Week 3 Flashcards
How can you tell if viewing the inferior or superior view of the calvicle?
The superior view is smooth
Inferior has grooves and tuberacles
The pectoral girdle consists of what bones?
What is its purpose?
Sternum
Clavicle
Scapula
To suspend the upper limbs to the axial skeleton
Name 4 notable anatomic features of the inferior view of the clavicle
1.) Costoclavicular ligament impression
2.) Subclavian groove
3.) Acromioclavicular ligament impression
4.) Conoid tuberacle
Where is the subclavian groove located?
Inferior view of the clavicle in the medial two third portion of the bone
Where is the conoid tuberacle located?
Inferior view of the lateral portion of the clavicle
Where is the costoclavicular ligament impression located?
Inferior view of the medial most portion of the clavicle
What is the term for the flat anterior face of the scapula
Subscapular fossa
State the descending order of the arteries brachiocephalic trunk artery coming off the aorta
1.) Branches into two parts
1a.) R Common carotid
1b.) Subclavian > Axillary > Brachial
When does the subclavian artery become the axillary artery?
After the artery passes beneath the 1st rib
When does the axillary artery become the brachial artery?
After passing underneath pectoralis minor and teres major muscle. At the lateral border of the teres major muscle the axillary artery becomes the brachial artery
The 3rd part of the Axillary artery branches into 3 parts including the: subscapular artery. Name the remaining 2 branches and why they are named as such
1.) Anterior circumflex humeral artery
2.) Posterior circumflex humeral artery
Named as such because of the direction they travel around the surgical neck of the humerus
What muscle indicates the change from axillary artery to brachial artery?
Teres major
Are these veins superficial or deep?
Cephallic vein
Basilic Vein
Medial cubital vein
Superficial
Name the vein that matches this description:
Originates from hand & wrist on radial side. Runs along the lateral aspect of the arm and forearm. Will join the subclavian vein at the axilla
Cephallic vein
Where is the cephallic vein found?
Lateral portion of the arm, from the hand and wrist on the radial side, joins with the subclavian vein at the axillary region
Name the vein matching this description:
Runs along the middle aspect of the arm
Joins the basilic vein at the axillary region to form the axillary vein
Brachial vein
T/F: There is a subclavian vein
True
Name the vein matching this description:
Joins cephalic & basilic vein in the antecubital fossa
Common location for IV access & venipuncture
Medial cubital vein
What 2 veins does the median cubital vein merge together?
Cephalic and basilic vein
What nerve innervates Latissimus Dorsi
Thoracodorsal N
Name the vein that matches this description:
Branched at the distal end, then at the elbow runs medial to form the axillary vein
Brachial vein
What vein does the basilic vein meet at the antecubital fossa?
Medial cubital vein
Where does the axillary vein become the subclavian vein?
Above the 1st rib
From lateral to medial, name 3 veins traveling through the upper arm
Lateral most: Cephalic vein
Middle: Brachial vein
Medial most: Basilic vein
What veins form the “V” type structure at the antecubital fossa?
Lateral most: cephalic vein
Middle forming the inside of the “V”: Median cubital vein
Medial most above the medial cubital fossa: basilic vein
When considering the brachial plexus. which of the ventral rami merge at the roots?
C5 & C6
C8 & T1
How are the cords of the brachial plexus named? Are the cords the medial, middle or lateral most portion of the brachial pelxus
- Named based on their location relative to the axillary artery
- They are the 2nd lateral most portion of the brachial plexus
What anterior rami make up the roots of the brachial plexus?
C5-T1
The pneumonic: “Remember To Drink Cold Beer” is applicable to the brachial plexus. Why?
Sections of the Brachial Plexus from Medial to Lateral most
Roots
Trunks
Division
Cords
Branches
There are 5 roots of the brachial plexus but only 3 trunks, why?
Ventral rami C5 & C6 merge to form Superior Trunk
Ventral Rami C8 & T1 to form Inferior trunk
There are:
____ Roots
____ Trunks
____ Divisions
____ Cords
____ Branches
Of the brachial plexus
5 roots comprised of ventral rami
3 trunks
6 divisions
3 Cords
3 branches
The three trunks of the brachial plexus break off to form 6 divisions, which then merge together to form:
Cords
What divisions of the brachial plexus form the lateral cord?
Anterior division of superior trunk and Anterior division of the middle trunk
What divisions of the brachial plexus form the posterior cord?
All of the posterior divisions of the trunks
What divisions of the brachial plexus form the medial cord?
Anterior inferior trunk ONLY
Which cord of the brachial plexus has only 1 division feeding into it?
Medial Cord
Name the muscle that matches this description:
Inserts on spine of scapula, acromion process, and clavicle
Responsible for rotation, retraction, elevation and depression of scapula
Trapezius
The acronym ________ can help recall the actions of the trapezius. Name them:
Rotation
Retraction
Elevation
Depression
of Scapula
The pneumonic SAC can help you determine the ______________ of the Trapezius. What does SAC stand for?
INSERTION
Spine of scapula
Acromion process
Clavicle
The pneumonic SAC can help you determine the _________________ of the Deltoid. What does SAC stand for?
ORIGIN
Spine of scapula
Acromion process
Clavicle
This muscle inserts on the deltoid tuberosity of the humerus which is on the anterolateral portion of the middle third portion of the humerus
Deltoid
Where does the deltoid muscle insert?
Deltoid tuberosity of the humerus which is located anterolaterally on the middle third portion of the humerus
The pneumonic: Enormous Fat Arms can help recall the actions of the Deltoid. What does this muscle do?
Extension
Flexion
ABduction
What three muscles are located just deep to the trapezius?
