritive, and acts as a pH-buffer. It consists mainly of fructose (and in some species inositol), together with small amounts of numerous minerals, solutes, PGs, etc.

Function of scrotum in Spermatogenesis?
"

Front 50

108.          Role of accessory sex glands in sperm motility. Components of semen and their functions. Process of capacitation. Fertilization.

Back 50

"Semen is the general name for the ejaculate of sperm and seminal fluid.
- Sperm contain DNA, proteins, mitochondria and cytoplasm.
- Seminal fluid is mostly fructose and water, and small amounts of minerals, solutes, prostaglandins, etc.
o It is ionically balanced, nutritive and a pH buffer.
o Fructose is the key component in that of the bull, ram, goat and rabbit.
o Others may have sorbitol (a precursor of fructose), and/or insitol, in the boar and occasionally found in bull/ram/stallion.
o The boar also has large amounts of ergothionine (a sulphur-containing base) and ascorbic acid (both anti-oxidants), citric acid, amino acids, proteins, sodium, potassium, lipids, phosphorylcholine, PGs, enzymes, zinc and anti-agglutinin.

Acrosome:
- Function is to penetrate the Zona Pellucida by dissolving a hole in the mucoprotein coat of the ovum.
- The acrosome contains hyaluronidase and acrosin.
- Assistance from the tail is also very important at this stage.
- This process initiates the Zona Reaction, which prevents any further spermatozoa from penetrating the zona pellucida (it has been shown to happen in about 1-2% of fertilisations in domestic animals).
o Penetration of additional spermatozoa = polyspermy

Capacitation
- Occurs after spermatozoa are deposited in the female tract, during which time they must undergo some changes
- Requires several hours.
o Glycoproteins from the seminal plasma or epididymal fluid are removed from the sperm surfaces
o Hydrolytic enzymes are activated in the acrosome. This allows the “acrosome reaction” to occur
- The acrosome reaction occurs ONLY in capacitated spermatozoa, and thus is considered by some to be part of the process of capacitation.

Accessory sex glands:

release secretion that is mixed with spermatozoa during ejaculation and makes essential part of the ejaculate – seminal plasma

• PROSTATE GLAND
• VESICULAR GLANDS
• BULBOURETHRAL GLANDS
• AMPULLAR GLANDS




Fertilization:
• Takes place in the oviduct

• Spermatozoa maintain their fertilizing ability for about 48 hrs

• Oocytes are ready for fertilization at the time of ovulation (they lose their ability to be fertilized about 24 hrs later)

Important steps in the fertilization process are:

1. Penetration of corona radiata
2. Binding of the spermatozoon to the zona pellucida
3. Release of enzymes from the acrosome of the spermatozoon (acrosomal reaction)
4. Penetration of the zona pellucida and binding to the oocyte membrane
5. Transfer of the spermatozoon´s nucleus to the oocyte
6. Blocking of penetration of additional spermatozoa (polyspermy)




"

Front 51

"109.          Functions of penis. Mating behaviour, neurohumoral regulation of copulation – scheme. Differences in dog mating. "

Back 51

"The penis has two key functions
1) Urination
2) Reproduction: enabling the transfer of sexual material to the female without dessication, through erection and ejaculation.
- The penis is fibro-elastic in the bull, ram and boar: there is very little cavernous or spongy space in the penis; increased pressure increases firmness, and the straightening of the sigmoid flexure provides the length necessary to copulate.
- In the stallion, cat and dog, the penis is vascular: becomes engorged with blood, increasing its size and stiffness during erection.
- In the cat, the female’s ovulation relies upon vaginal stimulation, which partly explains the male cat’s penile spines.

