Module 1 Flashcards
Antiport
Na - K Movement of two different ions in opposite directions
Symport
sodium and glucose Carries two different ions in the same direction
Uniport
Lone glucose Carries one ion
Hyperpolarization
Movement further away from zero during after an action potential (overcorrection to a negative state). Protects the cell from stimulation during repolarization.
Gap Junctions
Form direct cytoplasmic junctions between cells
Contact Dependent Signals
e.g neurotransmitters and synapses
Contact Dependent Signals
e.g neurotransmitters and synapses
Autocrine Signals
Act on the cell that secreted them
Paracrine Signals
Secreted by one cells and diffuse to adjacent cells
Mendelson’s First Law
The Law of Segregation: Each gamete carries only one allele for each gene (egg has one, sperm has one)
Mendelson’s Second Law
Law of Independent Assortment: Genes for different alleles can segregate independently when gametes come together
Epistasis
A gene at one locus alters the expression of another gene at a second locus
Penetrance
The degree of display of a gene
Carcinoma
Ca arising from epithelial tissues
Adenocarcinomas
Arise from ductal or glandular tissues
(breast duct CA = mammary adenocarcinoma)
Sarcomas
Ca arisinf rom mesenchymal tissues (connective tissues, skeletal mm, bone)
Lymphomas
Ca arising from lymph cells
Leukemias
Blood Cancers
Carcinoma In Situ
preinvasive tumors (“In place”)
glandular or squamous cell origin
Neoplasm
Abnormal growth following uncontrolled cellular proliferation but NOT necessarily cancer
Cancer
disease in whcih abnormal cells dicide without control and are able to invade other tissues
Anaplasia
Hallmark of Ca
Loos of differenctiation
Pleomorphic
Hallmark of CA
cell with marked variability of size and shape
The hallmarks of Cancer
Sustaining proliferative signaling
Avoiding immune destruction
evading growth suppressors
enabling replicative immortality
tumor promoting inflammation
activating invasion and metastasis
genomic instability
inducing agiongenesis
resisting cell death
deregulating cellular energetics
driver mutations
drive the progression of cancer. A critical number of these drivers are required in order for a cell to become cancerous
passenger mutations
random events that do not contribute to malignancy
Stroma
The tumor microenvironment that surrounds and infiltrates the tumor
What are Receptor Tyrosine Kinases?
cell membrane receptors that initiate proliferation
mutations causing lung cancer are associated with activation of RTKs
Autocrine Stimulation
Ability of a cancer to create its own growth hormone
RAS
Protein on the membrane which is normally inactivated, but once activated in turns activates multiple signalling pathways that guide the cell into proliferation.
A point mutation in RAS converts it from an unregulated proto-oncogen to an unregulated oncogene
What kind of mutation is Burkitt Lymphoma an example of?
Example of a translocation which causes inappropriate production of a proliferative factor (in this case it produces a factor that leads to proliferation of B lymphocytes)
What mutation causes Chronic Myeloid Leukemia?
Example of a translocation leading to novel protein production with growth promoting properties
What is Translocation?
when a piece of one chromosome is swapped with a piece from another chromosome.
What are Tumor supressor genes
Anti-oncogenes
Retinoblastoma gene is an example of what kind of mutation?
Example of tumor supressor gene mutation
What is TP 53?
p53 Tumor supressor
“Guardian of the genome”
monitors cell stress and activates caretaker genes
What is unique about Tumor Suppressor Gene Inactivations?
REQUIRES TWO INACTIVATIONS BECAUSE A COPY IS RECEIVED FROM EACH PARENT
What is Genomic Instability?
When caretaker genes are mutated or silenced, more mutations occur and accumulate
Oncomirs
miRNA that stimulate cancer development by regulating pathways controlling stability
What are BRCA 1 and 2?
TSGs and caretaker genes that repair double stranded DNA breaks
Angiogenesis
Production of vasculature to support a tumor
What is HIF-1a?
regulator of angiogenesis in normal tissue
What is TSP-1?
Angiogenesis inhibitor
What are MMPs?
What do they do?
Matrix Metaloproteinases
Break down ECM to release/activate stored angiogenesis factors
What does OXPHOS stand for?
mitochondrial oxidative phosphorulation AKA normal cellular aerobic respiration
Warburg Effect
When cancer cells reprogram to glycolysis instead of OXPHOS
AKA “Aerobic glycolysis”
Beneficial shift that creates more products of glycolysis which are then used for more efficient production of proteins etc
reverse Walburg Effect
when cancer cells use OXPHOS but manipulate the cancer associated fibroblasts to undergo aerobic glycolysis, increasing byproduct availability for production
How is GLUT1 used by cancers?
upregulated by oncogenes etc to increase tranpsort of glucose into the cytoplasm
What is the Mitochondrial Pathway for Apoptosis
In normal cells, when DNA damage is irreparable T53 is activated and induces transcriprtion of pro-apoptotic factors which lead to cell death
What is the “Death Receptor”
Fas, Fas associated death domain (FADD)
When activated on the cell membrane, triggers internal apoptosis via caspases
What is the role of TAM in protecting cancer?