Rhomboid major
Rhomboid minor
Levator scapulae
Is Teres major a part of the rotator cuff?
No, while it is in the general region, it does not insert onto the greater tubercle of the humerus/too big to fit within the specific region
What group of muscles inserts onto the greater tubercle of the humerus?
Rotator cuff
Supraspinatous
Infraspinatous
Teres minor
Name the muscle that matches this description:
- Originates in the supraspinatous fossa of the scapula
- Passes beneath the acromion process which makes it susceptible to impingement
- Initiates shoulder abduction
Supraspinatus
What group of muscles originates from the scapula?
Rotator cuff muscles
Supraspinatous
Infraspinatous
Teres minor
Subscapularis
What muscle Originates in the supraspinatous fossa of the scapula?
What is the action of this muscle?
Supraspinatus
Shoulder stabilization
Initiates shoulder abduction
Which teres muscle is involved in shoulder stabilization?
Teres Minor
What muscle within the rotator cuff group matches this action:
External shoulder rotation
Infraspinatus
Teres minor
What two muscles of the rotator cuff share the action of external shoulder rotation
Infraspinatus and teres minor
What muscle of the rotator cuff abducts the shoulder?
Supraspinatous
Which heads of the triceps brachii can you visualize first on dissection?
Long and lateral head
Which is larger on the triceps brachii, the long or lateral head?
Lateral head
What is the action(s) of the triceps brachii?
Shoulder extension & abduction
Elbow extension
Name the muscle that matches this action located in the upper arm:
Shoulder extension and abduction
Extension at elbow joint
Triceps brachii
What is the action of rhomboid minor?
Scapular retraction and rotation
Define anastomoses
A place where 2 arteries come together where blood flows freely
What artery supplies the Trapezius?
Superficial branch of transverse cervical artery
The dorsal scapular artery supplies what muscles (3)
Rhomboids & Levator scapulae
What artery supplies the deltoid? From where does this branch originate?
Posterior circumflex humeral artery which branched from the axillary artery
The suprascapular artery is an artery that forms an anastomoses with the circumflex scapular artery. What 3 muscles does the suprascapular artery supply?
Supraspinatus
Infraspinatus
Teres major
Due to scapular anastomoses, teres major is not only supplied by the suprascapular artery but also:
Circumflex scapular artery
The circumflex scapular artery supplies both teres minor and major, what other artery supplies teres minor
Posterior circumflex humeral artery
What artery supplies the triceps brachii?
Perfunda brachii
Cranial nerve XI innervates the sternocleidomastoid and:
What is another name for cranial nerve XI?
Trapezius
Spinal accessory nerve
What nerve innervates the deltoid?
Axillary nerve
What muscle(s) does the dorsal scapular nerve innervate?
Rhomboids and levator scapulae
The suprascapular nerve innervates what two muscles of the rotator cuff?
What artery supplies these two msucles?
Supraspinatus and Infraspinatus Muscle
Both supplied by Suprascapular Artery
This muscle is innervated by the lower subscapular nerve and supplied by the subscapular artery
Teres Major
What nerve and artery innervate and supply teres major?
Lower subscapular nerve
Circumflex branch of Subscapular artery which runs along the lateral border of the scapula
The superior transverse scapular ligament spans across the suprascapular notch. What artery passes above this ligament and which passes beneath it?
Army Over, Navy Under
Artery over: suprascapular artery
Nerve: Suprascapular Nerve
The axillary nerve and posterior circumflex humeral artery pass through the:
Quadrangular space
The circumflex scapular artery passes through the:
Triangular space on the back
The Radial nerve and profunda brachii pass through the:
Triceps hiatus AKA triangular interval
What nerve and artery pass through the quadrangular space?
Axillary nerve and posterior circumflex humeral artery
What nerve and artery pass through the triangular space?
Trick question, only an artery passes through which is the circumflex scapular artery
What nerve and artery pass through the triangular interval?
Radial nerve & profunda brachii
What borders delineate the quadrangular space of the shoulder?
Teres minor is the top of the triangle
Lateral head of triceps brachii
Long head of triceps brachii
What borders delineate the triangular interval space of the shoulder?
Teres major is the top
Sides are lateral head and long head of triceps brachii
What borders delineate the triangular space of the shoulder?
Teres minor and teres major converge
Long head of triceps brachii
____________ make the extracellular matrix of cartilage. The ECM of cartilage is composed of collagen fibers and proteoglycans. There are additional cartilage-specific forms of glycoproteins (___________) and glycosaminoglycans (______ ______________)
Chondrocytes
Chondronectin
Chondroitin sulfate
Why is it harder for cartilage to grow and repair?
Why might that be a good thing?
There is no vascularization and exchange of nutrients, O2, etc. to allow for regrowth
- This makes cartilage less prone to edema and inflammation
Where might elastic cartilage be found?
Ear & epiglottis
Where might hyaline cartilage be found?
Between joints of long bones, between ribs and sternum
Where might fibrocartilage be found?
Pubic symphysis & cartilage of intervertebral discs
There is a type of cell in the ECM of cartilage, its name matches this description:
island of a few chondrocytes derived from 1 common cell
Isogenous cell groups
In 4 steps, describe the growth stages of cartilage
1.) Tissue dominated by mesenchyme cells, a type of undifferentiated stem cells
2.) Mesenchyme proliferate and differentiate into chondrocytes
3.) Individual chondrocytes produce ECM and the cells become more dispersed
4.) Individual chondrocytes undergo mitosis and form isogenous cell groups
What are the 3 types of cartilage?