Copulation
- Defined as the act of sexual intercourse
- Reproductive behaviour varies greatly among different species.
- pre-coital auditory, olfactory, visual and tactile cues concur to coordinate critical dynamic conjunction of the two sexes.
- Sensory nerves are stimulated as the erect/elongated penis is inserted (intromission occurs) into the mucus-lubricated peripheral organs of the female genital tract, and copulation culminates with ejaculation.
- Copulation includes:
o Mounting
o Intromission
o Ejaculation
o post- ejaculatory/copulatory phases (especially in the boar, cat, dog and human).
- In boars for example, the sow’s olfactory response is that of the rigidity reflex, which greatly improves the possibility of the boar to mount. The receptive female stands or crouches immobile, allowing the male to mount her dorsally and from the rear.
- The initial attraction is provided by pheromones, which are especially important in normally solitary animals. There is also use of the vomero-nasal organ in some species.
- The endocrinology involves corticoids, adrenalin, and the parasympathetic nervous system and blood pressure.
- Courtship may include lip-curling, smelling, urinating, licking, and ear-twitching. In rodents and goats, there is a marked influence by male pheromones, also recorded in mice.

Erection:
- Controlled by the autonomic nervous system (specifically under parasympathetic control)
- Accomplished by the synergy of two mechanisms
1) Sexual excitement leads to the corpus cavernosum and corpus spongiosum becoming engorged with blood by arterial dilation and venule contraction.
2) The ischiocavernosus and bulbospongiosus muscles increase their tone, and occlude venous return (including by pressing the penile dorsal vein against the ischiadic arch. Pressures may increase to more than 15 000 mm Hg.
- The extent of expansion is proportional to the capacity of corpus cavernosum.
o In ruminant and boars, expansion is restricted as the penis is mostly fibro-elastic, and extension is more due to relaxation of the m.retractor penis to allow straightening of the sigmoid flexure.
o Expansion due to the corpus cavernosum is most noticeable in the horse.

Ejaculation
- Under sympathetic nervous system control
- The ejection of semen via the excretory ducts.
- This mostly occurs via stimulation of sensory nerves in the glans penis.
- Stimulation triggers a series of peristaltic contractions of the muscular walls of the epididymus, vas deferens and urethra, that move the spermatozoa from the accessory glands, through ducts, to the external urethral orifice.
o In the bull and ram, the sperm are mixed almost instantaneously with fluids from the accessory glands, in the urethra.
o In the stallon, boar and dog, sperm is mixed sequentially with fluids from the accessory glands, there sequential ejaculations are sperm-free, sperm-rich and sperm-poor respectively.
- Ejaculation is effected by the sympathetic fibres of the hypogastric nerves and plexus.
- At the end, sympathetic nerve stimuli cause vaso-constriction, detumescence and/or retraction.
- The motility of sperm ranges from 16 hours (bull), to 264 hours (dogs). Sperm are phagocytosed if still in the uterus after 2-3 days, except in mares.
Mating Behaviour?




Differences in dog mating?





"

Front 52

"110.          Functions of the ovary. Folliculogenesis, its neuroendocrine regulation. "

Back 52

"Ovary
- The female gonad; equivalent to the male testes
- The sex glands responsible for ova formation and from which the sex hormones (estrogen and progesterone) are released
- Small round body varying in size according to species and stage in reproductive cycle
- Outer membrane may be nodular or follicular in shape due to the ongoing rupture and release of ova
- Histologically, layers of the ovary:
- Outer layer: Zona parenchymatosa
- Central layer: Zona vasculosa
- Epithelium is simple cuboidal or epithelial = germinitive layer