Tumor Associated Macrophage
Tumor cells secrete factors (CCL2, CSF1, MCP1) that draw immature monocytes into the tumor, and alter their development into TAMs that mimic M2 versions of macrophages (which produce anti-inflammatory mediators)
This protects the tumor from the immune systems
What is a CAF? What does it do?
Cancer associated fibroblasts
synthesize the extracellular matrix surounding and permeating the tumor
Growth factors, MMPs etc secreted by them to aid the cell
Tumor Associated Antigens
Products of oncogenes, antigens from oncogenic viruses oncofetal antigens etc
Should attract T lymphocyte and NK cells to attack
Most malignancies are suppressed by efficient immune response against these tumor antigens
What are TILS?
Tumor infiltrating lymphocytes
Treg cells that ordinarily promote wound healing by limiting autoimmune reastions
Tumors actively recruit these and alter them to precent destructive antitumore immune responses
Epithelial-mesenchymal Transition (EMT)
Transition to metastasis
Anoikis
When normal cells are separated from their extracellular matrix, they undero anoikis (a form of apoptosis)
In order to metastasize, CA cells have to overcome this via changes in their membrane similar to hypoxic states
What are Paraneoplastic Syndromes?
Examples?
Caused by cancer, but not directly linked
E.g. hormones released from a tumor or an immune response triggered by the tumor that attacks the nervous system
May be the earliest symptoms of an unknown cancer
Cancer Cachexia
Caused by muscle wasting 2/2 ca deregulation
white adipose tissue (WAT) loss 2/2 thermogenesis
Appetite pathways (orexigenic and anexorgenic) pathways altered
What are the hallmarks that guide Cancer Staging
I-IV?
1: confined to orginal organ
2: locally invasive
3: spread to regional structures (lymph nodes)
4: spread to distant sites
Multigenerational Phenotype
Direct exposure of multiple generations to the same environmental factors
Transgenerational Phenotype
Transmitted to future generations through germline inheritance
Myokines
proteins release from skeletal mm during exercise that increase insulin sensitivity and can induce apoptosis in breast and colon CA cells
What are the Non-targeted Effects (NTEs) of Ionizing Radiation?
cells not directly exposed to radiation but descended from cells that are
Bystander effects
Genomic Instability
Most common cancers in early childhood
Brain Tumors
Leukemias
Most common cancers in adolescents
lymphomas
Most childhood cancers originate from the _____
mesodermal germ layer
gives rise to connective tissue, bone, etc
Embryonal Tumors
Originate during intrauterine development
These cancers often include blast cell in their name
Most common childhood cancer
ALL
Acute lymphoblastic leukemia (75% of children, 67% of adolescents)
What is MYCN? What type of cancer is it associated with?
An oncogen identified in pediatric cancer
Neuroblastoma and glioblastoma
What is Genomic Imprinting? Is it common?
Only occurs in 1% of autosomal cells
Only one allele (either the sperm of egg version) is active. The other is inactivated in ALL OF THE BODY’S SOMATIC CELLS
Biallelic
The vast majority of autosomal genes have both a maternal and paternal allele expressed
Diseases Related to Genomic Imprinting
Prader-Willi and Angelman
Beckwith - Wiedmann
Russel-Silver
Prader - Willi Syndrome
GENOMIC IMPRINTING
Inherited from Father
Short stature, truncal obesity, mental retardation, small hands and feet, small upper lip
Angelman
GENOMIC IMPRINTING
Same chromosome (15) as Prader Willi
Mother’s gene is effected
Severe ID, bouts of laughter, ataxic gait
Beckwith-Wiedmann Syndrome
GENOMIC IMPRINTING
Associated with Wilms Tumors
Caused by IGF2 Overgrowth
Identifiable at birth
Russel Silver Syndrom
GENOMIC IMPRINTING
IGF2 Undergrowth (opposite of Beckwith)
Growth retardation, small face
What is the Basic Model of Multifactorial Inheritance
Degrees of Expression
E.g. Height
Multifactorial, and tend to follow a bell curve
Threshold Model of Multifactorial Inheritance
Diseases that are BINARY but do not follow the inheritance pattern of single-gene diseases
People either have the disease or don’t, but there’s a threshold of liability, meaning the more risk factors the person has the more likely the are to express the disease
Pyloric Stenosis: Girls require more risk factors in order for the disease to be displayed than boys, so their Liability threshold is higher than for boys
Liability Threshold
Applies to Threshold model of inheritance
female babies have carry genetic markers for pyloric stenosis have a higher threshold of liability for developing the stenosis. This means they have to be exposed to more disease-causing factors to actually develop the disease. That’s why if you have a baby girl born with pyloric stenosis, there’s higher concern that future children will have it than if you had a boy and they displayed the disease.
