Bio Midterm 2 Flashcards
Mechanisms of Intercellular Communication (ie between cells)
- Direct communication
- Gap junctions
- Membrane (tunneling) nanotubes
- Mechanosignals
(GMM) - Indirect Communication
- Chemical messengers
Gap junctions
- Connexons and intercalated disks are gap junctions
Connexons: subunits that form a channel (gap function), pore size is very small: permits passage of sugars, amino acids, ions between cells ie metabolic and electric exchange found in ALL CELLS EXCEPT MATURE SKELETAL MUSCLE
- since bones do not connect
Intercalated (cardiac) disks: type of gap junction in cardiac muscle. Allows for rapid and coordinated propagation of action potentials for rhythmic contractions. Smaller than connexons; can be acutely regulated (activated/deativated) by phosphorylation/dephosphorylation
Membrane Nanotubes
Nanotubes are formed in the plasma membrane. They are longer than gap junctions and have a larger pore diameter
- Transfer of nucleic acids, even small organelles, between cells
- Might be a way to transfer cellular componenents from stressed to healthy cells
Mechanosignal Tranduction
Conversion of mechanical stimuli into a cellular response
- Direct physical stress to cells, eliciting a chemical or metabolic response
eg 1: pulsatile and shearing stresses from blood flow on arterial endothelial cells
- Can induce formation of new blood vessels
- If excessive, mediates vascular inflammation and progression of atherosclerosis
eg 2: mechanical stress to muscle fibers from weightlifting resulting in increased protein synthesis
eg 3: remodelling of bone and cartilage through physical stresses (such as weightlifting)
ex 4: conversion of pressure on skin into a neural (electrical) impulse
eg 5: conversion of a sound wave in an electrical signal (hearing)
What are indirect intercellular communication
- Chemical messengers
Autocrine communication is also possible when a messenger acts back on the cell that produced the chemical messenger, but this would probably be considered more of a direct communication
What are the types of indirect intercellular communication?
(a) Paracrine (para close)(acts on a nearby cell): examples of signalling; clotting factors, growth factors eg estrogen (promotes ovary maturation)
- Remember that lots of secreted hormones can act in a paracrine manner and can also act in an endocrine manner
(b) neurostransmitters: synapse is a short distance, neurostransmitter signal must be tightly controlled, not too many molecules released, need an auto shutoff (reuptake or deviation) axons can be long!
(c) hormones: can be water or lipid-soluble, must corss boundaries (membranes), and have target specificity (receptors)
What are the different types of hormones?
Hydrophilic: Water loving: eg insulin, epinephrine, serotonin
- Typically stored in secretory cell
- Dissolved in plasma; no need for carrier!
- Crossing a lipid membrane presents a barrier-so, generally secreted by fusing secretory vesticles to membrane and releasing (exocytosis)
Hydrophobic messenger: Water hating (or lipid-loving)
- Eg steroid and sex hormones (estrogen, testerone, cortisol)
- Storage is typically more limited (ie made on demand)
- Cannot dissolve in plasma; needs a carrier
- Crossing a lipid membrane shouldn’t present a barrier
What is the goal of chemical signal transduction?
To change overall profile of cellular protein/enzymatic activity
What is the process of hydrophobic lipid-soluble chemical messengers
They bind to cystosolic or nuclear receptors (fatty), turns on genes to make new proteins (eg enzymes)
What is the process of hydrophilic lipid-soluble chemical messengers
Binds to cell surface (plasma membrane) receptor, directly, or via second messengers, alters the activity of exisiting enzymes/proteins
Where does amplifiication and signal transduction occur in lipophilic messengers (hydrophobic)
Where does amplification occur?
- Step 3: one hormone/receptor complex can cause many mRNA to be formed
- Step 5: many proteins are formed from each mRNA
Where does signal and hydrophilic messengers take place in hydrophilic messengers
An example with G-proteins
(guanosine nucleotide-binding proteins)
-cAMP is the second messenger
Note the ensuing cascade… activation of one protein (protein kinase A) activates another
- In cytoplasm: A “kinase” phosphorylates a target, and usually uses ATP as the phosphate donor
ONE MESSENGER MOLECULE LEADS TO PHOSPORYLATION OF MILLIONS OF PROTEINS
Signaling systems include?