Hyaline
Elastic
Fibrocartilage
Is articular cartilage a type of cartilage?
No, it is the location where hyaline cartilage interfaces with bone tissue
Since cartilage is non-vascularized, how does hyaline cartilage receive nutrients?
Synovial fluid joints allow for diffusion of nutrients
Areas of articular cartilage have a slow rate of growth and degradation. What enzymes perform degradation these functions?
Metalloproteinase enzymes in the matrix
What hormones regulate articular cartilage?
Thyroid hormone
Growth stimulating hormone
Inhibited by Adrenal stress hormone
What is special about fibrocartilage?
The chondrocyte groups named isogenic chondrocytes are arranged 90 degrees relative to one another
- Creates tougher texture that increases stability while allowing flexibility and compression
Which part of the intervertebral discs is composed of cartilage?
The Anulus Fibrosis ring is composed of chondrocytes plus ECM
- Nucleus pulposus is ECM only
Describe the orientation of vesicles in pre-synaptic membranes prior to Ca+2 influx
-Some are located very close to the membrane for release into the cleft
- Some are tethered together by actin and are not close to docking location for release into the cleft
Describe 3 actions that result of Ca+2 influx into pre-synapse terminal
1.) Actin filaments depolymerize & dis-associate to release vesicles that are tethered together
2.) Causes vesicles that were previously docked to fuse with the plasma membrane and release NT
3.) Causes more vesicles to dock
Two types of synapses between neurons include chemical and electrical. Describe both
1.) Electrical: synapse is very fast thanks to gap junctions where there is direct passage of current. Found in cardiac muscle
2.) Chemical: neurotransmission across a synaptic cleft. There is a pre- & post- synapse with a cleft in between
What are three options for the fate of neurotransmitters in the synaptic cleft?
1.) Transported by a protein back to the presynaptic membrane for recycling
2.) Inactivation and metabolized by an enzyme on the post-synaptic membrane
3.) An astrocyte can metabolize a neurotransmitter and transport the metabolite or precursor molecule to the presynaptic neuron
Where are sensory (AKA _______-_______________) neurons found?
- Pseudo-unipolar
- Located in a ganglion
Where are motor neurons found?
Anterior horn of the spinal cord
Brainstem
What are local interneurons? What is special about their composition?
They are typically between two neurons in the PNS & CNS
Unmylinated
________________________ neurons are found in the hypothalamus that release peptide hormones in the the blood for systemic or portal circulation
Neuroendocrine
___ axon splits into many _____________________ with one or more _______________. Within each there are multiple synapses/neuromuscular junctions
1 axon splits into many axon terminals with one or more bouton. Within each bouton there are multiple synapses or neuromuscular junctions
The typical direction of action potential along an axon is considered:
Anterograde meaning forward
Opposite to retrograte
A cause of many neurodegenerative diseases is demyelination. This is first indicated by:
Decreased axonal transportation
The adaptive purpose of Nodes of Ranvier is allowing action potential to renew _____________ at each node.
Amplitude
There are many layers of Schwann cells or Oligodendrocytes surrounding the axon. What keeps them tightly wrapped around the axon?
Membrane layers are stabilized by linker proteins
Thus if these proteins are degraded the axon will not be as well wrapped
What are MBP & PMP22?
Peripheral myelin proteins that stabilize the layers of myelin sheath surrounding axons
Describe how Schwann cells act as repair mechanisms for axons after injury.
1.) There is anterograde degeneration along the axon starting at the site of injury.
2.) Macrophages come to promote nerve regeneration & Clean debris
3.) Schwann cells help direct regrowth via providing scaffolding and provide protection for regeneration of axons
Describe how Oligodendrocytes act as repair mechanisms for axons after injury
They don’t! Oligodendrocytes often die and form scar tissue in the CNS
In the PNS: Demyelination along an axon would show a decrease in:
Degeneration of an axon would show decrease in:
Velocity
Amplitude
In the PNS, a reduced velocity of Action potential might indicate:
While a reduction in amplitude of action potential along the axon might indicate:
Demyelination
Axon degeneration
Why are not all peripheral neuropathies caused by demyelinating disorders?
Because sometimes the axon itself is being degeneration which reduces signal aplitude
Slowed electrical conduction of axons in the PNS can cause:
Impaired sensory processing (pain/touch) & muscle weakness
______________ _______________ is an auto-immune attack against the myelin sheath of CNS axons in the brain or spinal cord. Microglia migrate across the blood brain barrier and initiate cell-based attack. This creates focal lesions (injuries), usually 2 ore more lesion sites.
Multiple sclerosis
In _________________ ________ ____________________ (often seen with alcohol abuse), peripheral neuropathy can develop suddenly. It can affect PNS nerves of CNS axons
Vitamin B12 deficiency
What do microglia do?
- Immune surveillance in CNS
- Promoto neuronal homeostasis
- can be potentially harmful if present in excess
What do Astrocytes do?
- Structural role in forming blood brain barrier in CNS
- Maintain normal extracellular environment
- Regulate synaptic function
What do Ependymal cells do?
- Form a single layer along the deepest part of the brain and spinal cord
- Form a blood border between tissue and the cavities (ventricles) that hold CSF
When CNS infection is detected by the body, ________________________ release pro-inflammatory molecules and free radicals (NO & O3) designed to kill microbes
Microglia
After CNS injury, _____________ can migrate to injury cite and phagocytose debris and toxins
Microglia
Astrogliosis is the proliferation of astrocytes. How do these cells respond to tissue damage and inflammation?
