physio module one

Stratified epithelial tissue

provides protection, held together by structures called intercellular junctions (junction complexes)

• to close together to house blood vessels, nourished by connective tissues beneath

• epithelial tissues are attached to connective tissues by a basement membrane

Nonkeratinized membranes

• have living cells in all layers

• reproduce and other func.

Keratinized

• have cells filled with keratin: a water resistant protein: and layers of dead cells on the surface

• epithelial membranes continually renew by losing surface cells and replacing with new cells

Exocrine Glands

• derived from epithelial tissues

• secretions are transported by ducts (main difference between exo and endo)

  • ex: lacrimal, sweat, sebaceous glands, digestive enzymes, and prostate

• secretory portions may be tubes or acini groups

• usually simple cuboidal (not always; columnar in respiratory)

Sweat Glands

1. Eccrine or merocrine: more numerous; secrete a salty sweat; involved in thermoregulation (simple)

2. Apocrine: located in axilla and pubic reg

   ion; protein-rich sweat that bacteria feed on (more acinar/branched)

Endocrine Glands

• derived from epithelial tissues

• lack ducts and therefore secrete into capillaries within the body: taken up in the blood → move through whole body

  • ex. many hormone producing glands such as the thyroid gland and adrenal glands

Exocrine and endocrine gland formation

1. epithelium and connective tissue

2. epithelial cord or tubule forms

3. it can either

   • exocrine gland

     • connecting cells persist to form duct

     • deepest cells become secretory

   • endocrine gland

     • cells from surface epithelium grow down into underlying tissue

     • deepest cells remain to secrete into capillaries

     • connecting cells disappear

Connective tissue

characterized by a matrix made up of protein fibers, extracellular material, and specialized cells

1. connective tissue proper

2. cartilage

3. bone

4. blood

connective tissue proper

• support and flexibility

• a lot of diseases arise from this

  types

  • loose connective

  • dense regular connective

  • adipose tissue

  • dense irregular

loose connective

space for blood vessels and nerves (support and flexibility)

ex. dermis of skin (middle layer)

dense regular connective

• not as much space, organized, very minimal ground substance

• strong and resistant to stretching

• organized one way → can only resist in one direction

ex. tendons and bones

Adipose tissue

stores fat

• protect organs, thermoregulation

dense irregular connective tissue

composed of densely packed collagen fibers in various arrangements to resist force

• strength and flex

• visceral organs

Cartilage

• composed of cells called chondrocytes surrounded by a semi solid ground substance

  • flexy and supportive but different

• serves as a template skeleton during bone development

• found in joint to provide a gliding surface for bones

  • reduce friction

ex. cushion for ears, nose, and ribcage

Bone

dynamic and STRENGTH AND SUPPORT

a. cells called osteoblasts trap mineral salts, forming concentric layers of calcified material around a canal (central) filled with blood vessels and nerves

b. once the matrix has hardened, the cells are called osteocytes and live in spaces called lacunae

• trap inside mineral salts

c. the dentin of a tooth is similar to bone and is made by cells in the pulp; the outer enamel is harder than bone or dentin

Organ

composed of two or more tissues that serve different functions in the organ (overall specific function)

largest organ in the body

skin: has all four primary tissues

• epidermis: keratinized stratified squamous epithelium to protect against water loss and abrasion (protective layer)

• dermis: dense irregular connective tissue containing exocrine glands, hair follicles, sense receptors, and blood vessels (all 4)

• hypodermis: adipose tissue for padding and insulation (subcutanious level)

• errector philli: arm hair up

Types of Stem Cells

totipotent: cells can become any type of cell; true stem cells (make whole organism and supporting structures)

• ex. zygotes

• as cells being to differentiate, a few adult stem cells are retained to allow for cell replacement

multipotent: limited to narrow range of possibilities but can become several related cells

