Patho/Physio Exam 1

Passive Process

no cellular energy required

substances move DOWN concentration gradient

not charged molecules

Diffusion

passive process

movement of small/lipophilic molecules down conc. gradient

Osmosis

passive process

movement of water across semipermeable membrane

small amounts of water can go through phospholipids

large amounts go through kidney (ie kidney)

Simple Diffusion

passive process

NO transport protein required

solutes move down conc gradient

Rate of Diffusion

depends on

1. steepness of conc gradient (steeper = faster)

2. temperature (higher temps = faster)

3. thickness of membrane (thicker = slower)

Facilitated Diffusion

transport PROTEIN required

solutes move down conc gradient

(channel/ carrier)

Channel Mediated

facilitated diffusion

moves small polar molecules high —> low still

CARRIER protein

Carrier Mediated

Small polar molecule moved by carrier PROTEIN

high —> low still

facilitated diffusion

specific to given molecule(s)

may be competiton for similar carriers/ molecules

number of carriers is limited (saturation); rate of transport increases until concentration is reached

Active Transport

require expenditure of cellular energy

ion/small molecule moved against conc. gradient

Primary Active Transport

energy source from ATP

low —> high

Secondary Active Transport

Energy source from movement of ANOTHER substance

Symport

type of secondary active transport

two substances moved in same direction

Antiport

type of secondary active transport

two substances moved in opposite directions

Vesicular Transport

involves a vesicule

exocytosis/ endocytosis

Exocytosis

vesicle releasing its contents from cell

vesicular transport

Endocytosis

vesicle is formed as material is brought into a cell

vesicular transport

Transcytosis

vesicle taken in on one side of a cell, moved across the cytoplasm inside vesicles, and released on the opposite side

Phagocytosis

cell uses its outer membrane to engulf and digest large solid particles or harmful pathogens

endocytosis

Pinocytosis

a cellular process where a cell engulfs extracellular fluid and dissolved solutes by folding its plasma membrane inward

“cellular drinking”

endocytosis

Receptor-Mediated Endocytosis

receptor required

very specific

substance binds to protein receptor and gets engulfed

SGLT2 co-transporters in Kidneys

Na+/ Glucose symporter reabsorbs glucose back into bloodstream to avoid waste until tm (conc. max) is reached

Tm —> glucose excreted in urine

Tonicity

ability of a solution to change the volume/pressure of a cell by osmosis

Isotonic Solution

interstitial fluid is same as cytosol

no net water movement

no change in volume

Hypotonic Solution

interstitial fluid is LESS concentrated than cytosol

water ENTERS cell

hemolysis

why water cannot be infused

Hypertonic Solution

interstitial fluid is MORE concentrated than cytosol

water LEAVES cell

crenation/ cell shrivels

Tight Junction

impermeable junctions that prevent molecules from passing through intercellular space

made of claudin (form the actual seal/barrier) and

occludin (helps stabilize and regulate the seal)

Desosomes

anchoring junctions bind adjacent cells together like molecular velcro + help form internal tension-reducing network of fibers; for strength

made of keratin (intermediate filament)

and cadherins (linker proteins)

Gap Junctions

communicating junctions allow ions and small molecules to pass for intercellular communication

connexons form channels between cells

Electrical Signals

changes in the membrane potential of a cell

cell-to-cell communication; phsiological signals

Chemical Signals

secreted by cells into extracellular fluid

responsible for most communication in body

occurs via ligands

Contact-Dependent Signals

require interaction between membrane molecules on two cells;
“fingerprint access”