The cluster around the area of injury to form a barrier to protect the healthy tissue
Astrocytes not only form barriers for damaged tissue, they also:
Form layer under pia matter and around capillaries in the brain to form the blood brain barrier
Astrocytes are not the only cell type to form a blood brain barrier between tissue and ventricles. What other cell forms a barrier?
Ependymal cells are the inner most layer separating ventricle space from brain tissue
Astrocytes and tight junctions are components that form a barrier for capillaries in the brain from diffusing fluids. What other cell type contributes to this purpose?
Pericytes that envelop endothelial cells to control substances moving across endothelial cells that make up the capillary traveling through
What is white matter comprised of?
Myelinated axons
What is gray matter comprised of?
Cell bodies and dendrites with few to no axons
In the brain, ________ matter is normally superficial to the ________ matter. While in the spinal cord, __________ matter is normally superficial to __________ matter.
Gray matter superficial to white in Brain
White matter superficial to gray matter in spinal cord
Name three overarching components of a peripheral nerve types:
Somatic sensory neuron
Somatic motor neuron
Autonomic unmyelinated neuron
What does the somatosensory system innervate?
Sensation from the skin, muscle & joints
What are ganglia?
Location of cell bodies of neurons
Somatic innervation includes the _______________ and __________________ system.
Skin and muscles
Somatic Sensory innervation includes ________________, __________, _______________
touch, pain and proprioception
Define proprioception
Sensation coming from fascia, skin and bone
Somatic motor innervation includes ________________ muscle.
Skeletal muscle
Afferent nerves:
Supply input to the CNS
Efferent nerves:
Output from CNS to the body
Somatic afferent nerves provide somatosensation. What is somatosensation?
touch, proprioception, pain and temperature
Reflexes not only have automatic responses to stimuli, but also:
Coordination of opposing muscles
Regarding the somatic nervous system, where do sensory neurons synapse?
Sensory neurons go into the spinal cord, bypass their dorsal root ganglion and synapse in the dorsal horn of the spinal cord
Regarding the somatic nervous system, where do motor roots originate in the spinal cord?
Ventral root
In the spinal cord, the anterior horn cells have ___________ cell body with a large __________________ arbor which is corresponding to receiving inputs from many neuronal systems.
Multipolar
Dendritic arbor
Which is larger the dorsal horn or the anterior horn of the spinal cord?
Anterior horn is normally larger
Spinal roots coming off of the spine can:
Veer off into dorsal and ventral rami
Somatic NS: Upper motor neuron cell bodies have axon projections that descend through the brain, and descend to some target level of the spinal cord. What happens after
- The upper motor neurons form a synapse on a lower motor neuron
- The lower motor neurons project to muscle
Glutamate is:
GABA is:
Excitatory
Inhibitory
Describe crossed reciprocal inhibition reflex:
Ex. Action to flex Right hip and knee
An upper motor neuron activates the target muscle.
At the same, activates interneurons that inhibit left lower motor neurons for L hip and knee flexion
Activation of interneurons that activate contralateral antagonists (hip and knee extensors)
Name 6 cutaneous somatosensory nerve endings
1.) Free nerve endings
2.) Hairs
3.) Merkel’s touch domes
4.) Pacinian corpuscles
5.) Meissner’s
6.) Ruffini
What cutaneous somatosensory nerve endings detect Fine/Discriminative touch?
Hairs
Merkel’s touch domes
What do Merkel’s touch domes do?
Detect light pressure, edges, texture
What do hairs detect?
Motion
What do Pacinian corpuscles do?
Detect vibration
What types of cells detect crude touch?
Meissner’s
What do Meissner’s cells do?
Detect crude touch, more specifically, tap, flutter, texture
What cells detect skin stretch and joint movement?
Ruffini cells
What cutaneous somatosensory nerve endings are responsible for detecting proprioception?
Ruffini cells
What do Ruffini cells do?
Skin stretch and joint movement
Somatosensory neurons include proprioception to detect skin stretch and joint movement. What do muscle spindles detect?
What do golgi tendon organs detect?
Muscle spindle: Senses stretch
Golgi tendon organs: senses contraction of muscles
Fine touch somatosensory neurons project straight to the brain, bypassing the spinal cord and DRG.
What is different about temperature and nociception neurons?
They synapse in the spinal cord and then travel to the brain
Cutaneous nerves initially travel between skin & muscle then:
Dive deeper to join major nerves to reach the spinal cord
If there is loss of sensation at a particular dermatome what can this indicate?
Problem at spinal cord or root
Single disc herniation and ____________ __________/_____ can lead to loss of sensation in a single dermatome. This can induce:
Pinched root/nerve
Spontaneous pain or paresthesias in a dermatomal pattern
Lowered amplitude in nerve conduction studies is corresponding to:
Fewer axons/axon degeneration
Decreased velocity in nerve conduction studies is corresponding to:
Loss of myelination in the PNS
Describe how referred pain works
1.) Visceral sensation is received in the spinal cord and synapses with somatic sensory neurons
2.) Cross talk causes: visceral pain perceived as somatic pain in the dermatome of the same spinal cord level
What dermatome might indicate the heart is damaged?
T1-T4, mainly left
What dermatome might indicate there is kidney/ureter damage?
L1-L2
What dermatome might indicate there is damage to the appendix?
T10
What dermatome might indicate there is gallbladder damage?
T7-T8
Stretch reflexes are also known as ____________ ______________ _______________
Deep tendon reflexes
Are reflexes, such as the patellar reflex, mediated by golgi tendon organs or muscle spindles?