• ex. adult stem cells

pluripotent: can form any type of unrelated cells (can make the body but not the extra-embryonic stuff)

organ systems

• integumentary: protection, thermoregulation

• nervous: regulation of other body systems

• endocrine: secretion of regulatory molecules called hormones

• skeletal: movement and support

• muscular: movements of the skeleton

• circulatory: movement of blood and lymph

• immune: defense of the body against invading pathogens

• respiratory: gas exchange

• urinary: regulation of blood volume and composition

• alimentary: breakdown of food into molecules that enter the body

• reproductive: continuation of the human species

Body Fluid Compartments

Intracellular: area inside the cell, 65% of total body water

Extracellular: outside the cell, blood plasma and interstitial fluid

both primarily filled with water and are separated by membranes

selective movement of molecules and ions between compartments through the cell membrane

In blood, what two molecules stabalize pH?

bicarbonate ion (HCO3-) and carbonic acid (H2CO3)

if blood falls below pH 7.35, the condition is called

acidosis

If the blood rises above pH 7.45, the condition is called

alkalosis

Micelles and Water

keep lungs from collapsing

• surfactants: lubricant to reduce water friction

Cholesterol

a steroid that is a per cursor for a lot of steroid hormones and other functional groups within the body

Prostaglandins

type of fatty acid with a cyclic hydrocarbon group

• regulate the diameter of blood vessels

• uterine contractions

Phosphatases vs. Kinases

Phosphatases: remove phosphate group

Kinases: add phosphate group

Isoenzymes

an enzyme that does the same job in two different organs has the same name, molecules may be slightly different

• useful in detecting and diagnosing certain diseases

Are most metabolic pathways branched or unbranched

branched

how do we mediate our bodies

through END PRODUCT INHIBITION

• the effect of the production of an end product or an intermediate in between allows us to shift to a new pathway

Inborn errors of metabolism

Abnormal gene makes defective enzyme (Enz3)

• can no longer have access to that pathway

• causes the build up of other enzymes

Example of Amino Acid Metabolism defect

Phenylketonuria (PKU)

• increase in phenylpyruvic acid,

• mental retardation, epilepsy

• cant drink diet coke

Different organs rely on different molecules to supply main energy source

• brain → mainly glucose

• resting skeletal muscle → fatty acids

• Liver → fatty acids

• Heart → fatty acids

Glucose sparing

organs will restrict their use of glucose to maintain blood glucose levels for use by the brain

Extracellular Environment

includes everything located outside of the cell

• cells receive nourishment from and release wastes into extracellular environment

• cells (facilitate) communication with each other by secreting chemical regulators (hormones, neurotransmitters)

maintain cellular function and release waste

Extracellular environment percentages

67% of the bodies water is within the intracellular compartment of cells

the rest of the 33% which is extracellular fluid is broken down into

• 80% interstitial fluid (bridge between inter and blood plasma)

• 20% blood plasma (exchange and waste

Extracellular Matrix ECM

• composed of protein fibers such as collagen and elastin: provide structural support

• a gel like ground substance made of glycoproteins and proteoglycans

Integrins

a type of glycoprotein within the extracellular matrix that connects the cells cytoskeleton to the ECM

• cell adhesion and mobility

• relay signals between extracellular and intracellular

• establish cell polarity

• communication and coordination

Plasma Membrane permeability

selectively permeable

• generally not permeable to proteins, nucleic acids, or other large molecules; big large polymers cannot

  • glucose is permeable with help from proteins, starch is not

• generally permeable to wastes and nutrients

• some ions are transported creating electrochemical currents in certain cells

Carrier: mediated transport

integral protein within the membrane

• facilitated diffusion: no energy, just need correct protein (passive)

• active transport: needs energy

Non carrier mediated transport

• simple diffusion of lipid soluble molecules (steroid hormones)

• simple diffusion of ions through nonspecific channels (calcium)

• simple diffusion of water (osmosis) through AQUAPORIN channels

  • allows for movement of water through membrane

Passive Transport

molecules move from higher to lower concentration without using metabolic energy

active transport

molecules move from lower to high concentration using ATP and specific carrier pumps

Types of Passive Transport

1. simple diffusion of lipid soluble molecules (nonpolar) through the phospholipid bilayer of the plasma membrane

2. Simple diffusion of ions (dissolved in water) through membrane channel proteins (due to their charge)

3. facilitated diffusion of glucose or other small organic molecules: bind to a specifc carrier protein which undergoes a conformational change to release the molecule on the other side of the membrane

how will diffusion occur?