Recurrence Risk
If my mom has it, how likely am I to get it?
E.g. heart disease: recurrence risk higher if affected relative was female and less than 55
What inherited defects play a role in colorectal CA
APC gene mutations play a role
DM1 Inheritance
Incidence higher in offspring if Father is diabetic
BMI Calculation
Weight/Height-sq
Genetic Mutations associated with early onset Alzheimer’s
Mutations that affect amyloid-beta precursor deposits
Most common is amyloid precursor protein (APP) abnormality
Mutations associated with late onset Alzheimer’s
APOE
Fragile X Syndrome
Both genetic and epigenetic
More severe in Males
ID, delyed talking, anxiety, hyperactivity, seizures
large ears, long face, prominent jaw, flat peak
Glutathione - S- Transferase
Enzyme housekeepers
Reactive to ROS to prevent damage
What is the resting potentional of nerve fibers?
-70
What is the resting potential of skeletal muscle cells?
-90
What occurs during depolarization of a nerve cell?
The cell membrane suddenly becomes permeable to sodium ions and sodium pours into the cell, reducing its negative charge
What occurs during repolarization of a cell?
Sodium channels close
Potassium channels open wide, spewing potassium out of the cell and re-establishing a negative potential
What causes activation and inactivation of the voltage gated Na channel?
When the membrane potential climbs above -55, it actually both activates AND inactivates the NA channel. The inactivation process just takes slightly longer so the gate only stays open for 1/10,000th of a second
What activates the voltage gated K channel?
K channel are actually activated when the cell membrane potential dips above -55 (just like the Na channels) but it takes slightly longer in opening, so that the K channel is opening around the same time that the Na channel is closing
What is the role of Ca ions in action potentials?
Ca serves along with (or instead of) Na in creating the membrane potential
Ca ion concentration is 10,000x greater in the ECF
What are the “fast” and “slow” channels of membrane depolarization?
Na voltage gates are “fast channels”
Ca voltage gates are “slow channels”
Sodium channels initiate action potentials
Ca channels sustain them
In what types of cells are calcium channels numerous?
Cardiac and smooth muscle
How does a decrease of extracellular calcium concentration effect nerve fibers?
Sodium channels have calcium ions attached to them. The ca’s positive charge makes the channel slightly less receptive. When calcium levels are low, the sodium channels become activated at lower thresholds, and the nerve fiber becomes “irritable”.
Only a 50% reduction in ECF Ca causes tetany!
What is the threshold of stimulation in action potentials?
-55
What is a nerve or muscle impulse?
The propagation of the action potential along a nerve (moves in both directions from the original impulse)
What is the all-or-nothing principle?
If conditions are right, once initiated an action potential will span the entire fiber. But if conditions aren’t right, it won’t be propagated at all.
What is responsible for the plateau during depolarization seen in cardiac cells?
Slow ca voltage channels maintain a longer depolarization (like the purkinje fibers)
What are the three examples of spontaneous rhythmicity in the body?
- Heart Beat
- Rhythmic Breathing
- Peristalsis
Why doesn’t re-excitation occur immediately in cardiac cells?
Hyperpolarization from potassium conductance creates a period of 1 second in which repolarization is not possible
Node of Ranvier
In myelinated axon sheaths almost no ions can diffuse through, except at the node of ranvier. The nodes are where action potentials occur.
What is saltatory conduction?
In myelinated sheaths, action potentials take place at the Node of Ranvier and are conducted through the ECF and the axoplasm from node to node along the fiber
Jumping from node to node. Faster.
What are the benefits of saltatory conduction?
- MASSIVELY Increases velocity of transmission
- Conserves energy for the axon
What is an example of mechanical excitation of an action potential?
mechanical pressure exciting sensory nerves in the skin
What is an example of chemical excitation of nerves?
Neurotransmitters
What are some examples of electrical excitation in nerves?
Electrical signals between the cells of the heart and small intestines
What mechanism creates the absolute refractory period?
Once sodium channels are inactivated, nothing except a return to the resting negative potential can reactivate them
What happens to excitability when serum calcium levels are high?
membrane permeability to sodium is decreased, and excitability is reduced
Calcium is a stabilizer
Sarcolemma
Thin membrane enclosing enclosing a skeletal muscle fiber
Myofibrils
Building blocks of muscle fibers
What are miofibrils made of?
Actin filaments (about 3000)
Myosin Filaments (about 1500)
What are actin and Myosin
large proteins responsible for muscle contraction
What is the cross-bridge cycle?
Driving force behind contraction
Interaction of thick (myosin) and thin (actin/troponin) filaments
Titin
Maintains the side by side relationship of actin and myosin
One of the largest proteins in the body
Sarcoplasm
The Intracellular fluid between myofibrils
What is in the sarcoplasm?