Muscle spindles
Describe the patellar reflex:
1.) Tap on patellar tendon creates mild stretch in quadricep muscles
2.) Stretch detected by sensory neuron fibers wrapped around muscle fibers
3.) Sensory neuron fires, releases excitatory NT on motor neuron that activates contraction of quadriceps muscles
Reflex can be activated by passive stretch by an examiner, which activates:
Muscle spindle
Name the three components of a stretch reflex circuitry
Muscle spindle
Sensory arc
Motor arc
What is the purpose of intrafusal muscle fibers of muscle spindles?
Ensures the muscle spindle contracts in unison with the muscle it is inserted within
Globular proteins are often:
Water-soluble
What is the difference in composition of myoglobin and hemoglobin?>
Myoglobin: single polypeptide
Hemoglobin: Tetramer
______ is a prosthetic group containing protoporphyrin IX and a central ferrous iron atom
Heme
What is the charge on a free Ferrous ion vs a bound ferrous iron in the body?
Ferrous free: +3
Ferrous bound: +2
The subscapularis nerve innervates the subscapular and Teres Minor muscle. What actions do they perform?
Medial rotation of the shoulder and abduction
Teres Major and Subscapularis muscle action are medial shoulder rotation and abduction. What nerve innervates these two?
Lower subscapular N
What nerve innervates the deltoids and Teres minor?
Axillary N
The Axillary nerve innervates the:
Deltoids and Teres Minor
A midshaft humeral fracture can result in injury to what nerve and artery?
Radial Nerve
Deep Brachial Arteryy
A fall on an outstretch hand and partially flexed elbow can result in injury to what nerve and artery?
Median nerve
Brachial artery
A fracture of the surgical neck of the humerus can injure what artery and nerve?
Axillary nerve and posterior circumflex humeral artery
What are three main contents of the cubital fossa?
Biceps brachii tendon, brachial artery, and median nerve
Describe the anular ligament of the radius
Encricles the head of the radius to prevent dislocation. Spans from anterior side of the ulnar wrapping around the radius and then attached on the posterior surface of the ulna
T/F: Since fibrous proteins include collagen which is what hair is comprised of, fibrous proteins are normally highly soluble in water
False, they have low water solubility
Collagen, Elastin and Keratin are all types of ______________ ___________
Fibrous proteins
Name three different types of fibrous proteins
1.) Collagen
2.) Elastin
3.) Keratin
______________ is a fibrous protein. Its structure is often Helix. ____________ is a right-handed triple helix of alpha chains
Collagen
Tropocollagen
The alpha chains in the triple helix of tropocollagen consist of Glycine and __________ - ___________ repeats.
Proline
Hydroxyproline/Hydroxylysine
What type of bonds hold together collagen alpha triple helix proteins
Hydrogen bonds form between chairs
There are 5 different types of collagen. Type I is found:
Composed of:
Skin, bone, tendons, cornea
Alpha 1, Alpha 2
There are 5 different kinds of collagen
Type III can be found:
Is composed of
Blood vessels, dermis, lymph nodes, early phases of wound repair
Alpha 1
There are 5 different types of collagen. Type IV is found:
Composed of:
Basement membranes
Alpha 1 - Alpha 6
List the first 4 basic steps of collagen synthesis
1.) Start in the RER of the cell with Hydroxylation
2.) Next glycosylation
3.) The procollagen is secreted out of the RER as a triple helix
4.) Stabilized outside of the ER using cross linking
Regarding formation of collagen, what is being added to the alpha chains during glycosylation?
Glucose and galactose is being added to hydroxylysines
Describe the final step of collagen synthesis that occurs OUTSIDE of the RER
Tropocollagen molecules associate spontaneously to form collagen fibrils. Cross-linking occurs between tropocollagen molecules
What enzyme is responsible for cross-linking during collagen synthesis? With a very basic description, describe cross-linking.
Lysyl oxidase
Links between alpha-helices are formed for tensile strength to form a fiber
What relevance does Vit C deficiency have to collagen?
The hydroxylation or Proline and Lysine in the RER requires Vitamin C for enzymes to function properly, without it Hydroxylation cannot occur
Hydroxylation of Proline in collagen synthesis is important for:
Interchain H-bond formation and formation of a stable triple helix
Hydroxylation of Lysine during collagen synthesis is important for:
Glycosylation of collagen
Cross-linking
The physical findings of: bruises on the limbs, petechiae, gum disease, loosening of teeth. Malaise, lethargy, and myalgia can/are indicative of:
Scurvy
Poor diet, ____________, smoking, and _________ are all risk factors for vitamin C deficiency, known as scurvy
Dialysis
Alcoholism
What two cofactors are required for cross-linking during collagen synthesis?
Copper
Vitamin B6 AKA PLP
Decreased elasticity of skin and joints can be attributed to changes in collagen synthesis. Why?
With increased age, the number of cross-links increases which causes stiffening, decreased elasticity of skin and joints
Cross-linking during collagen synthesis is catalyzed by ___________ __________. Its predominant feature includes ___________ _______________.
Lysyl oxidase
Oxidative deamination
Type I collagen disorders include:
Osteogenesis imperfecta
Ehlers-Danlos syndrome
Type III and Type IV collagen disorders include:
Ehlers-Danlos syndrome
Type I collagen tissues include: skin, bone, tendons and ___________
Cornea
Clinical presentation of osteogenesis imperfecta include: brittle bones, retarded wound healing, _________ ___________, and ____________ ________. It is caused by mutations in either alpha ___ or alpha _____ chain of Type I collagen misfolding.
Hearing loss
Blue sclera
Alpha 1 or Alpha 2
Why might a patient with osteogenesis imperfect present with blue sclera?
The type 1 collagen fibers are not formed correctly in the sclera. This may allow choroidal veins to show through
Ehlers-Danlos can present as hyperextension and hyperelasticity of skin, joints, vessels and colon. What mutations cause this syndrome?