- Folliculogenesis is the cyclic ovarian activity that commences at puberty

Neural control of Folliculogenesis
:
- The term puberty is used to define the onset of reproductive life and, for the female, the initiation of cyclic ovarian activity
- Usually associated with the appearance of estrus but also includes the events that immediately precede the onset of ovarian activity
- As studied in sheep:
- Birth – 7/8th month:
o Hypothalamic secretion of gonadotropins is very sensitive to negative feedback inhibition by estrogen
o Under these conditions, follicles are not able to develop
- At the 7th/8th month: 2 events occur that allow for the establishment of the ovarian cycle:
o 1) A decrease in hypothalamic sensitivity to estrogen induced negative feedback; GnRH pulsatile release from the hypothalamus increases and gonadotropins begin to be secreted in large amounts to the point that follicles are stimulated for development
o 2) Increased estrogen results in positive feedback stimulation of the hypothalamus and anterior pituitary with a resultant discharge of gonadotropins. This surge does not cause ovulation but does increase progesterone levels. This phase is short lived and is followed by an LH surge and subsequent ovulation
- The role of FSH in unclear

"

Front 53

"111.          Two-cell, two-gonadotropin concept of the ovarian steroid hormone synthesis. Follicular atresia. "

Back 53

"The theca interna is capable of synthesizing some steroid hormones, but not until the follicle has grown to the kate secondary or tertiary stage. Beginning at this time, the theca interna glandular cells synthesize andostenedione, which then diffuses into the membrane granulosa. The granulose calle convert this weak androgen to testosterone, and then convert the testosterone to estradiol. The estradiol synthesized in granulosa cells diffuse into the theca, where it enters blood vessels that transport it to target tissues in other parts of the body. Thus, estrogen synthesis in the follicle depends on the coordinatinated biochemical activity of two types of cells: thecal cells and granulosa cells.
In summary, cholesterol precursors are removed from the bloodstream by thecal cells. The metab olic machinery of these cells is specialized to synthesize androgens. Androgens produced by thecal cells diffuse to the granulosa. Subsequently, granulosa cells, which cannot produce their own androgens, use these adrogens as a precursor for conversion to estrogens.

Follicular atresia
= follicles stop developing and undergo involution
"

Front 54

"112.          Ovulation, its neurohumoral regulation. Formation of corpus luteum. Spontaneus and provoked ovulators."

Back 54

"Ovulation:
- Rupture of mature ovarian follicle on the surface of the ovary
- Factors of follicle rupture include:
o Increase in internal pressure of the follicular fluid
o Enzymatic changes
o Hyperaemia
o Contraction of smooth muscle fibres of the hilus
- A few follicles leave the primordial state each day, and begin to develop; one proceeds to ovulation. The others undergo destruction
- Which of the follicles proceeds is highly proportional to the timing of the regression of the corpus luteum
- There is a LH hormone surge about 24hrs before ovulation:
1) LH blocks the ooyte inhibitors, and meiosis I occurs
2) Endocrine changes lead to progesterone being secreted (instead of the androgens being converted to oestrogens), and granulosa changes are made to the luteal structure.
3) An increase in production of prostaglandins, leads to the release of proteolytic enzymes, reducing the ground substance and causing the dissolution of the follicular capsule and release of the oocyte.

Neuro-hormonal mechanisms of its control
- The hypothalamo-pituitary system develops without hormonal stimuli.
- Gamete production occurs in the embryo, such that the maximum number of oocytes are present at birthMeiosis is initiated by factors from the rete ovarii, but arrested at the dictyotene (resting) stage, until puberty.
- Control of the re-establishment of the growth and redevelopment of the primordial follicle is not fully understood, but it is independent of Gonadotropin influence.
- The oocyte increases in size, activity, and production of RNA and ribosomes. Follicular cells divide and grow into granulosa cells. At the end of the hormone-independent stage, receptors for FSH, oestrogen and CH are synthesised. FSH influences oestrogen production, and oestrogens increase the development of granulosa. The whole system is coordinated by the production of various inhibitors.