Potassium, Magnesium, Phosphate
Protein enzymes
mitochondria
Sarcoplasmic reticulum
Sarcoplasmic Reticulum
Regulates calcium storage, reuptake, release
What is the resting length of a sarcomere?
2 micrometers
What are the three sources to reconstitute ATP during muscle contraction?
- Phosphocreatine
- Glycolysis
- Oxidative Metabolism
Phosphocreatine
Has a phosphate bond with higher energy than ATP, so it gets cleaved and the excess phosphate replenishes ADP to ATP
What is the most efficient velocity of contraction in muscle cells?
About 30% of maximum
Motor Unit
All the muscle fibers innervated by a single nerve fiber
What are the two ways of increasing muscle contraction intensity (summation)?
- Increasing the number of motor units contracting simultaneously (multiple fiber summation)
- Increasing the frequency of contraction (frequency summation)
What is the size principle?
When a weak signal is sent from the CNS, a smaller motor unit is stimulated. As the strength of the signal grows, so does the size of the motor unit stimulated.
Tetanization
The point at which muscle contraction is smooth and continuous
What causes contractures?
In the final stages of denervation atrophy, the muscle fibers are broken down and replaced with fibrous and fatty tissue. The fibrous tissue has a tendency to continue shrinking for several months. If it isn’t actively stretched, it will contort the joint into abnormal positions.
Macromotor Units
When some but not all nerve fibers to a muscle are destroyed, the remaining fibers will form new axons to the paralyzed fibers
Won’t regain the same level of control, but will be able to use the muscle
polio
Why does Rigor Mortis occur?
ATP is required to separate the cross bridge from the actin filament. After death the muscles contract without action potentials until the proteins deteriorate at 15-20 hours later
Mesenchymal Stem Cells
nonhematopoietic
bone, cartilage and fat cell production
Which bone marrow produces blood cells?
skull
vertebrae
ribs
sternum
shoulders
pelvis
Osteo -
Chondro -
Myo -
Stromal -
Bone
Cartilage
Muscle
Marrow
What three types of cells are found in bone?
- Osteoblasts
- Osteocytes
- Osteoclasts
Osteoblasts
Mesenchymal Origin
Initiate bone formation
deposit calcium and collagen to form a matrix called osteoid
Osteocytes
Differentiated osteoblasts
most abundant
mechanoreceptors that sense bone loading, stress etc
Communicate with other bone cells to guide formation and resorbtion of bone
Osteoclasts
Hematopoeitic
migrate over bone surfaces, breaking down areas that have been stripped of osteoid
How does calcitonin suppress bone resorption?
It binds with osteoclasts’ receptors, knocking them off the bone’s surface
OPG/RANKL/RANK System
RANKL increases bone loss by proliferating osteoclasts
OPG is secreted by osteoblasts and B lymph, binds to RANK so RANKL can’t
If the two get out of sync, you get problems
What are the two types of Bone?
Compact bone tissue (85%)
Spongy bone tissue (15%)
What is the axial skeleton?
80 bones
skull, vertebral column, thorax
What is the appendicular skeleton?
126 bones
Upper and Lower Extremities
Shoulder (pectoral) girdle
Pelvic girdle (os coxae)
Ground Substance
Gelatinous material found in bone
Harversian System
Structural Unit of Compact Bone
Components of Long Bone
Epiphysis (broad end)
Diaphysis (long narrow portion)
Metaphysis (neck)
Remodeling
Osteoclasts take bone apart
Obsteoblasts deposit new bone
What are the 5 stages of bone repair?
- Hematoma formation (hours)
- Procallus formation (days)
- Callus formation (weeks)
- Replacement
- Remodeling (years)
Synarthrosis
Immovable Joint
Amphiarthrosis
Slightly moveable joint
Diarthrosis
Freely movable joint
Syndesmosis
Fibrous Joint
two bony surfaces connected by a ligament or membrane
Radial-Ulnar
Tibial-Fibial
Gomphosis
Fibrous Joint
Conical projection fits into a socket
Teeth
Symphysis
Cartilagenous Joint
Bones united by pad or disc of cartilage
Symphysis pubis
intervertebral discs
Synchondrosis
Connected by hyaline cartilage
Ribs
Three terms that describe skeletal muscle
Voluntary (controlled directly by the CNS)
Striated (striped under the microscope)
Extrafusal
Where do the axons of motor nerves originate?
Anterior horn cell of the spinal cord
Motor Unit
Consists of a single motor neuron and ll the skeletal muscle fibers it innervates
Neuromuscular Junction
Junction between the axon of the motor neuron and the plasma membrane of the muscle cell it’s acting on
Ryanodine Receptors
Primary ion channel controlling calcium release in the sarcoplasmic reticulum
What are the four steps of muscle contraction?