without a physical separation or across a permeable membrane

net diffusion

due to random movement, the net direction of diffusion is from high to low solute concentration

Mean diffusion time

the average time it takes for a solute to diffuse (varies)

a. increases with the square of the distance the solute must travel (less distance, faster)

B. distance beyond 100 um, diffusion time is too long to be effective

diffusion through a dialysis membrane

• wont allow large proteins out

• some glucose

• starch cannot move in and out

• allows small diffusable molecules and ions out

Diffusion through the plasma membrane

• small, nonpolar, lipid-soluble molecules such as oxygen, carbon dioxide, and steroid hormones can easily pass through the lipid bilayer → GAS EXCHANGE

  • oxygen diffuses into cells while carbon dioxide diffuses out, driven by concentration gradients

  • in the lungs, these directions will reverse (o2 out, co2 in)

• water can not move freely through the membrane so it passes by through specialized channels called aquaporins → OSMOSIS

• these mechanisms are essential to maintaining cellular function and homeostasis

• also at the capillary beds

ions pass through membrane channels

charged ions can pass through ion channels that may be

• closed/gated: closed until certain needs are met

• open: free flowing

side note: large polar molecules can not pass through the membrane by simple diffusion but need special carrier proteins to passively cross if going with concentration gradient

rate of diffusion

measured by the number of diffusing particles per unit of time

depends on

• magnitude of concentration difference: driving force for diffusion (great difference→ rate faster, how fast?)

• permeability of the membrane to the molecules (increase permeability → rate increase)

• temperature of the solution: higher temperature increases the rate

• surface area of the membrane; increased by microvilli (in gastro tract)

osmosis

the movement of water molecules/ solvent through the plasma membrane

• greatly facilitated by protein channels called aquaporins → allow water to move efficiently

• aquaporins are abundant in tissues like the kidneys, eyes, lungs, salivary glands, and brain (precise water regulation is essential for functions)

when does osmosis occur

when there is a difference in solute concentration across a membrane that is permeable to water

• the membrane must be impermeable to the solute; otherwise the solute would move eliminated the concentration gradient

• solutes that cant cross the membrane but drive water movement are called osmotically active

• crucial for maintaining proper fluid balance in cells and tissues

the effects of osmosis

water moves from the side with more water (a more diluted solution) to the side with less water (less diluted)

• however we usually describe this in solute concentration

• water moves from areas with low solute concentration to area of high solute concentration

• water moves towards the side with more solutes to balance the concentration, a key process in maintaining cellular and physiological equilibrium

Osmotic pressure

the force needed to stop water movement during osmosis

• reflects the “pull” a solution has on water

  • solutions with higher solute concentrations have higher osmotic pressure, drawing in more water

  • pure water has osmotic level of zero, no solute

• essential for understanding how cells regulate water balance and maintain proper function in varying environements

Osmolality (not tested)

the total molality of a solution when you combine all the molecules within it

• amount of solute/ amount of solvent

hyposmotic and hypotonic

solutions with lower solute concentrations; water moves into the cell; causes cells to swell and eventually burst

• hemolysis in red blood cells

hyper osmotic and hypertonic

solutions with higher solute concentrations; water moves out of the cell; leads to shrinkage

• crenation in red blood cells

Tonicity importance

crucial in medical setting, like administering IV fluids, to ensure cells remain in a balanced, isotonic environment

Homeostasis of Plasma Concentration

when dehydration occurs, osmoreceptors in the hypothalamus detect increased plasma osmolality (more solute than solvent) → triggers a negative feedback loop to restore balance

1. Thirst increases, prompts water intake

2. hypothalamus signals the release of antidiuretic hormone (ADH) or vasopressin, from the posterior pituitary. ADH reduces water excretion by the kidneys which conserves water and concentrates urine

3. As plasma osmolality decreases back to normal, osmorecpetors are no longer stimulated, ADH release diminishes, and the kidneys excrete more water

System ensures fluid balance and protects cellular and neural functions

Carrier Mediated Transport

• movement of large, polar molecules requires membrane proteins (amino acids, glucose, and other organic compounds) due to size and charge