Corpus luteum
- Found in the ovary
- Secretes progesterone after the ovum is matured and released.
- It regresses quickly if there is no pregnancy, and a new follicle develops.
- If the corpus luteum doesn’t rupture, a pathological condition occurs, and there are no new follicles or cycles/heats.
- Creates an LH surge pre-ovulation.
- This converts granulosa from oestrogen to progesterone secretion, often the driving force for the formation and initial maintenance of the corpus luteum.
- PGF2? induces regression, causing luteolysis, and a drop in progesterone secretion.
- Thus the two produce the cyclical messengers


Spontaneous ovulation
- Includes dog, cow, goat, horse, pig and primates
- Ovulation occurs spontaneously after normal follicle growth, due to oestrogen secretion, causing an LH-release surge.

Provoked ovulation
- Include the cat, rabbit, ferret, mink and camelidae family; these require copulation for ovulation to be induced
- Vaginal stimulation leads within minutes to the ovulatory release of LH via spinal cord sensory pathways
- Hypothlamic and pituitary priming are prerequisites (occurs via high levels of estrogen)

"

Front 55

113.          Luteolysis. Differences in PGF 2alpha control of lutolysis in cow and mare. Relationship of oxytocin and PGF 2alpha in the luteolysis.

Back 55

"Luteolysis is the structural and functional degradation of the corpus luteum (CL) that occurs at the end of the luteal phase of both the estrous and menstrual cycles in the absence of pregnancy. In domestic animals, luteolysis is inititated by the hormones prostaglandin-F2alpha and oxytocin.
Diff in cow and mare:
Luteolysis:
• uterus required
• hysterectomy prevents luteolysis
• transplant ovary to neck - prevents luteolysis
• uterus needed for luteolysis and must be near ovary to have effect
• PGF is luteolysin
• counter current exchange between uterine vein and ovarian artery – present in cow, ewe, sow
– not present in mare
• PGF gets to ovary after going through the general circulation
• mare ovary is more sensitive to PGF than other species



PGF2? in luteolysis
- In sheep, oxytocin also stimulates uterine PGF2? synthesis and release. The ovine CL synthesises and stores oxytocin during the oestrous cycle. Thus a PGF2? pulse leads to a drop in Progesterone, and an increase in oxytocin release
- The corpus luteus is richly vascularised; PGF2? vasoconstriction is one pathway to causing luteolysis
- PGF2? binding sites develop on the luteal cells, which interferes with LH binding
- Spontaneous prolongation of the corpus leuteum may occur, due to a failure of the endometrium (uterus) to synthesise PGF2? at the proper time
"

Front 56

"114.          Functions of the oviducts, uterus, uterine cervix, and vagina. "

Back 56

"Uterus
- Hollow, muscular organ in which the ovum embeds itself, to be nourished during its development.
- It consist of: horn(s), body(s), cervix(s).
- It has 2 linings: mucus membrane (the endometrium) and a muscular layer (the myometrium).
- It requires some priming by progesterone before PGF2? can be synthesised to nurture and provide nutrients for the developing foetus.
Oviducts
- Passages through which the ova leaves the ovary to the uterus
- Also known as the uterine tube(s) and salpinx
- Only the left is functional in birds.
- Provide muscular contractions, nutrients, hormones, androgens and quiescence essential for foetal development
- Uterine cervix



- Vagina:
"

Front 57

"115.          Timing of the estrous cycles in various animal species. Phases of the estrous cycle, changes in reproductive tract during the estrous cycle. Estrous behaviour in domestic animals. "

Back 57

"The oestrous cycle represents the cyclical events of the hypothalamo-pituitaro-ovarian hormonal status changes.
The phases are:
1) Pro-estrus/Oestrous/Metestrous/Diestrous (anestrous): the follicular part of the estrus cycle, and is characterised by hypothalamo-adenohypophyseal pulses of GnRH, FSH and LH, maximum size of the follicle, secretion of the epithelium in the oviduct, uterus, cervix and vagina, and pheromone production
2) Estrus: most specific phase, and is characterised by zero day of the estrus cycle, ovulation, sexual receptivity
3) Metestrus the short post-ovulatory phases of the cycle, showing early luteal function, organisation of the corpus haemorrhagicum and its production of progesterones, oxytocin and inhibin. Oestrogen production decreases to a minimum, vaginal smears contain many leukocytes, with some non-cornified cells, and in heifers, some RBCs also may occur in endometrial bleeding.
4) Diestrus or anestrus: constitutes the major or longest part of the cycle, during which the corpus luteum secretes progesterone and oxytocin. Progesterone is much higher in this phase. In cows, ewes and sows, folliculogenesis may also occur during this phase. Diestrus of the unmated bitch, and of the mated but unfertilised rabbit or queen is especially remarkable and is termed pseudopregnancy