Can also include, channel-linked receptors (neurostransmitters), and other second messengers (Ca2+, cGMP)
What is phenomenal amplification?
Need to turn a signal off! phospdiesterase breaks down cAMP very rapidly
Process:
- epinephrine (chemical messenger)
- Increase cAMP formation
- Activates Protein kinase A
- Activates hormone sensitive lipase
- Activates liplysis and release of fatty acids to provide fuel during excercise
Chemical classes for lipophobic (water-soluble) and fat-soluble
Water soluble: amino acids, peptides
Lipophilic (fat-soluble): steroids, eicosanoids, thyroid hormones)
Storage in secretory cell
Water soluble: secretory vesicles
Fat-soluble: none
Mechanism of secretion
Water soluble: exocytosis
Fat-soluble: diffusion
Transport in blood
Water soluble: dissolved water soluble
Fat-soluble: bound to carrier protein
Location of receptor
Water soluble: plasma membrane
Fat-soluble: cystosol or nucleus
Signal transduction mechanism
Water soluble: open/close ion channels, activate membrane-bound enzymes G proteins
Fat-soluble: after transcription of mRNA (alter protein synthesis_
Relative time to onset of response
Water soluble: fast
Fat-soluble: slow
Relative duration of response
Water soluble: short
Fat-soluble: long
Relative half-life
Water soluble: short
Fat-soluble: long
Combining neural and endocrine singaling: the neurendocrine (neurocrine) signaling system
Examples:
- Norepinephrine
- Antidiuretic hormone
Secretory cell
Neuron
Messenger
Neurotransmitter (neurohormones)
Pathway
Bloodstream
Target cell
endocrine cells
Specificity
receptors on target endocrine cells
Time to onset
Delayed; duration of effect: longer
Where is norepinephrine released from?
Released from noradrenergic nerves
Where is antidiuretic hormones released from?
From neurons in anterior pituitary
Secretory cell
Nervous sytem: neuron
Endocrine system: endocrine cell
Target cell
Nervous sytem: neuron, muscle, or gland
Endocrine system: most cell types in body
Messenger
Nervous sytem: neurotransmitter
Endocrine system: hormone
Pathway for communication
Nervous system: across synapse
Endocrine system: via bloodstream
Basis of specificity
Nervous system: recpetors on postsynaptic target cell
Endocrine cell: receptors on target cells throughout body
Time to onset of effect
Nervous system: immediate
Endocrine cell: delayed
Duration of effect
Nervous system: brief
Endocrine cell: long
What are the classic endocrine tissues of the body
- Hypothalamus
- Aneterior pituitary
- Adrenal glands
- Pancreas
- Thyroid
- Sex organs (ovaries, testes)
- Kidneys
Most tissues have an endocrine function
What does adipose tissue secrete?
Hunreds of peptides
What regulates fluid secretion into the intestinal lumen
- Matter of chloride and sodium secretion
- Cl- and Na+ pumps are regualted by a protein kinase (and cAMP)
Cholera Toxin and Life Threatening Diarrrhea
- Cholera grows under the mucus layer in the small intestine
- Secreted choler toxin activates G protein for a prolonged period (ie singal doesnt shut off)
- Causes efflux of Cl-, Na+, and water
- Life threatening diarrhea
CFTR Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) a CI- tranpsorter, how is it characterized
CF characterized by a homozygous mutation in the CFTR gene
- Impairs regulation of sweat, digestive juices and mucus (ie thicker secretions, less water loss)
- Could protect the severe loss of fluid that occurs due to the cholera toxin
What is a regulated healthcare professional?
- Physician, registered nurse, nurse practitioner, registered dietation, pharmacist, genetic counsellor, midwife, physical therapist etc
What is public health?