• rely on carrier proteins embedded into the plasma membrane to facilitate their transportation

  • highly specific carriers to particular molecules

• can be competition for similar carriers, and because the number of carriers is limited, the process can become saturated if too many molecules are trying to move at once → slows down transport

ALSO: some proteins can transport more than one molecule, but there is competition effect. Transport rates increase increased molecule concentration until saturation is met; this is the transport maximum (Tm) where all carriers are in use

Facilitated diffusion of glucose

• relies on the random movement of molecules and does not require ATP

• moves substances from areas of high to low concentration (follow gradient)

• requires specific carrier proteins in the plasma membrane ex. those used to transport glucose into a cell

• transport proteins can either 1. always be present in the membrane or 2. be inserted when needed depending on cell requirements

Glucose: carrier proteins like GLUT transporters help move glucose into cells, ensure it is available for energy production without expending cellular energy

Gluts

• Glucose Transporter Proteins

• maintain some at all times

• 14 known gluts

  • structural similarities are categorized together

• Gluts 1, 3-5, and 8 are found in the CNS (3-5 are in the prefrontal cortex for working memory)

• Glut 14 is only in the male testes

Active Transport Pump

used to move molecules from low concentration to high concentration, “moving uphill”

• requires the expenditure of ATP (uses ATP/energy)

• Carrier-mediated proteins that facilitate this kind of movement are known as PUMPS

Primary Active Transport

where hydrolysis of ATP directly power the transport process; the tranport protein itself acts as an ATPase enzyme, breaking down ATP to release energy; when ATP is hydrolyzed, the pump becomes activated through phosphorylation

ex. Ca2+ pump: found within the endoplasmic rectilium of striated muscle cells

• pump moves calcium ions out of the cytoplasm either in the extracellular or the cisternae of the ER

• This action creates a strong concentration gradient, enabling rapid movement of Ca2+ back into the cell when needed

• Plays a crucial role in processes such as neurotransmitter release in neurons and muscle contractions, ensuring proper cellular function and response to stimuli

Na/ K Pump

essential for maintaining proper cellular functions; found in all body cells

• it is an ATPase enzyme that actively transports sodium and potassium ions aganist their concentration gradient

• pumps 3 Na out and 2 K out of the cell, crucial for several cellular functions/ maintains that intracellular negativity (3 Nathans out, 2 Katies in)

Na/ K pump functions

1. provides energy for coupled transport, helping other molecules move across the membrane

2. generates electrochemical impulses in neurons and muscle cells, allowing for nerve signaling and muscle contractions

3. helps maintain proper osmolality within cells, ensuring water balance

Na/ K Pump steps

1. three Na ions from the cytoplasm bind to the pump

2. the atpase enzyme activates, hydrolyzing ATP to ADP and Pi, causing both openings of the pump to be blocked

3. ADP is released → causes a change that allows 3 Na ions to exit the pump into the outside of the cell

4. Two K ions then enter the pump from the outside and the Pi is released

5. the pump returns to its original shape and releases the 2 K ions inside the cell

this process is critical for maintaining cell volume, membrane potential, and proper function across a wide range of tissues

transport across epithelial membrane

key role in processes like absorption and reabsorption

• absorption: refers to the movement of digestive products, such as nutrients, across the intestinal epithelium into the blood stream

• reabsorption: the process by which molecules are transported from the urinary filtrate back into the blood

Epitheila Membrane Transport Two Pathways

1. Transcellular transport: molecules move through the cytoplasm of epithelial cells

2. Paracellular transport: molecules move through tiny gaps between epithelial cells, however this movement is limited by junctional complexes which regulate permeability

Junctional Complexes

1. Zonula occludens (tight junctions): these prevent easy diffusion between cells, keeps it tight ;)

2. Zonula adherens: help to anchor cells together and maintain tissues integrity

• same for macula adherens (desmosomes)

Transport across these membranes often require specialized carrier proteins (Na/K pump or the Na/H pump) which are located at the both apical and basolateral sides of the epithelial cells

• facilitate the movement of molecules in and out of the cells

• ensures that esstential substances are absorbed and waste products discared and nutrients are reabsorbed effectively