- Excitation
- Coupling
- Contraction
- Relaxation
What happens during the coupling phase of muscular contraction?
Calcium ions released by ryanodine receptors couple with troponin
When does muscular relaxation begin?
When calcium ions move back into the sarcoplasmic reticulum
Sarcopenia
Age related loss in skeletal muscle
Which declines faster after age 50: muscle strength or muscle mass?
muscle strength
Synaptic Cleft
The space between the axon (nerve cell) and the muscle cells, where acetylcholine is transferred
20-30 nm wide
This is where acetylcholinesterase resides
Where is acetylcholine synthesized?
In the cytoplasm of the axon terminal, then rapidly formed into synaptic vessicles
What stimulates acetylcholine release from the axon active site?
Calcium!
Subneural cleft
clefts in the muscle cell membrane where acetylcholine interacts with the muscle cell
Lined with acetylcholine gated channels
and Na voltage gated channels
End plate potential
When acetylcholine interacts with the acetylcholine gated ion channels, sodium pours into the cell creating a positive charge that lowers the threshold below -55 and triggers voltage gated sodium channels
What does the high safety factor of the neuromuscular junction refer to?
each impulse that arrives at the neuromuscular junction causes about three times as much end plate potential as that required to stimulate the muscle fiber
What organic insecticide is particularly lethal to humans because it inhibits acetylcholine for WEEKS?
diisopropyl fluorophosphate
How do nerve impulses penetrate deep into muscle fibers?
T Tubules - they are essentially extensions of the cell membrane
The T tubule action potentials cause release of calcium ions inside the muscle fiber in the immediate vicinity of the myofibrils, and these calcium ions then cause contraction
Fusiform Muscles
Long and slender
Pennate Muscles
Fan Shaped
“KUSSMAL”
Ketones
Uremia
Salyciates
Sepsis
Methanol
Aldehyde
Lactic Acid
What diseases would cause an elevated anion gap metabolic acidosis
Lactic Acidosis
Ketoacidosis
Uremia
Methanol/Ethylene Glycol
Salycilates
Paraldehyde
What disease could cause a normal anion gap metabolic acidosis?
Anything where Bicarb is being lost and Cl is being reabsorbed
Renal Tubular Acidosis
GI Losses
Carbonic Anhydrase Inhibitors
What’s the difference between eukaryotes and prokaryotes?
Prokaryotes have no organelles and thus no nucleus
The outer membrane of the nucleus is continuous with the _________
endoplasmic reticulum
What causes DNA to fold into chromosomes?
Histones
Where is protein primarily synthesized and broken down?
cytoplasm
Where are ribosomes synthesized?
the nucleus, then float out through NPCs to cytoplasm or rough ER
What is the function of the rough endoplasmic reticulum?
membrane factory
synthesizes the proteins and lipids needed for membranes both of the cell and organelles
What is the function of the smooth ER?
- synthesis of steroid hormones
- removing toxic substances from the cell by communicating with the golgie complex, lysosomes and peroxisomes
What is the role of the golgi complex?
Stores secretory vesicles, stacked like pancakes
a refinery of substances that will ultimately be released from the cell or form lysosomes
What type of disease are lysosomes often associated with?
disease leading to cellular injury and death
What are the four pathways of degradation in lysosomes?
endocytosis
phagocytosis
macropinocytosis
autophagy
What is endocytosis?
Uptake of macromolecules from the ECF
What is phagocytosis?
Uptake of large particles or microorganisms by phagocytic cells (macrophages and neutrophils)
What is Macropinocytosis
nonspecific uptake of fluids, membrane and particles attached to the membrane
What is autophagy?
Cellular self destruction
begins in the cytosol and is used to digest cytosol and ineffectual organelles
When does a primary lysosome become a secondary lysosome?
lysosomes maintain a relatively neutral pH until they are activated by binding with a vacuole or organelle, with converts it into a highly acidic internal environment (secondary status)
What are peroxisomes?
Similar to lysosomes, but they use oxygen
Oxidative reaction produces peroxide
Catalase uses the hydrogen peroxide to oxidize alcohols
important in detoxifying cells
Where in mitochondria does the respiratory chain take place
Inner membrane
What takes place in the mitochondrial matrix?
Metabolism of carbs, lipids, amino acids
Where does most cellular metabolism take place?
Cytosol
Where is extra glucose stored?
converted into glycogen in the cytosol
forms a temporary mass called an inclusion
What is mechanotransduction?
Performed by cytoskeleton
Translates mechanical stimuli into biochemical signals
Allows cell to adapt to their surroundings
What is the function of microtubules?
add strength
moves organelles
moves pretty much anything in the cell that needs to move
What’s the difference between flagella and cilia
Flagella move the cell
cilia moves things around the cell, cell stays stationary
both involve microtubules
What are glycolipids and glycoproteins?