local communication

Gap Junctions

form direct cytoplasmic connections between adjacent cells

local/ electric communication

Autocrine Signals

act on same cell that secreted them

local/electric cell communication

occurs via ligand binding

Paracrine Signaling

secreted by one cell and diffuse into adjacent cells via ligand binding

local/electrical cell communication

Long Distance Communication

nervous system uses chemical and electrical signals

Neurocrines

chemical signals secreted by neurons

Neurotransmitters

chemicals secreted by neurons that diffuse across a small gap to the target cell

gets released then travels

Neurohormones

chemicals released by neurons into blood for action at distant targets

only act on targets/ receptors

Cytokines

mediate inflammation

peptides

synthesized and secreted by all nucleated cells in response to stimuli

involved in autocrine, paracrine, endocrine signaling

e.g. interleukins and TNFa

Electrical Potential/ Electrical Current

number of ions is different across the membrane

plasma membrane provides a resistance to ion flow

Role of Ion Channels

to allow passage of ions in/out of cells

passive, leakage channels —always open

ligand gated channels—open with binding of specific NT/ ligand

Ligand Gated Ion Channel

1. channel = closed until NT binds to it

2. open channel permits DIFFUSION of specific ions post binding

passive/ facilitated transport

eg. ACh binds —> Na+/K+ molecules pass through CHANNEL bc charged, ACh removed, channel closes

Voltage Gated Channels

open and close in response to membrane potential changes; once threshold is reached

channel opens when voltage changes

Resting Membrane Potential

-70 more K+ inside, more Na+ outside (inside more negative than outside)

generated by different concentrations of Na+, K+, and protein anions (A-)

Na+/K+ channels= closed

inactivation gate open, activation gate closed

Depolarization

inside of membrane becomes more positive —> may lead to action potential

Na⁺ IN, Ca+ IN (move high —> low ), K+ gate closed

threshold is reached (-50 to -55 mV)

depolarization becomes self-generating (all-or-nothing)

Repolarization

membrane returns to resting membrane potential (-70)

K⁺ OUT, permability to Na+ decreases to resting levels

internal negativity restored

ionic redistribution back to resting conditions is restored by Na+/ K+ pump

Hyperpolarization

inside of membrane becomes more negative that resting membrane potential

K+ OUT for longer (excessive efflux), Cl- IN, Ca+ OUT

insensitive to stimulus and depolarization at this time

Graded Potentials

needs stimulus not threshold

short lived

insentity decreases with distance

the stronger the stimulus, the bigger the graded potential

local current flow

bi-directional (hyperpolarization/ depolarization)

can sum together

Action Potentials

long distance signals

all-or-nothing, maintained through length of axon

jump from node to node if myelinated, regenerated at each neighboring section of membrane for unmyelinated

only depolarization

Absolute Refractory Period

prevents neuron from generating AP

ensures each AP is separate

enforces one-way transmission of nerve impules

Relative Refractory Period

neuron can be restimulated but needs stronger stimulus

occurs during hyperpolarization

Na+ gates closed, K+ open, repolarization is occuring

Conduction Velocities of Axons

the wider the axon the faster

the presence of a myelin sheath dramatically increases impulse speed

Synapses

a junction that mediates information transfer from one neuron to another/ to an effector cell

two types: electrical and chemical

Electrical Synapses

less common than chemical synapses

correspond to gap junctions in other cell types

allow ions to flow from one neuron to the next

rapid speed

important for awakeness after sleep, mental attention, emotions and memory, ion and water homeostasis in brain (astrocytes)

Chemical Synapses

specialized for the release and reception of neurotransmitters

composed of

axon terminal of presynaptic neuron which contains synaptic vesicles

receptor region on the dendrites or soma of postsynaptic neuron

Ca+ channels open, Ca+ enters, Ca²⁺ causes neurotransmitter vesicles to release neurotransmitter, NT binds receptors on the postsynaptic cell, produces response

Synaptic Cleft

fluid-filled space separating the presynaptic/postsynaptic neurons

prevents nerve impulses from directly passing from one neuron to next

unidirectional communication between two neurons

Neuromuscular Junction

action potential

depolarization opens Ca+ channels

Ca²⁺ rushes INTO the presynaptic terminal

Ca²⁺ triggers vesicle fusion (vesicle is already docked/primed by the SNARE complex)

Vesicle fuses with membrane

ACh is released by exocytosis

SNARE proteins

Synaptobrevin (vesicle)

Syntaxin (Presynaptic membrane)

SNAP-25 (Presynaptic membrane)