Exocytosis

the process by which large molecules, like proteins, hormones, and neurotransmitters are secreted by the cell

• involves the fusion of a vesicle with the plasma membrane allowing the contents to be released outside the cell

• this requires energy in the form of ATP to fuel the vesicles movement and fusion with the membrane

endocytosis

how large molecules, such as cholesterol, are brought into the cell

• often involves receptor mediated endocytosis: specific transport proteins on the plasma membrane interact with molecules outside the cell, which triggers the formation of a vesicle that engulfs the target molecule

• uses ATP

both endo and exo are crucial for maintaining cellular communication and function, enabling cells to secrete necessary substances or take in essential molecules

Chemical Signals for Cell Communication: each serves a specific purpose in regulating physiological processes

1. Gap junctions: allows adjacent cells to pass ions and regulatory molecules through channels between them, facilitating direct communication for coordinated cell activity (not the same as tight junctions)

2. Autocrine signaling: occurs when a cell releases a chemical signal that acts on itself, influencing its own function or behavior

3. Paracrine signaling (local): cells within the same organ releasing signaling molecules into the extracellular space, which then diffuse to nearby target cells; often referred “local” because the signals affect only nearby cells

4. Synaptic signaling: is unique to the nervous system; neurons release neurotransmitters across synapses to communicate with target cells, such as other neurons, muscles, or glands, enabling fast and precise control of body functions

5. Endocrine signaling: carried out by glands that secrete hormones directly into the bloodstream, hormones can travel long distances to target cells in various organs, allows the body to regulate broader processes, such as growth, metabolism, and reproduction

Each of these signaling methods plays a crucial role in maintaining homeostasis and coordinating complex biological systems

How regulatory molecules affect their target cells

Recpetor proteins are crucial for cellular communication, allowing target cells to respond to specific signals

• A target cell can receive a signal because it has receptor proteins either on it plasma membrane or inside of the cell, each is specific to the signal molecule

Nonpolar signal molecules

such as steroid hormones, thyroid hormones, and nitric oxide gas can easily pass through the plasma membrane due to the lipid soluble nature

• once inside, they bind to intracellular receptors and initiate a response, often influencing gene expression

large polar signal molecule

like epinephrine, acetylcholine, and insulin cannot pass through the plasma membrane due to their size and charge

• instead, they bind to receptors on the cell surface

• these interactions trigger a cascade of intracellular signaling events through SECOND MESSENGERS

• these second messengers may include ions like calcium or small molecules, carry the signal inside the cell and mediate various changes, such as altering enzyme activity or gene expression, enabling the cell to respond to the external signal

G protein cycle

Second messengers are crucial for transmitting signals inside cells, and one of the most common second messengers is cycle adenosine monophosphate (cAMP)

• the process begins when a signaling molecule, such as a hormone or neurotransmitter, binds to a receptor on the cells surface

• the binding activates an enzyme that catalyzes the conversion of ATP into cAMP

• once cAMP is produced, it activates other enzymes in the cytoplasm, which triggers a variety of cellular responses and changes in cell activity, such as altering metabolism or gene expression

However, the receptor proteins that bind the signal and the enzyme proetins that produce the second messenger are rarely directly connected

• they rely on G-proteins to shuttle the signal between them

• G proteins are made up of three subunits; alpha, beta, and gamma

• When the signaling molecule binds to the receptor, the alpha subunt dissociates from the comples and moves to the enzyme or ion channel, initiating the production of cAMP or other signaling events

this ensure that the signal is efficiently transmitted and amplified within the cell

introduction to physiology

the stud of biological functions; how the body works

1. normal functions of cells to organisms as a whole

2. mechanisms

3. cause and effect sequence

4. scientific experiments derived

Pathophysiology

a disruption of normal function

• how disease or injury affects physiological processes

  • outlyers

  • why is it different

• aids understanding of normal processes

Comparative physiology

• studies the differences and similarities in the function of invertebrates and vertebrates