Both found on membranes
carbs and lipids: glycolipids
carbs and proteins: glycoproteins
Why are lipids said to be amphipathic?
Fancy word for polar
hydrophobic: uncharged
hydrophilic: charged
What are transmembrane proteins?
Proteins that sit in the membrane and create an aqueous pathway between ECF and ICF
What are the three ways proteins move through the cytosol?
Gated transport (NPCs)
Protein translocation
Vesicular Transport
Proteostasis
protein regulation
What are four examples of proteolytic cascades?
Caspase mediated apoptosis
coagulation cascade
degrading membrane enzymes
complement cascade
What are proteases?
Enzymes that break down proteins
What is the glycocalyx?
The cell coat
Formed by carbohydrates
What does the glycocalyx do?
Protects cell from mechanical damage
creates a slimy surface that helps with motility
cell-to-cell recognition and adhesion
What is a ligand?
small molecule that bind to the cellular receptor proteins
hormones are ligands
What are three ways cells are held together to form tissues?
- extracellular matrix
- cell adhesion molecules
- specialized cell junctions
What is the basal lamina, and what kind of cells have it?
type of extracellular matrix
thin, tough, flexible
lies beneath epithelial cells, over muscle cells, fat cells, schwann cells
What are the four major roles of the ECM?
mechanical support
control of cell proliferation
formation of scaffold for regeneration
tissue microenvironment
What are cell adhesion molectules (CAM)
cell surface PROTEINS that bind cells both to eachother and to the ECM
TIght junctions
barriers to diffusion
prevent movement through membranes and leakage out
Gap junctions
communicating tunnels from one cell to another
Why does increased cytoplasmic calcium cause decreased permeability of the junctional complex?
Because dying cells release calcium, so when there’s increased calcium the cells shut down to protect themselves
What happens when a ligand binds to a receptor protein?
Signal transduction!
The message from the extracellular messenger (first messenger) is transferred to the internal messenger (second messenger)
The second messenger triggers a cascade
What is the difference between electrolytes and nonelectrolytes
Electrolytes dissociate into ions when placed in a solution
nonelectrolytes do not (glucose, urea, creatinine)
What are the three types of passive transport?
Diffusion
Filtration
Osmosis
What is the difference between diffusion and osmosis?
Diffusion is the movement of a SOLUTE MOLECULE down its concentration gradient
Osmosis is the movement of WATER down a concentration gradient
What is filtration?
Movement of water and solutes due to pressure/force
Glomerular filtration is driven by blood pressure
Which substances diffuse rapidly across the cell membrane?
Nonpolar, lipophilic substances:
CO2, O2, steroid hormones, fatty acids
What substances diffuse very slowly across the cell membrane?
Water soluble substances:
sugars, inorganic ions
IONS ARE POLAR. THAT’S WHY IT’S SO HARD FOR THEM TO DIFFUSE
If water soluble substances find it difficult to get through the membrane, why can water readily diffuse through the cell membrane?
the dipolar structure of water allow it to cross the lipid bilayer easily
What is osmotic pressure?
The amount of hydrostatic pressure required to oppose the osmotic movement of water
What is the osmolality of an isotonic solution?
285 mOsm/kg
What percentage of cellular ATP produced is used for Na-K ATPase?
60-70%
How do sugars and amino acids get across the cell membrane?
Sodium dependent symport
What’s the difference between pinocytosis and phagocytosis?
Pinocytosis is the taking up of specific macromelecules for use or metabolism (like antigen presenting cells)
Phagocytosis is bring something in specifically to eat it
Both require energy
What are somatic cells
Anything that isn’t sperm or eggs
What two factors determine a cell’s progress through the cell cycle
Cyclin-dependent kinases
Cyclins
What is a mitogen?
extracellular signal molecule that stimulates mitosis
What are cytokines?
Growth factors
Hypertrophy
Increase size of cells due to increased work demands
Hyperplasia
Increased NUMBER of cells caused by increased cellular division
Regeneration, pregnancy
Dysplasia
Abnormal change in size, shape or organization of mature tissue cells
Differ from cancer in that they don’t involve entire thickness of epithelium
Metaplasia
reversible replacement of one mature cell type with another less differentiated cell type
What are the components of R-A-A
Renin: enzyme released from kidney
Angiotensin 1: Inactive polypeptide
Angtiotensin 2: ACE in lungs converts, causes vasoconstriction
Aldosterone: Retains sodium, excretes K
Hypovolemic Hyponatremia
loss of body sodium AND greater loss of water
loop diuretics
osmotic diuresis (DKA, mannitol)
GI losses
non-concentrated urine in kidneys
Euvolemic Hypernatremia
MOST COMMON
Why does hypokalemia cause membranes to become hyperpolarized?