- Public health dietitian, epidemiologist, infectious disease specialist, health communications specialist, environmental health specialist, health policy analyst, biostatistician
What are the components of the control and communication network (CCN)
The central nervous system, endocrine system, peripheral, local support and defense system
Central nervous sytem
Brain and spinal cord
Peripheral nervous system
somatic (directs voluntary movements) and
autonomic (involuntary bodily activities such as heart and breathing rate)
- Parapsympathetic: governs bodily activities during restful conditions
- Sympathetic: prepares body for stressful or emergency situations
Local support and defense system
- Maintenance and support system
- Adaption and repair system
- Resident defense system
- Migrant defense system
5 Major Cell Types of the Adult Human CNS
- Neurons
- Oligodendrocytes (CNS) and Schwann cells (PNS)
- Astrocytes
- Microglia
- Ependymal Cells
What are neurons built for?
Info flow and speed
What is multiple sclerosis?
Destruction of myelin sheath, due to an autoimmune disorder (decreased communication, less myelin, slows nerve signals)
What does myelination help with?
Speed of neurons
What are the nodes of ranvier?
Gaps between myelination
Neurons release how many neurotransmitters?
One type of neurotransmitter at a given pre-synaptic neuron (eg either dopamine, serotonin, norepinephrine, etc)
Can neurons be either inhibitory or excitatory?
Yes, net response is based on an overall (summation) effect of all inputs
- If thereshold is met enough excitatory
Is norephernephrine excitatory or inhibitory?
Excitatory
When do neurons begin?
At around 10 years of age, lots of remodelling of brains neural network
- Developing new synapses
- Pruning away unused ones
In the teenage/emerging adult brain…
- Growth is 90% complete, but there is a massive reorg and development of synapses ie networking
Are teenagers most likely to have dopamine sensitivity?
Yes, more likely to do things that increase risk more dopamine need it
When you are a teen, there is a large increase in…
Myelination, increase in the transmission speed of neurons
What does oligodendrocytes and Schwann cells produce
Myelin
- Oligo span multiple axons and are found in CNS
- Oligo in CNS and Scwann in PNS, Schwann do not span multiple axons
What does astrocytes do?
Stellate (starlike) morphology, very important for communication, more abudant than neurons
What does micoglia do?
Mobile macrophage-like immune cells
What do ependymal cells do? (epidural)
line ventricles to form a barrier; produces cerebrospinal fluid
What are the 5 key functions of astrocytes?
- Coordinate overall function of the blood brain barrier and provide nutrients to feed neurons
- Coordinste function of the ventricle epithelium (brain network)
- Coordinate function at the nodes of Ranvier
- Participate in/form tripartite sysnpases with neurons
- Serve as “super hubs” for neural networks via syncytium formation and calcium signaling (astrocyte clouds)
- Calcium signal propagated from astrocyte to astrocyte by gap junctions
- Astrocyte “cloud” connecting to neuron
What ia the blood brain barrier? (protects what goes in and out)
- Very tight control over what gets through to the brain remember, neurons are meant to be long lived and generally dont regenerate
- Very good protection against most bacteria and toxins
What gets through the BBB?
- Mostly very small lipid soluble compounds (essential fatty acids eg omega 3)
- Also, caffeine and alcohol
- How does glucose get through?… a specific glucose transporter GLUT1 (not insulin sensitive)
- Problem when targetting drugs for the brain
Who was Phineas P Gage
Evidence that different area of the brain are “network” to create our personality
What are emergent properties
personality, rational decision making and processing of emotion
What are pet scanners?
positron emission tomography (glucose tracker)
FMRI?
Functional Magnetic Resonance Imaging (fMRI): tracks blood oxygentated (oxyhemoglobin) vs deoxygnenated (deoxyhemoglobin)
Norepinephine?
- Attention
- Arousal
- Sleep-wake
- Learning
- Memory
- Pain
- Anxiety
- Mood
Psychostimulants:
- Methamphetamine
- Ritalin
- Caffeine
What is an ADHD treatment?
adderall
What are smart drugs?
nootropics
Serotonin network?
- Pain
- Sleep-wake cycle
- Emotion- contributor to feelings of well-being and happiness
How do antidepressants work?
Increasing serontonin levels
What are low serotonin levels?