Synaptobrevin

located on vesicle

docking station; attaches membrane + vesicles

(brevin —> bring in)

Syntaxin

located on receptor/ presynaptic membrane

binds synaptobrevin and helps anchor/fuse vesicle

(SYNtaxin —> SYNthesis together)

SNAP-25

located on receptor/ presynaptic membrane

works with syntaxin to bind synaptobrevin and drive fusion

EPSP

excitatory post-synaptic potential

graded potential (more stim —> more signal)

depolarizes towards threshold

Na⁺ IN (sometimes Ca²⁺ IN)

IPSP

inhibitory postsynaptic potential

usually hyperpolarizes or stabilizes membrane

moves membrane away from threshold; makes AP less likely

Cl⁻ IN or K⁺ OUT

Termination of Synaptic Transmission

NT bound —> continuous postsynaptic effect + blocks reception of additional messages

NT removal —> degraded by enzymes, reabsorbed by astrocytes (regulatory glial cells) or the presynaptic terminal, diffuse from synaptic cleft

Agonist

ligand

fully turns ON effects of cell

Antagonist

ligand

effectively blocks effects/ response of cell; prevents an agonist/natural ligand from activating the receptor

Partial Agonist

ligand

binds and partially activates

becomes antagonist in presence of antagonist

drugs for opioid use disorder (provide enough opioid-receptor activity to reduce withdrawal symptoms and cravings but does not have full effects)

Inverse Agonist

binds to receptor and decreases/ lessens activity; actively pushes the receptor toward its inactive state; opposite activity

benadryl (lowers activity of histamine receptor, causes drowsiness bc histamine also provides awakeness reponse and that is reversed)

Second Messengers

cAMP (example)

1. ligand binds to receptor

2. activates enzyme that produces cAMP from ATP

3. cAMP activates other enzymes

4. cell activites change in response

functions: open/close channels, activate kinase enzymes, phosphorylate + activate proteins, activate genes + induce protein synthesis

Polar ligand/ receptor

water soluble —> cannot cross membrane so uses extracellular receptor

uses second messengers; inside cell (reacts inside)

Non-polar ligand/ receptor

lipid-soluble —> intracellular receptor (activates nucleus)

e.g. steroid hormone (cortisol or estrogen)

comparison of receptor signaling

ion channels have the fastest signal transduction speed + onset of action but shortest duration of action

g-protein coupled: fast (but not fastest) signal transduction speed + onset of action, medium duration of action

steroid/nuclear: slow signal transduction speed + onset of action but longest duration of action; only nonpolar molecules

:. ion channels fastest, steroids longest DOA

Gs (G-protein activation)

stimulatory

1. ligand binds to GCPR

2. changes protein shape causing GDP to leave and GTP to bind

3. α-GTP and βγ parts separate

4. αs activates adenylyl cyclase

5. adenylyl cyclase makes cAMP from ATP

6. adenylyl cyclase carries/amplifies signal inside the cell bc ligand is polar

7. cAMP activates PKA (enzyme that phosphorylates proteins)

Gi (G-protein activation)

inhibitory (adenylyl cyclase; cAMP and PKA inhibited)

1. ligand binds to GCPR

2. changes protein shape causing GDP to leave and GTP to bind

3. α-GTP and βγ parts separate

4. αs inhibits adenylyl cyclase (no cAMP activation, no PKA activation)

Gq (G-protein activation)

1. ligand binds to GCPR

2. changes protein shape causing GDP to leave and GTP to bind

3. α-GTP and βγ parts separate

4. αs activates phospholipase C

5. PLC cleaves a phospholipid in the cell membrane called PIP₂ —> makes IP₃ and DAG (second messengers)

   1. IP₃ goes to ER and releases Ca+ into cell cytoplasm

   2. DAG stays in membrane and activates protein kinase C (PKC) (Ca+ production also helps activate)

General Adaptation Syndrome

systemic adaptation to exposure to a stressor resulting in physical manifestations (changes) that are coordinated and interdependent (many organs involved)