Potassium diffused freely out of the membrane, so if ECF levels drop suddenly, potassium leaves and the cell develops a more negative charge and is more difficult to excite
What happens to cell polarity with hyperkalemia?
Hypopolarized (becomes more positive), easier to excite
What is Chvostek’s Sign
Hypocalcemia
Facial Nerve
Trousseau Sign
Does hypocalcemia increase or decrease excitability?
Increases
BECAUSE it decreases the threshold potential
Why does giving calcium protect the heart from loss of function during hyperkalemia?
An increase in serum potassium will increase (make less negative) the resting potential of the cell membrane. This means the cell needs less positive stimulation to reach the threshold potential and depolarize.
Giving calcium increases the threshold potential, so that even though the resting potential is altered, it will still take a large amount of positive ions to cause a depolarization
Why would respiratory aklalosis from hyperventilation cause hypophosphatemia?
It increases ATP use, decreasing phosphate
How does hydrogen transport through the cell membrane occur?
Primary active transport in gastric glands and distal tubule
Secondary active transport via Sodium-hydrogen countertransport in the proximal tubules
How is calcium transported across the cell membrane?
Active transport through calcium pump
Secondary active transport through na-ca countertransport
How do glucoses and amino acids cross the cell membrane?
Secondary active transport via co-transport with Na
What are codons?
All amino acids are specified by triplets of bases called codons
How is the end of a gene identified?
By stop or nonsense codons.
3 of the 64 possible codons are stop codons
Why is the genetic code said to be redundant?
There are 61 codons that code for AAs in the body, but only 20 different types of amino acids
In DNA Adenine pairs with _______
Guanine paires with ______
Thymine
cytosine
DNA polymerase
travels alongside the single DNA strand, adding nucleotides and proofreading
What is a missense mutation?
Base pair substitution that alters a single amino acid
What is a nonsense mutation?
base pair substitution that results in any of the three stop or nonsense codons
What is the difference between a frameshift mutation and a base pair substitution
In a base pair substitution, the number of base pair isn’t altered, one of them is just different, so the rest of the strand isn’t affected
with frameshift mutations, it alters the way the entire strand is read by inserting or deleting an entire base pair
What are the purines and pyrimidines?
Purines: Adenine and Guanine
Pyrimidines: Thymine/Uracil and Cytosine
When does transcription begin?
When RNA polymerase binds to the promoter site of a DNA sequence (gene)
What does transcription stop?
When a termination sequence codon is reached
What are introns and exons?
Introns are the excised bits that are not translated
Exons are translated
What are miRNA
noncoding RNA (introns) that bidn to specific mRNA sequences and down regulate their expression
What is a polypeptide?
A chain of amino acids
The building block of a protein
Mutations in only one kind of cell can be transmitted to offspring. Which kind?
Germine cells aka gametes
somatic cells DO NOT pass on mutations
What are haploid and diploiod cells?
Gametes are haploid cells: they only have one member of each chromosome pair
Somatic cells are diploid: they have complete chromosome pairs
What are autosomes?
The chromosomes that are not sex linked
Which chromosomes are homologous?
Means each side of the chromosome is identical. All autosomes are homologous. The x chromosome is homologous.
THE X AND Y CHROMOSOME ARE NOT HOMOLOGOUS IN MALES
What is the euploid form of a gamete and a somatic cell?
“Normal”
a haploid gamete and a dipload somatic cell
What’s the difference between aneuploidy and polyploidy?
Aneuploidy is the presence of an extra chromosome
Polylploidy is the presence of an extra chromosome piece (three copies of a chromosome instead of two). There are still the same number of chromosomes.
Is trisomy 21 an aneuploidy or a polyploidy?
Aneuploidy. There is an entire extra chromosome.
Why aren’t there disease associated with monosomy?
It’s lethal
What’s more serious: an aneuploidy in an autosome or a sex chromosome?
Autosome
What are the three trisomies seen in live children?
13, 18, 21
What usually causes a trisomy?
nondisjunction: failure of the chromatids to separate during meosis or mitosis
Turner Syndrome
Sex chromosome aneuploidy
No y or second x chromosome
They are ALWAYS female
Sterile, webbed neck, coarctation of aorta
Klinefleter
Sex chromosome aneuploidy
At least two x chromosomes and a Y
Degree of pentrance increases with number of extra x’s
small testes, gynecomastia, sterile, male appearance
Cri du chat
chromosomal deletion on chromosome 5
ID, LBW, hear defects
What is unique about chromosomal abnormalities leading to inversions?
Usually don’t affect the individual, but their offspring will often have duplications or deletions that ARE harmful
Which is more harmful: a deficiency of genetic material or an excess?
A deficiency. This is why deletions are more harmful that duplications
What is a translocation?
Interchanging of genetic material between non-homologous chromosomes
What is fragile X?
a fragile site on the x chromosome associated with ID
Describe the alleles of heterozygous and homozygous individuals?
