1. To excrete waste products of metabolism:

   1. urea, metabolite of protein

   2. uric acid, metabolite of nucleic acid (uric acid, for ex., would be increased in leukemia patients).

2. To regulate concentration of water and electrolytes in our body:

   1. Na+, Cl-, both of which are controlled by our old friend renin-angiotensin system and blood volume

   2. Water, controlled mainly by ADH

   3. K+, regulated by secretion of aldosterone, and by acid/base balance.

   4. Ca2+, PO4(3-), regulated by Vitamin D. (the 1^st hydroxylation of Vit D occurs in the liver (hydroxylation of carbon 1). 2^nd hydroxylation is in the kidney. This hydroxylated vit D from the liver can actually be activated in the kidney (1, 25 colecalciferol) or inactivated in the kidney (24, 25 colecalciferol)

3. To maintain acid/base balance:

   1. secretion of H+

   2. reabsorption of HCO3-

4. Endocrine functions:

   1. production of erythropoietin, which regulates rbc mass. Obviously, with chronic renal failure and decreased production, the person can become anemic.

   2. renin, secreted by juxtaglomerular cells in afferent arteriole, reacts to any changes of blood pressure (or Na concentration)

Nephron is the functional unit of the kidney, composed of the glomerulus and the tubules (PCT, loop on Henle, DCT, collecting tubule). Urine, which is the filtrate of plasma, flows from the collecting tubule into the collecting duct. From there it goes to the minor calyx, major calyx, and out into the pelvis of the kidney. Then it’s on it’s away to the ureter, bladder, and finally out of the urethra.

Kidney has a capsule on the outside, and it is surrounded by fat. Hilus of the kidney contains renal artery, veins, and major calyces (or the collection of those, called renal pelvis)

Kidney is anatomically divided into:

1. Cortex, which contains mostly glomeruli

2. Medulla, which contains mostly loops of Henle, collecting ducts

A little about renal vasculature:

Renal a. enters the hilus of the kidney and splits into anterior and posterior renal a. Those further divide into interlobar a. (go between the pyramids), which divide into arcuate a. (go between the cortex and the medulla), which divide into interlobular a., which divide into afferent arterioles, which enter into glomerulus (capillaries), and leave as efferent arterioles (the portal system) and become peritubular vasa recta (capillaries), which go down the loop of Henle, then become venules, and eventually coalesce to become the renal vein and come out of the hilus.

Cerebral oedema. In high mountainous areas one should watch out for acute cerebral oedema due to altitude sickness in cases of acute confusion, Cheyne-Stokes respiration, ataxia, disorientation or other neurological problems. Fast administration of oxygen and dexamethasone and immediate evacuation to an area at lower altitude with medical infrastructure is imperative. Acetazolamide (Diamox®) can be used prophylactically with limited efficacy.

It should of course be borne in mind that an already existing cardiovascular disease can worsen the relative hypoxia at high altitude.

A poorly burning stove in an unventilated environment can cause carbon monoxide poisoning (CO-intoxication).

Mefloquine taken for malaria prevention in low-lying areas and continued to be taken in the mountains can result in confusion. The same warning applies for alcohol.

• An ideal antiarrhythmic drug should target ectopic pacemakers and rapidly depolarizing tissue to a greater extent than normal tissues of the heart

• Many of the sodium (Class I) and calcium (Class IV) channel blockers have this property because they preferentially block sodium and calcium channels in depolarized tissues

• Enhanced sodium or calcium channel blockade in rapidly depolarizing tissue has been termed "use-dependent blockade" and is thought to be responsible for increased efficacy in slowing and converting tachycardias with minimal effects on tissues depolarizing at normal (sinus) rates

• Many of the drugs that prolong repolarization (Class III drugs, potassium channel blockers) exhibit negative or reverse rate-dependence

  • These drugs have little effect on prolonging repolarization in rapidly depolarizing tissue

  • These drugs can cause prolongation of repolarization in slowly depolarizing tissue or following a long compensatory pause, leading to repolarization disturbances and torsades de pointes

Modulated Receptor Theory (MRT)

• A theory to explain use-dependent blockade, termed the modulated receptor theory (MRT), has been proposed and used to explain many characteristics of the sodium channel blockers and calcium channel blockers

• The theory is based on a three-state model for the sodium channel originally proposed by Hodgkin and Huxley:

  • The three normal channel states are: Resting, Open (or Activated), and Inactive

    • Under normal resting (polarized) conditions, the sodium channels are predominantly in the Resting state and are nonconducting

    • When the membrane is depolarized, the sodium channels Open and conduct sodium, resulting in the inward sodium current that makes the major contribution to phase 0 of the action potential

    • The inward sodium current rapidly decays as channels move to the Inactive state

    • The return of the Inactive channel to the Resting state is termed reactivation and is voltage- and time-dependent.