Associated with migraines
Acetylcholine
- Arousal
- Sleep-wake
- Learning
- Memory
- Sensory Info
What is alzheimers associated with?
Massive loss of cholingic neurons, low acetylcholine levels
Various drugs in Canada available in Canada treat Alzheimers are…
Cholinesterase inhibitors (is the enzyme thst breaks down acetlycholine in the synapse)
Dopamine network modulates?
- Motor control
- Reward/pleasure centres
What are dopamine agonists used for?
Increase healthspan of those for Parkinsons disease
What is dopamine used for?
Addictions
What does cocaine and addictive drugs for?
Blocks dopamine reuptake
What type of neurotransmitter is dopamine
Excitatory neurostrnasmitter (turns signal on)
GABA is….
An inhibitory transmitter (turns it off)
Top foods highest in phenyalanine?
beef, lean chicken, pork, tofu, tuna, pinto beans, milk, squash and pumpkin seeds, pasta, and sweet potatoes
What are the role of hormones?
- Growth and devlopment
- Homestasis
- Reproduction
Where do hormones come from?
- Endocrine glands
- Nerves
- Organs (produce hormones as a secondary function)
- ADIPOSE TISSUE
- SKELETAL MUSCLE
The Nervous System Interacts with the Endocrine System to Form the Foundation of the Control and Communication Network (CCN)
- some nerves release their neurotransmitter directly in the bloodstream (neurohormones)
- all primary endocrine glands and secondary endocrine tissue are innervated by neurons of the automatic nervous sytem
NEUROTRANSMITTERS CAN MODULATE HORMONE SECRETION - neurons in the cns and pns have receptors for many hormones eg insulin, estrogen, tedtosterone
What does norepinephrine mean?
epinephrine (increase), insulin (decrease)
Neurotrasmitters?
messengers released by nerve cells (neurons) that trannsmit signals to adjacent cells, within the nervous system. They act as synapses, the junctions between nerve cells snd their target cells (neurons, muscle cells, or gland cells)
Neurohormones?
neurotransmitters, instead of acting at synpases, are released into the bloodstream, by neurons. Once in the bloodstream, they travel to distant target cells or glands, where they ecert their effects. In this way, neurohormones act more broadly on the body, influencing the function of endocrine glands aznd the release of hormones
What hormones does the posterior pituitary gland release?
Releases oxytocin (OT) and antidiuretic hormone (ADH); anterior pituitary releases many hormones; posteriour pituitary releases neurohormones made in hypothalamus
Is the posterior pituitary an endocrine gland?
No, its more of a collection of nerve endings that release oxytocin and ADH into the pituitary’s circulation
What does OT help with?
uterine contraction, milk ejection, positive mood
What does ADH help with?
Retention of fluid by the kidneys
What does oxytocin help with?
Implicated in social cognition and behaviour (low levels are associated with autism spectrum disorder)
- Depression, anxiety and stress associated with low oxyotcin
What does antidiuretic hormone (aka vasopressin) help with?
- Plays an important role in blood pressure regulation
- Increased ADH release with heart failure (mechanism to support blood presure in response to reduced blood flow) leads to water retention and fluid overload that tends to worsen heart failure symptoms
- Increased ADH release in response to severe blood loss or dehydration (mechanism to try to increase water retention and maintaining blood pressure; hypovelmic shock can be life threatening)
What does anteriour pituitary act like?
Acts like a gland, contains endocrine cells that release many hormones
What are prohibited drugs?
- Anabolic androgenic steroids
- Peptide hormones, growth factors and related substances
- Stimulants
- Naroctics
- Cannabinoids
Why are anabolic steroids harmful?
- effective dose is supraphysioligcal
- dose of the hormone/hormone agonist is generally not timed to mimix natural hormone production
- Remember that hormone are released according to complex ultradian, circadian, and infradian rhymths
Many hormones are erogenic aids?
Yes, and are banned because of it
What is the first line of defense?
External physical barriers
eg tears, skin, large intestine, saliva, repsiratory tract, stomach, bladder
What are second line of defense?