At a given locus on each chromosome, one is from mother and one is from father. If mom and dad’s are identical, they’re homozygous. If not, heterozygous.
Penetrance
percentage of individuals with the gene who also express disease (phenotype)
What is the most common and severe x-linked recessive disorder?
DMD!
Recurrence risk becomes higher if:
- More than one family member is affected
- The expression of disease in the proband is more severe
- The proband is of a less commonly effected sex
Aberrant DNA methylation is responsible for misregulation of ______ and ______
Tumor suppressor genes
oncogenes
What epigenetic mechanism is responsible for x inactivation?
DNA methylation
What is a nucleosome?
A set of histones and the segment of DNA wound around them
What does heterochromatic mean?
Epigenetically blocked and inaccessible by transcription factors
DNA methylation and histones impact _______
miRNA impact _______
transcription
translation
Imprinted genes are likely to control what?
Organismal growth
If maternal version expressed, offspring generally smaller
If paternal version expressed, offspring generally larger
Which gene (maternal or paternal) codes for brain development in chromosome 15?
maternal. That’s why angelman (where maternal deletion is inherited) results in severe ID
Which two disease are the result of aberrant imprinting on chromosome 11?
Beckwith-Weidman (overexpression of IGF2 = fat)
Russel-Silverman (underexpression of IGF2 = tiny)
Paternal gene contains IGF2 gene, so in BW it’s doubled (no maternal present)
In RS no paternal present, so IGF2 low
What happens to methylation as tumors progress?
Methylation density steadily declines in as tumors progress
In cancer, the promoter regions of tumor-suppressor genes are _______
hypermethylated (inhibited)
What are two examples of growth/tumor suppressor genes?
Tp53
RB (retinoblastoma) gene
What do Burkitt’s Lymphoma and CML have in common?
Both due to translocations
_____ is the intrinsic trigger for apoptosis
______ is the extrinsic trigger
TP53
Fas/FADD
When is surgery used in cancer treatment?
Non-metastatic
palliative
Cancer development due to chronic inflammations is due to what factors?
ROS
COX-2
5-LOX
MMPs
transcription factors
Developmental Plasticity
Degree to which an organism’s development is contingent on its environment
how does botulism effect acetylcholine?
Blocks release of acetylcholine
How does nerve gas alter acetylcholinesterase
Blocks its function
What are spindles?
mechanoreceptors on mm cells that respond to muscle stretching
Golgi Tendon Organs
dendrites that terminate and branch to tendons near the neuromuscular junction
Sense stretching?
Neuregulin
increase the number of Ach receptors
helps in formation of spindles
RyR1
skeletal muscle
RyR2
cardiac muscles
RyR3
diaphragm, smooth muscle, brain
Articular cartilage is made up of what two things?
Collagen (anchors cartilage to bone)
Proteoglycans (control the loss of fluid from the cartilage)
What age groups have the highest incidence of fractures?
Males 15-24
Adults > 65
What kind of fractures are more prevalent in women?
Hip and wrist
complete fracture
integrity of bone is broken into two pieces
comminuted fracture
breaks into more than two pieces
Three types of incomplete fractures
greenstick
buckle (torus)
bowing (common in kids)
Fragility Fracture
often due to osteoparosis
results from trauma that wouldn’t normally cause a fracture
pathologic fracture
break at the site of a pre-existing abnormality (like a cancer)
Simple vs complex dislocation
Simple: doesn’t involve a bone break
complex: associated fracture
Difference between a sprain and a strain
Chondrosarcoma
2nd most common malignant bone tumor
ill defined tumore that infiltrates trabeculae in spongy bone, usually metaphysis or diaphysis
Fibrosarcoma
Collagenic tumor
Solitary tumor in metaphyseal region of femur or tibia
Osteosarcoma
Osteogenic (bone forming)
38% of bone tumors
Usually persons less than 20yo
Giant Cell Tumor
Myelogenic tumor (bone marrow cells)
benign, solitary, circumscribed
cause extensive bone resorption
overexpression of OPG
How do glucocorticoids effect bone density?
Decrease density
increase RANKL expression by inhibiting OPG production
Osteoarthritis is characterized by ____ (3)
loss of articular cartilage
sclerosis of underlying bone
formation of bone spurs (osteophytes)
What organs does RA affect?
heart/lungs,
kidneys
skin
joints
What is ankylosing spondilitis?
stiffening and fusing of spine and sacroiliac joints
Is ankylosing spondilitis caused by inflammation of the connective tissue?
No. Caused by synovitis and bone marrow inflammation
The greater the innervation ratio, the greater its:
endurance
higher innervation ratios
vs
lower innervation ratios
higher: prevent fatigue
lower: provide precision of movement
Dynamic contraction
muscle maintains a constant tension
length changes
Isometric
maintains a constant length while tension increases