Mutations in Alpha 1 or Alpha 2 chair of Type I, II, or V collagen
In Ehlers-Danlos syndrome, there is a deficiency of lysyl hydroxylase. This would disrupt what step of collagen synthesis?
Hydroxylation of proline and lysine residues in the RER
Alport’s syndrome is a collagen disorder caused by:
Mutation of Alpha 3, Alpha 4, or A5 chain type IV collagen
Alport’s syndrome is a collagen disorder caused by mutations of Alpha 3, Alpha 4 or Alpha 5 collagen type IV. Clinical presentation may include:
1.)
2.)
3.)
1.) Glomerulonephritis
2.) Ocular defects
3.) Hearing loss
Goodpasture’s syndrome, a collagen disorder, is caused by:
Antibodies against the Alpha 3 chain of type IV collagen
_____________ ____________ is caused by antibodies against the Alpha 3 chain of Type IV collagen which destroy the basement membrane of the pulmonary and glomerular capillaries
Goodpasture’s syndrome
Menkes disease is a collagen related disorder associated with depigmented hair, arterial tortuosity and rupture, cerebral degeneration, anemia and osteoporosis.
1.) What kind of inheritance pattern is this genetic disorder?
2.) What cellular problem causes this disorder?
1.) X linked recessive
2.) Deficient cross-linking secondary to functional copper deficiency
Deficient cross linking by the catalyst lysyl oxidase, secondary to functional copper deficiency can cause ________ ___________. A disorder characterized by depigmented hair, arterial tortuosity and rupture, cerebral degeneration, anemia, and osteoporosis.
Menkes disease
Elastin proteins contain:
1.)
2.) very little hyroxylated proline or lysine which means:
2.) similar to collagen in regard to:
1.) small non-polar amino acids
2.) No alpha helix
3.) Cross-linking among tropoelastin
The fibrous proteins collagen are _____________ while in contrast, elastin is ______________
Hydrophobic
Hydrophilic
During the synthesis of elastin, outside of the nucleus, Tropoelastin will combine with the microfibrillar protein that includes ___________-__. Mutliple tropoelastin molecules undergo:
Fibrillin-1
Crosslinking to form the protein elastin
Cross-linking in Elastin differs from collagen in that:
Elastin has a 3-D network of cross-linked peptides that can be linked together to form a clover like shape
Cross linking of Elastin involves cross links Lysine and Allysine being formed by _______ __________. 4 Lysine residues can be cross linked into a ____________.
Lysyl oxidase
Desmosine
What feature of elastin contributes to its elastic properties?
Desmosines
In the lungs, alveolar elastin is constantly exposed to neutrophil elastase. What prevents the elastin from losing its elasticity?
A1-AT aka A1AT
What is A1AT aka Alpha 1 AT? Where is it produced?
It is a protease inhibitor in the alveoli that prevents the alveolar elastin from being degraded
Formed in the liver
_______________ can be caused by mutation of PiZ allele which causes a defiency of A1AT protein. What are the physiologic repercussions?
Emphysema
The tissue is degraded due to constant exposure to neutrophil elastase that destroys elastic properties
Marfan’s syndrome is a disorder of elastin. Describe the cellular deficiencies
There is mutation of Fibrilin-1
What does Fibrilin-1 do for elastic fibers? What disorder can it cause if there are mutations of this glycoprotein?
1.) Component essential for proper formation of ECM including biogenesis and maintenance of elastic fibers
2.) Marfan’s syndrome
This fibrous protein, ___-____________, are tough fibers that are the makers of epithelial cells
Alpha Keratins
Alpha keratins are rich in ________. It does not stretch and is _____________ similar to collagen.
Cystine
Hydrophobic
Contrasted to triple alpha helix of collagen, what is the composition of Keratin helices?
Two pairs of alpha helices to form tetramers
Protofilaments (tetramers of ___-_________) bundles together make up:
Alpha Keratin
Intermediate filaments
______________ ____________ simplex is a disorder of genes encoding Keratin 5 or Keratin 14. Clinical presentation is:
- Epidermolysis bullosa simplex
- Blister formation of EBX occurs at the dermoepidermal junction
______________ ____________ simplex is a disorder of genes encoding Keratin 5 or Keratin 14. Clinical presentation is:
- Epidermolysis bullosa simplex
- Blister formation of EBX occurs at the dermoepidermal junction
What is the most abundant amino acid in collagen?
Glycine & Proline
Collagen is the major protein found in the matrix of cartilage. It is mainly secreted by___________________ and, to a lesser degree, by chondrocytes.
chondroblasts
_____________ secrete collagen in various tissues, including skin, blood vessels, tendons and bones
Fibroblasts
Cross linking of Collagen occurs _________ _________ __________ and is catalyzed by _________ ___________.
Outside of cell
Lysyl oxidase
Which type of collagen forms networks?
Type IV
There are 4 layers of Fascia. Name them:
Pannicular
Axial & Appendicular
Meningeal
Visceral
Provide 2 descriptors of Pannicular Fascia
- Loose and dense irregular connective tissue
- Variable fat content
Where is Axial and Appendicular Fascia found? What direction do the fibers tend to go?
- Surrounds muscles and tors0
- Fibers tend to run in the direction of muscle fibers
Where might meningeal fascia be found?
Dura and other membranes surrounding the CNS
Name the three classifications of fascia
Superficial
Deep
Subserous
Describe subserous fascia and give an example of where it might be found
Loose, elastic tissue
Peritoneum and visceral pleura
Which classification of fascia is subject to collecting inflammatory cells?