Internal resident cells, proteins, inflammation and fever. It identifies foreign (non-self) matter, but isnt specific and doesnt develop a memory (just gets rid)
What are examples of defensive cells and function?
Phagocytic cells such as neutrophils and macrophages, eosinophils, and natural killer cells; engulf invading organisms, kill parasites, and kill invading organisms and cancer cells
What are examples of desenive proteins and function?
Interferons, coomplement system; slow the spread of viruses in body, stimulates histamine release, promotes phagocytosis, kills bacteria, enhances inflammation
What examples of inflammation?
widening of blood vessles and increased capillary permeability, leading to redness, heat, swelling and pain; brings in defensice cells and speeds healing
Fever?
Abnormally high body temp; slows the growth of bacteria; speeds up body defences
What is cell-based defence in which it is destruction by phagocytosis?
Macrophages: pseudopod about to engulf a bacterium
Natural killer cell attacking a cancer cell
What are phagocytes?
Neutrophils: first on scene, consume bacteria
Macrophages: comsume almost anything
What are non-phagocytes?
Target pathogens/invading organimss are too large for phagocytosis
Eosinophils: discharge enzymes that digest target
Natural killer cells: constantly circulate and patrol for non self. Targey cancer cells. Release preforin and proteases to destroy cells
What are protein based defence?
Lysis by the complement system
- 20+ proteins sythesiezed by the liver are released in an inactive form
- Normally deactivated by native proteins in the blood and the surface of the body’s own cells
- Become activated by i) polysaccharides on bacterias surface, or ii) antigen/antibody complexes (adaptive immune response)
- Enchances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the body, promotes inflammaton and attacks the pathogen’s cell membrane
Inflammation as a defensive process…
Some phagocytes are already on site (resident), some migrate in due to chemical signals
- Inflammation also occurs in reposonse to tissue damage and stress, such as
- Bruises and torn tisues (acute inflammation)
- Disease states, such as arthritis, obesity (chronionc inflammation)
Do you need to have an infection to have a fever?
No, these are classified as the fever of unknown origin. Some potential causes are endocrine disorders, cancer, drug reactions, and potentially others
What are functional cells aka parenchymal cells?
- Functional portion of tissue (gland, organ)
- Usually the most prominent cell type in terms of mass
Examples of parenchymal cells
- Liver-hepatocyte
- Skeleteal muscle- myocyte
- Heart- cardiomyocyte
- Brain- neurons
- Adipose tissue- adiopocytes
- Pancreas- various secretory cells
What are stromal cells aka known as support cells?
- Also called non-parenchymal cells
- Like a framework; supports the parenchymal cells, forming the LSDS
Examples of stromal cells:
- Neurons- control function of virutally all cells/tissue
- Astrocytes- supports neural function, BBB
- Capillary endothelial cells- control blood flow, provide nutrients, oxygen
- Cells of lymphoid origin- resident T-cells/B-cells, NK cells
- Cells of myeloid (bone) origin: neutrophils, macrophages
- Fibroplasts: make extracellular matric and collagen
- Stem cells: divide and replace parenchymal (functional) cells
- Gap junctions: communication between parenchymal cells eg intercalated disks between cardiac cells
What is the stromal view of things?
Support, communication and defense
ie nerves, macrophages, cellular matrix, gap junctions
Does the local support and defense system (LSDS) does more than defend against invading microbes… what does it do?
- LSDS is always functioning
1) local tissue damage by processes that are not due to infectious pathogens
2) Normal tissue turnover: - cell death
- tissue repair, regeneration during wound healing
3) Looks out for appearance of transformed cell populations (cancer)
What is known as the innate immune system?
First and second line of defensice innate: not learned through experience
What is the third line of defense?
Immune response, also known as the adaptive immune system; learned body recognises virus
What are MHC’s?
Major histocompatibility complex markers are proteins expressed on the surface of the cell. They are used in the recognition of pathogens (attack) in immune responses, but also “self” (support)
Does MHC display both self and non-self antigens
Support (to get rid) and attack (see it not itself) labels as self or friend
Steps in recognition…
Step 1: Threat
Step 2: Detection
Step 3: Alert (presents the antigen to a helper T cell and secretes a chemical that activates the helper T cell)
What are steps needed to activate the helper T cell?