Three Stages of GAS

1) Alarm: occurs right away, activates sympathetic system, releases cortisol

2) Resistance: intermediate phase; body tries to use most effective/efficient means to withstand stress

3) Exhaustion: defense resources run out, injury pursues (leads to possible disease + death)

Disease

any process that causes the inability of an individual to adapt to their environment and maintain homeostasis

threatens survival of organism

causes impaired bodily function, cellular changes, inflammation, and pain

Etiology

the cause of a particular disease, includes both intrisic (within patient) and extrinsic factors (virus-caused)

can help w disease prevention, early identification/screening, theraputic strategies or may be idiopathic (cause unknown)

Infectious (Disease Category)

caused by pathogens such as viruses, parasites, fungi, bacteria

Degenerative (Disease Category)

caused by wear-and-tear, aging, or trauma

Neoplasia (Disease Category)

cancer; abnormal, uncontrolled cell growth

Immune Disorders (Disease Category)

immune system definciencies, allergies, AI disorders

Metabolic Disorders (Disease Category)

caused by lack of enzymes

hereditary disorders

Malnutrition (Disease Category)

cause by a lack of vitamins/ nutrients

Hormonal Disorders (Disease Category)

caused by imbalance/ abnormal amount of hormones

Mental/Emotional Disorders (Disease Category)

depression, anxiety, schizophrenia

Atrophy

Tissue wastes away

cells decrease in size not die

caused by inactivity (not using muscle), denervation (electrical signal going away), inadequate nutrition, aging (decreased muscle mass), lack of hormones, decreased blood flow (no nutrients brought)

cytoskeleton breaks down via ubiquitin-proteasome system (tag + protein-destroyer)

apoptosis may be triggered

Hypertrophy

cells increase in size not number

caused by increase in workload, excessive hormonal stimulation

(hyperTROPHY —> body builders want)

Hyperplasia

increase in cell number

results in increased tissue mass

may be compensatory mechanism for metabolic demands

excessive hormonal stimulation

Metaplasia

one mature cell type is replaced by another (weaker for stronger)

reversible; if stimulus stops, cells go back to original type

caused by chronic inflammation/irritation

may be associated with higher cancer risk

eg) Barrets Esophagus

Dysplasia

cells mature abnormally within a tissue such that cells vary in shape, size, and organization

large nuclei

increased rate of mitosis

caused by chronic irritation

pre-cancerous

Anaplasia

cells become undifferentiated (don’t look like original)

nuclei become very large and stain very dark

multiple cells undergo mitosis

associated with cancer/malignancy

Intracellular Accumulations

build up of substances (lipids, proteins, melanin, bilirubin/exogenous substances) in nucleus, cytoplasm/ lysosomes

accumulation may be transient or permanent

may be harmless or toxic

substances: unused foods, lipids, glycogen, pigments, calcium salts

Neoplasm

new growth/mass

causes lump/tumore

occurs when cell ignores normal controls of cell division (contact inhibition) and multiplies excessively

can either be benign or malignant

Hypoxia/ Ischemia (Injurious Agent)

Hypoxia = not enough O₂

Ischemia = not enough blood flow

both lead to ATP depletion

—> decrease of Na+/K+ ATPase pump —> accumulation of Na+ and water inside cell,

lactic acid build up (bc anaerobic respiration),

detached ribsosomes —> decreased protein synthesis

Reactive Oxygen Species (ROS)

ROS = chemically destructive molecules

excessive ROS causes oxidative damage to cell structures + DNA

usually: SOD (superoxide dismutase) converts O2 to H2O2 (still toxic) catalase/ glutathione peroxidase (using GSH) makes H2O2 into H2O

Glutathione reductase + NADPH: regenerates GSH

Sublethal Morphological Changes

biochemical changes —> hard to see

morphological changes —> can be seen under a microscope (cellular swelling: hydropic/ fatty changes)

Fibrosis

replacement of damaged cells with scar tissue

holds organs together but does not restore normal function

Necrosis

associated with disease process/ injury

injured beyond repair

occurs with lack of ATP

unregulated process; cells + organelles swell and rupture + leak out

needs to be removed to prevent spread