Subserous
What is enthesis?
Junction between tendon and the bone where the collagenous fibers of the tendon fuse wit the periosteum of the bone
What are the 7 P’s of compartment syndrome?
1.) Pallor
2.) Pressure
3.) Pain
4.) Piokilothermic (cold)
5.) Paresthesia
6.) Paralysis
7.) Pulseless
What is the difference between elasticity and plasticity of fascia?
Elasticity is RECOVERABLE deformation
Plasticity is NONrecoverable deformation
What is creep referring to regarding properties of Fascia?
Deformation of a viscoelastic material under constant load over time
Compare Hook’s Law vs Wolff’s Law in relation to properties of fascia
- Hooks law: Applied stretch or compression to a tissue results in a proportional change in length
- Wolff’s Law: Function of a bone is followed by changes in internal architecture and external conformation
Release of fascial restriction can ease restrictions to ______________ and biologic function of the enclosed structures and communication with other tissues
Motion
Is this indirect or direct fascial release?
The fascial layers are engaged by compression, twist or traction directly into the restrictive barrier. Force is maintained until release is felt
Direct fascial release
In what direction is force applied in direct fascial release?
Force is exerted perpendicular or parallel to fascial fibers
Is this direct or indirect fascial release?
Utilizes the point of ease during passive range of motion, where elastic forces are in balance.
Indirect fascial release
Globular proteins are spherical in shape and:
H2O Soluble
Compare the structure of Myoglobin vs Hemoglobin
Myoglobin is tertiary structure
Hemoglobin is Quaternary structure
When observing the structure of Heme, there are alternating groups of P & M. What are the groups composed of?
P: propionate group, Carbon chain with carboxyl group at the end
M: Methyl group
When observing the structure of Heme, there are alternating groups of P & M. What are the groups composed of?
P: propionate group, Carbon chain with carboxyl group at the end
M: Methyl group
In heme there are rings, A-D. Which ring has special conformation?
D
Where does Oxygen bind on the heme molecule?
Oxygen binds to the Iron molecule
What is the charge of free iron AKA ferrous ion?
Fe +2
What is the charge of the bound iron aka Ferric ion
Fe +3
What are the two forms of Hemoglobin?
T form and R form
Describe the oxygenation state of T form of Hb
Low oxygen affinity state because heme is in a slightly bent structure which makes it difficult for Oxygen to bind
After binding to the iron, oxygen:
Temporarily and reversibly oxidizes Fe+2 to Fe+3 while oxygen temporarily turns into superoxide
After binding to the iron, oxygen:
Temporarily and reversibly oxidizes Fe+2 to Fe+3 while oxygen temporarily turns into superoxide
Describe the R form of heme
Molecule is in the relaxed state with high Oxygen affinity
Why does myoglobin exhibit a hyperbolic disassociation curve while Hemoglobin exhibits a sigmoidal disassociation curve?
Hemoglobin has cooperativity
What molecule will bind to Myoglobin in place of O2 and form a much tighter bond?
CO
List 5 factors that alter Oxygen affinity of hemoglobin
1.) Temperature
2.) pCO2
3.) 2,3-BPG
4.) pH
5.) pO2
Regarding globular proteins: What are allosteric effects for O2 binding?
Factors that alter the oxygen affinity of hemoglobin
The Bohr effect is describing the effect of _____ on Hemoglobin dissociation curve
pH
Overall, a DECREASE in Oxygen affinity for hemoglobin would result in what type of shift on the dissociation curve?
Shift to the RIGHT
Overall, a DECREASE in Oxygen affinity for hemoglobin would result in what type of shift on the dissociation curve?
Shift to the RIGHT
Overall, an INCREASED affinity to Oxygen would reflect what kind of change on the Hemoglobin dissociation curve?
Shift LEFT
Overall, an INCREASED affinity to Oxygen would reflect what kind of change on the Hemoglobin dissociation curve?
Shift LEFT
A ____________________ in pH would reflect a more acidic environment, which would decrease Oxygen affinity for Hemoglobin which would reflect what type of shift for the Hemoglobin dissociation curve?
Decrease in pH
Shift Right
At a lower pH, a _________________ partial pressure of Oxygen is required to achieve any given oxygen saturation
Greater
Thus at lower pH more Oxygenated environment is required to achieve normal saturation
An increase in 2,3 BPG would reflect what kind of curve shift on Hemoglobin-Oxygen dissociation curve?
Increase 2,3 BPG would shift curve Right indicating LOWER oxygen affinity
What is 2,3 BPG?
A byproduct of Glycolysis
The binding of CO2 stabilizes the T form of Heme which would indicate what type of curve shift on Hb-Oxygen dissociation curve? Why?
Right shift
The T form of Heme is the bent structure that does not bind easily to Oxygen, thus if we stabilize it, Heme will be further lowered affinity for Oxygen binding
The fetal form of Hemoglobin has high or low affinity to 2,3 BPG? Using this information, what can you deduce about its Oxygen affinity?
HbF has low affinity for 2,3-BPG thus has Higher Oxygen affinity compared to HbA
What is the composition of HbA?
α2 β 2
What is the composition of HbA?
α2 β 2
What is the composition of HbF?
α2 γ2
What form of hemoglobin is predominant in normal human conditions?
HbA
What form of hemoglobin is predominant in normal human conditions?
HbA
What is the composition of HbA2?
α2 δ2
What is the composition of HbA1C?