Recogntion and verification just to be sure its responding to its non self
- Helper T takes it to next level
What is it in stage 1?
Threat; antigen
What is it in stage 2?
Detection; macrophage
What is it in stage 3?
Alert; helper T cell (after T-cell it divides)
What are the 2 topics in stage 4?
Alarm
B-cell response and T-cell response
What is the T-cell route of attack?
What is step 5? building specific defenses, and splits into memory cytotoxic T cell and Effector cytotoxic T cells find cells displaying foreign antigen, they kill by chemical means eg perforins, which punch holes in the target cell membrane, memory T cells are stored for continued surveillance, cells infected with intracellular pathogen, cancer cells; cells of organ transplants
What is the B-cell route of attack?
Difference B cell has antibodies (right next to A)
What do antibodies do?
Neutralize foreign proteins (toxins), note that antibodies attack the foreign antigens wherever they find them- circulation, tissues, etc. B cells themselves DO NOT engage, antibodies bind to specific antigen (s) that initiate the above event
Remembered in the form of Memory Cells
Memory Helper T Cells, Memory Cytotoxic T Cells, and Memory B cells, memory cells are stored (hopefully for a lifetime) in the bone marrow and thymus
What happens in terms of an autoimmune condition
Attacks healthy cells, specific to T-cells
What are some examples of autoimmune conditions?
Celiac disease
What is negative feedback?
T-supressor cells (also called T regulatory cells, Foxp3+ cells) supress activation of the immune system particularly production of the T helper cells this is important in allowing tolerance to self antigens
What happens when there is too little T supressor?
Autoimmune disease, allergies etc
What are the three systems of the cardiovascular system?
Heart, blood vessels, and blood
What are the affiliated organs/tissues?
- Lymph, cerebrospinal fluid (CSF), extracellular fluid
Examples of cardiovascular (CVD)
- Coronary artery disease
- Stroke
- Heart attack
Where does deoxygentated blood enter?
Returns to right side of heart (enters right atrium) from venous circulation, atria recieve blood, heart contracts, pumps blood to ventricles, right ventricle to the lungs to left atrium
Where does oxygenated blood go?
Leaves left ventricle via the aorta
Deoxygenated blood is in the…
Pulmonary artery
Oxygenated blood is in the…
Pulmanory vein
Arteries
They are thick walls (smooth muscle) designed to handle high pressures
Arterioles
Bit less muscle (pressure is now dropping), but there is loss of innervation to control smooth muscle contractions
Capillaries
No muscle- so, there’s no control over diameter, or connective tissue- no ability to withstand high pressure. But movement of fluid and solutes is maximized here
Venules
Main site of lympocytes (white blood cells) crosssing from blood to lymph notes
Veins
Thin walled, fairly musclar, for easy expansion and recoiling
What does LDL-chloesterol (“bad” cholesterol)
Increased plaque
What does blue blood vessels mean?
Deoxygenated blood
What does red blood vessles mean?
oxygenated blood
High velocity and small surface area
Direct, rapid conductance of blood
The cardiac output is?
Amount of blood pumped by the heart per minute. It is a product of heart rate x storke volume
Blood is moved…
Against gravity
What do valves do?
Prevent blood flowing backwards
What are varicose veins?
- One way valves malfunction
- Allow backwards flow of blood and pooling
What is the name of cardiac muscle tissue?
myocardium
What neural input?
involuntary, autonomic
What is neural conduction?
gap junctions, very fast, contract as a unit
What is metabolism?
very high oxiadative capacity
- LOTS of mitochondria- 35% of volume compared to -5% in skeletal muscle
- Fatigue resistant! Beats- 3 billion times over a lifetime
Diastole… TM
Tricuspid and mitral valve open and close
Systole…PA
Pulmanory and aortic valve (close) open and close
AV valves closing, and semilunar valves closing.
Stenosis
Narrowing of a valve