The follicle is the principal steroid-generating unit of the ovary. Its output is a function of the actions of its two types of somatic cells, the theca and granulosa cells. Their differences are a result of different hormone receptors in or on their cell membranes.

These cells are primarily controlled by FSH and LH, but with many secondary intra-ovarian influences or modulators, mainly steroidal by-products or end-products of the same cells.

Negative feedback:
- Increased levels of estrogen and decreased levels of progesterone mark the growth of new follicles (lack of progesterone removes estrogen synthesis inhibitions
- A peak in estrogen causes the LH surge; the presence of LH has negative feedback on estrogen levels and they begin to drop; there is a small FSH surge with the LH surge
- Ovulation occurs when estrogen levels are minimal
- FSH induces follicle development and progesterone levels rise; maximal progesterone in turn has negative feedback on FSH and a decrease in FSH causes a decrease in follicular development and consequently a drop in progesterone

The proximity of fibroblasts, macrophages and mast cells suggests these also participate in paracrine regulation of ovarian activity. Ovarian receptors also regulate cyclic AMP formation, and intracellular calcium levels. Receptors possessing tyrosine kinase act on cellular metabolism. Receptors also serve as ion channels, and enable electrophysical responses.

Oestrus behaviour: Sexually characteristic behaviour of the female at time of ovulation

Relationship to copulation and fertilisation:
Oestrous behaviour allows for better mounting, and hence copulation, by the male. This is demonstrated by the “rigidity reflex” in sows. It is believed to be at least partly induced by pheromones from the boar, but only affects sows in oestrous, and allows better access and mounting dorsally and from the rear by the boar, and thus copulation. The reflex is part of more complex changes in the female which improve fertilisation. The cat requires vaginal stimulation to initiate its ovulation, and thus its receptive and non-receptive cycles leading to multiple copulations with a male vastly improve its ability to obtain fertilisation.
Oestrous behaviour affecting position can also improve chances of fertilisation by increasing the chances of attracting a mate. In solitary animals, oestrous behaviour is what allows the female to be receptive to the male.

Timing of estrous in various animal species





Changes in reproductive tract during the estrous cycle


"

Front 58

"116.          Fetal membranes. Pregnancy recognition. Implantation, fetomaternal unit. Types of placenta. Transport through the placenta. Hormones produced by placenta. "

Back 58

"Fetal Membranes:
• Blastocyst still has its zona pellucida (protection)
• Zona pellucida breaks down 6 – 11 days after fertilization
• The inner cell mass develops into the fetus

• The outer cells – trophoblast – form 2 fetal membranes
• – amnion
• – chorion
Amnion:
• Surrounds the fetus

• Delimits a cavity – amniotic cavity (AC, fetus develops)

• Fluid in the AC – provides buoyancy to the fetus
– protects the fetus against mechanical impact
Chorion:
• Grows rapidly and gradually envelops the amnion and the fetus

• + endometrial cells form the placenta
Allantois:
• formed from the hindgut
• gradually fuses with the chorion ? chorioallantoic membrane
Pregnancy Recognition:
• The 1st communication of embryo with the mother is to signal its existence

• Ruminants – chorion secretes interferon-? (inhibits the formation of oxytocin receptors in the uterine eithelium)

• All domestic species – maintain pregnancy by reducing or preventing formation of PGF2?