α2β2-Glucose
_________________ are a group of inherited hematologic disorders caused by defects in the synthesis of one ore more of the hemoglobin chains
Thalassemias
_____ thalassemia is caused by reduced or absent synthesis of α globin chains. While ___ thalassemia is caused by reduced or absent β globin chains
α Thalassemia
β Thalassemia
_____ thalassemia is caused by reduced or absent synthesis of α globin chains. While ___ thalassemia is caused by reduced or absent β globin chains
α Thalassemia
β Thalassemia
In ____ thalassemia, HbA2 levels would be increased to compensate for the decreased level of _______ form.
β-thalassemia
HbA
What are the predominant types of globin chains in hemoglobins?
β and alpha, particularly alpha
Where does transcription of Hemoglobin occur? Where does translation of Hb occur?
Nucleus
Cytosol
At alkaline pH, which Hb type travels toward the anode the fastest? Why?
HbA
HbS is a change of Glutamic acid for:
Valine
HbC is a change of Glutamic acid for:
Lysine
1.) Both HbS and HbC exhibit similar presentation of RBC:
2.) How can they be differentiated?
1.) Sickling, HbS > HbC
2.) Can tell by determining which amino acid was inserted instead of Glutamic Acid
HbS: Val
HbC: Lys
What happens Glu is exchanged for Val at position 6 of the Beta chains in HbS disorder?
HbS polymerizes to form fiber thus cells are rigid and misshapen = sickling and decreases RBC
1.) Which form of hemoglobin disorder is worse? HbS or HbC?
2.) Why?
HbS > Hbc
2.) HbC is unstable and does not polymerize as significantly as HbS and thus fewer cells are sickled
Which is more negatively charged HbS or HbA? Why?
HbS has no glutamic acid to make it - charged since the Glu was substituted for Val
At neutral pH what charge does Lys have?
+1
At pH 7.4, the only negatively charged side chains are the carboxylates of:
glutamic acid and aspartic acid
At alkaline pH what charge does Valine have?
Negative
What is the charge of Lys at pH 8?
+1
What is the basic function of ferritin?
Store Fe+3
________________________________ transports Fe+3 in the blood and liver
Transferrin
What is the action of Transferrin?
Transports Fe+3 ions in the blood and liver
What is the charge of Fe+2 in the cytosol of a cell?
Fe+2
What do transferrin receptors do?
On the surface of cells to bring F+3 inside the cell
Duodenal Cytochrome B or Dcytb protein changes Fe+3 (______________________) to Fe+2 (____________________)?
Ferric iron
Ferrous iron
_______________________ receptors reside on the surface of cells to bring in Fe+3 into the cytosol of a duodenal enterocyte
Transferrin
_______________________ or Dcytb protein changes Fe+3 to Fe+2 in duodenal enterocytes?
Dudodenal cytochrome b
Duodenal Cytochrome B or Dcytb protein changes ____________ ___________ to _________________ in duodenal enterocytes
Ferric iron to Ferrous iron
What is Hepcidin?
A hormone which inhibits Ferroportin
What does Divalent metal ion transporter-1 do?
Imports Fe+2 into many cell types
What does STEAP-3 protein do?
Converts Fe+3 to Fe+2 in **blood cells*
_____________________ acts in the liver and intestine to export Fe+2 from inside the cell into bloodstream on the basal surface.
Ferroportin
What does Ferroportin do?
Acts in the liver and intestine to export Fe+2 from inside the cell into the bloodstream on the basal surface of the cells
Decreased hepcidin hormone would allow ferroportin to continuously act which would:
Increase Fe+2 being allowed into the bloodstream = iron overload
Increased hepcidin hormone would disallow action of ferroportin which in turn:
Decrease the amount of Fe+2 being allowed into the blood stream = decreased iron levels
Is Ferroportin on the basal or luminal side of enterocytes?
On the basal side that contacts with the interstitium and bloodstream
What converts Ferrous iron to Ferric iron on the basal side of duodenal cells for transport into the bloodstream?
Hephaestin
What is the action of Hephaestin?
Converts Ferrous iron to Ferric iron on the basal side of duodenal cells for transport into the bloodstream.
____________________ converts Fe+2 to Fe+3 on the basal side of duodenal cells for transport into the bloodstream.
Hephaestin
What receptor might be have increased expression when iron levels are low? Why?
Transferrin receptor (TfR1)
Because increasing the receptor that brings Fe+2 into the cell would increase iron levels
What is TfR1?
Transferrin receptor
T/F: Transferrin receptor intakes Transferrin/Fe+2 complex and Fe+2
False, Fe+2 is imported via DMT1 receptor
In most cells, what are the 2 general receptors that transport iron into the cell?
DMT-1 & Transferrin Receptor
Prior to taking in Fe+2 into the cell via DMT-1, what protein converts Fe+3 to Fe+2 in general cell types?
STEAP 2
Which protein receptor does NOT need to convert Fe+3 to Fe+2 prior to moving iron into the cell?
Transferrin receptor/Transferrin/Fe+3 complex
After Transferrin receptor brings in Fe+3 into the cell cytosol what happens next?
1.) Vesicles existing in the cell have STEAP-2 proteins that endocytose Fe+3 to convert to Fe+2
2.) Fe+2 is pumped back into the cell cytosol via DMT-1
When iron levels are high, what can you deduce about the level of Ferritin expression and Transferrin/Transferrin Receptors?
Ferritin expression HIGH to store Fe+3
Transferrin & Transferrin Receptor level LOW to prevent Hemochromatosis
What is hemochromatosis?
Iron overload
In iron deficiency anemia, what can you deduce about the levels of Ferritin and Transferrin/Transferrin Receptor?
Ferritin levels LOW, because there is little iron to store
Transferrin levels HIGH to try and bring in as much iron as possible