• aided in the development of pharmaceutical drugs

Scientific Method

1. observations

2. hypothesize

3. design and conduct

4. analyze

5. results replication

6. present

Good Physiological Research Requires:

to ensure accuracy

1. quantifiable measurements

2. an experimental group and control group

• independent and dependent variables

• extraneous/ cofounding variables: miss alignment in the data we can not control

  • ex. biological sex, chronological age (ethically can not change)

3. reduction of biases

4. statistical analysis: qualifiers may help (ozempic); determine significance

5. goal: review and publication by peer reviewed journal

Developing Pharmaceuticals

a. basic research is conducted for years before a drug is ever given to a person

b. research begins by studying the effects of a chemical on cells in vitro (in a culture dish)

c. next, studies are performed on animals (usually rats and mice) to see if the same effects occur in vivo and if there are any toxic side effects

• for these trials, many rats and mice are genetically modified to be susceptible to particular diseases, may take several years

d. clinal trials

Phases of Clinical trials

Phase 1: test drug on healthy human (no outlyers and normal physiology) volunteers to test for side effects, rates of passage, dosage, etc.

Phase 2: test effectiveness on people with the particular disease (ideal are otherwise healthy)

Phase 3: large number of people including both sexes, many age groups and ethnicities and people with more than one health condition (extraneous variable testing)

• From here the FDA can approve

Phase IV: test other applications for the drug

ex. viagra: initially blood pressure medication, goes through phase 4 and now works for erections

It is possible to go backwards and retest certain phases

Claude Bernard

observed that the internal environment stays relatively constant although changes are occuring

Walter Cannon

coined the term homeostasis to describe the internal consistency of the body

Homeostatsis

constancy of the internal environment

• main purpose of our physiological mechanisms is to maintain

• deviation from homeostasis → disease (sustained deviation)

• accomplished mostly by negative feedback loops (95%)

Pavlov and Crick Watson Franklin and Wilkins

Pavlov: digestion

Crick, Watson, Franklin, and Wilkins: structure of dna

Negative Feedback Loops

Pathway

1. Stimulus: never stops, changes within the environment

2. receptors, which act as sensors in the body to detect change and send information to the:

3. Integrating center, which assesses change around a set point, then sends instructions to:

4. Effector (muscle or glands) which can make the appropriate adjustments to counter the change from the set point

Mechanism of Negative Feedback Loops

a. moves in the opposite direction from the change

b. makes the change from the set point smaller

c. reverse the change in the set point

d. continuous process, always making fine adjustments to stay in homeostatsis

set point =

dynamic consistency (range of setpoints)

If effectors continuously run, what will occur

disease

antagonistic effectors

oppsoing effectors that move conditions in opposite direction

• maintains conditions within a certain normal range, or dynamic consistency

• when you are hot you sweat, when you are cold you shiver

• ex. blood glucose levels, blood calcium levels, heart rate, and blood pH

Quantitative measurements

• to study physiological mechanisms, scientist must measure specific values and mathematically determine such statistics as their normal range, their averages, and their deviations from the average (set point)

• knowledge of normal ranges aid in diagnoses of disease and in assessing the effects of drugs and other treatments

Normal range of 

• Arterial pH

• Glucose

• 7.35 to 7.45

• 70 - 99 mg/100ml

Positive Feedback

the end product in a process stimulates the process

• the action amplifies the changes that stimulate the effectors → completion

• positive feedback can not work alone, but it does contribute to many negative feedback loops

ex. blood vessel if damaged, a process begins to form a clot (pos fed), once damage is fixed clotting ends (neg fed)

the strength of uterine contractions during childbirth is also a pos fed

Regulation of Processes within Organs

Intrinsically: cells within the organ sense a change and signal to neighboring cells to respond → changes function periodically in organ ex. clotting

Extrinsically: the brain or other organs, regulate an organ using the endocrine or nervous system

• the endocrine releases hormones into the blood which transport to target organ

• nervous system “innervates” organs with nerve fibers

Negative Feedback Inhibition

a closed loop control system that usually involves an antagonist to make sure homeostasis is maintained within normal levels

ex. when blood sugar is low, the hormone glucagon (antagonist) is secreted with increases blood sugar

Levels of organization

1. cell

2. tissue

3. organ

4. system

5. organism