• Primates – production of hCG (LH-like effect)




Implantation:
• Primates – blastocyst penetrates the endometrium by means of enzymes secreted from the chorion = implantation

• Domestic animals – fetuses develop inside the uterine cavity, no penetration of the endometrium

• Placenta = tissue that develops in these contact regions
– supplies the fetus with nutrients
– transports excretory products and heat from the fetus to the mother
– blood is not mixed
– endocrine organ („fetomaternal unit“)
Types of Placenta:



Feto-placental unit
- The feto-placental unit is the interfunctionality of the two after fixation of the embryo in the uterus.
- Exchange occurs of maternal and foetal circulations via diffusion and active transport.
- The placenta is formed from the interaction of maternal and foetal tissue, and the placenta provides nutrition and mechanical protection.
- It also acts as the foetal lungs (via the placentomas).
- It is an efficient barrier against the transfer of bacteria and most viruses. In cats, cows, guinea pigs, horses and sheep, the placenta can replace production of sufficient progesterone to maintain the pregnancy.
Transport through Placenta:
In the embryo – allantois functions as a storage reservoir for excretory products

In the fetus – placenta secures adequate transport capacity for nutrients and excretory products between mother and fetus

• Diffusion – water, lipid-soluble substances, O2, CO2, steroid hormones

• Active transport – AA, Ca2+, glucose , water-soluble vitamins

• Larger peptides and proteins are not transported across placenta, accept for Ig during last stage of pregnancy (Hu, ca)
Hormones produced by placenta:
• Transferred to fetal and maternal blood

Functions:

? Stimulation of ovarian hormone production
? Stimulation of fetal growth
? Stimulation of udder development
? Contribution to parturition
1. Gonadotropic hormones:
eCG (equine chorionic gonadotropin)

-- formed in fetal endocrine cells (chorion)
-- transported to the maternal circulation
-- highest level between days 30 – 70 of pregnancy

Functions:
-- stimulates CL to maintain P4
-- stimulates follicular growth, ovulation, and formation of lutein tissue ? ? ovarian secretion of P4
-- when given to animals of other species – acts as FSH
2. Lactogenic Hormones
• CS (chorionic somatomammotropin, placental lactogen)

-- chemically closely related to GH

Functions:

? Stimulates growth of alveoli in mammary tissue during pregnancy
3. Relaxin
• Produced in placenta and ovaries

Functions:

? + P4 – helps to prevent uterine contractions during pregnancy
? Causes connective tissue in the cervix and in ligaments in the pelvis to loosen just before birth

"

Front 59

117.          Hormonal regulation of pregnancy. Species independent and dependent on the corpus luteum during pregnancy. Length of pregnancy.

Back 59

"Hormonal changes during pregnancy:
- Corpus luteum/placental secretion of progesterone is essential for the maintenance of pregnancy
- Relaxin most probably assists in the maintenance of a quiescent uterus, especially in the cat, horse and dog
- Chorionic gonadotropins (CGs) stimulate and extend the activity of the CL during early pregnancy, and in horses, stimulates the ovary to produce oestrogens
- PGF2? is believed to be synthesised in the endometrium, and a massive increase just prior to parturition initiates regression of the CL, and controls the onset of delivery, especially in horses. Other species may rely more on a surge of oxytocin
- Prior to parturition, progesterone levels decrease and estrogen levels increase. The increased estrogen synthesises contractile proteins and gap junctions in the myometrium, to enable sufficient, coordinated contractions
- PGF appearance is preceded by a rise in corticosteroid levels of the foetal plasma

Species Independent on the corpus luteum:
placenta is transformed into a temporal endocrine organ „fetomaternal unit“
– begins to produce gestagens and other hormones

Primates
Horse
Sheep
Cow
Dependant on corpus luteum:
– CL remains the main source for P4 during pregnancy

Dog
Cat
Goat
Swine

"