  • The theory assumes that channel blocker drugs bind different channel states with different affinities and that drug binding alters the transition rates between different states

  • Drug binding results in transitions to R*, O*, and I* , channel states which have different transition rates between states than the normal channel states

  • The most clinically useful drugs would have affinity for the Open and/or Inactive state, and thereby exhibit use-dependent blockade

  • Drugs with high affinity for the Resting state would be toxic

  • Additive and synergistic interactions between drugs that prolong action potential duration and those that have high affinity for the Inactive state have been predicted (e.g.- lidocaine and quinidine); combination therapy in experimental settings using low doses of each drug has indicated greater efficacy and fewer side effects than high doses of the individual drugs

Guarded Receptor Theory

• An alternative theory for channel blockers is termed the "guarded receptor" model and it assumes that drug binding to different channel states is regulated by access or egress of drug to drug binding sites on the channel

• This theory may be more useful in analyzing the properties of ionizable channel blockers whose access to the intracellular drug-binding sites is pH-dependent

• Other potentially useful models to predict the actions of channel blockers are based on the size, pK, and solubility of drugs

Examples of Channel Blockers Showing Use-Dependent Blockade

• Quinidine, procainamide, and disopyramide preferentially bind to the Active state of the sodium channel

• Amiodarone binds almost exclusively to the Inactive state of the sodium channel

• Lidocaine binds Active and Inactive states of the sodium channel

• Verapamil and diltiazem bind Active and Inactive states of the calcium channel

• Quinidine, bretylium, and sotalol show reverse use-dependence towards potassium channel blockade

• All this cell can do is note concentration of Chloride

  • Stimulates the JG cells

    • Juxtaglomerular cells

      • They release renin, which is a hormone,

      • And is released straight into the blood pool (vascular tree)

      • Renin acts as a cleaver…it is looking for angiotensinogen (precurser molecule found in the liver) it is going to cleave off a part of the structure to reveal a binding site

        • Now it is called angiotensin 1 - Now it is carried to the Lung

        • Here it meets ACE - Angiotensin Converting Enzyme. Now another binding site is exposed and it is now called angiotensin II (Angiotensin 1 + ACE = Angiotensin II)

          • It is the strongest thing we know for the elevation of aldosterone (targets sodium & is recoverd more from the urine)

            • Reduction of Na+ loss and pulls the water with it. Increases the vascular volume increasing the BP in the body

          • Increase the hydrostatic pressure in the glomerulus (turns up the leak hose, & increase GFR)

• Vestibular apparatus maintains the body (mainly the head) at equilibrium (at balance) and stabilizing the eyes relative to the environment

• Static equilibrium- maintenance of the position of the body (mainly the head) relative to the force of gravity

• Dynamic equilibrium- maintenance of the position of the body (mainly the head) in response to sudden movements such as rotation, acceleration, and deceleration.

• Consists of 2 parts:

• Otolithic organs

• Utricle and saccule- static equilibrium

• Semicircular canals- dynamic equilibrium

• Bony labyrinth surrounds membranous labyrinth filled with endolymph (like ECF).

• Between bony labyrinth and membrane of membranous labyrinth is perilymph (like CSF)

Otolithic organs

• Utricle and saccule

• Saccule connected to utricle by duct.

• Each sensory area consist of a macule that contains the sensory mechanisms

Utricle

• an irregular, oblong membranous sac located on the medial wall of the vestibule.

• lies horizontally

• More sensitive to horizontal acceleration.

• macula consist of sensory hair cells and supporting cells (sustentacular cells)

• Each sensory hair cell has one kinocilium and many stereocilia

• The stereocilia and kinocilium are embedded in a gelatinous membrane, the otolithic membrane, which sits on top of the sensory cells.

• The membrane is produced by the sustentacular cells.

• On the surface of the otolithic membrane are otoliths (or otoconia), crystals of Ca⁺⁺ carbonate which are composed of calcium carbonate and protein.

• These otoliths sensitive to horizontal movements

Saccule

• a flattened, irregularly-shaped membranous sac also located in the medial wall of the bony vestibule.

• saccular macula, having the same struture as the utricle, lies perpendicular and verticle to the macula of the utricle.

• More sensitive to vertical (saggital plane, up and down forward and back) acceleration.

• has two small openings are present in the saccule.

• One is the opening of a duct, called the endolymphatic duct, that communicates with the utricle.

• The other opening communicates with the duct of the cochlea via the ductus reuniens.

Semicircular Canals

• Provide information about rotational acceleration.

• Project in 3 different planes.

• Each canal contains a semicircular duct. At the base is the crista ampullaris.

• = enlarged swellings at base of each canal communicating with utricles

Endolymph Movement in Canals

Movement of Cupula Relative to Body Movement

• Eyes transduce energy in the electromagnetic spectrum into APs.

• Only wavelengths of 400 – 700 nm constitute visible light.

• Neurons in the retina contribute fibers that are gathered together at the optic disc, where they exit as the optic nerve.

Refraction

• Light that passes from a medium of one density into a medium of another density (bent).

• Refractive index (degree of refraction) depends upon:

• Comparative density of the 2 media.

• Curvature of interface between the 2 media.

• Refractive index of air = 1.00

• Refractive index of cornea = 1.38

• Image is inverted on retina.

Accommodation

• Ability of the eyes to keep the image focused on the retina as the distance between the eyes and object varies.

Changes in the Lens Shape

• Ciliary muscle can vary its aperture.

• Distance > 20 feet:

• Relaxation places tension on the suspensory ligament.

• Pulls lens taut.

• Lens is least convex.

• Distance decreases:

• Ciliary muscles contract.

• Reduces tension on suspensory ligament.

• Lens becomes more rounded and more convex.

• Pressure (blood pressure)

  • Hydrostatic pressure

  • Osmotic pressure

  • High enough to leak, but low enough to let is go

  • Pressure must be low enough to receive the pressure from the bowman's capsule

• Dehydration

  • Higher osmotic pressure - resist fluid out flow

• Hypertensive

  • Increased GFR

    • Higher pressure

    • Proteins then can leak out

• Stone @ base of bladder

  • Cause a back up al the way to the bowman's capsule

  • Decrease GFR

  • Increased serum levels of urea

    • Obstruct the system (reduce GFR) - cannot get rid of it

      • Alternate input sites are full already

    • Dehydration

• Parathormone

  • Control bone maturation and bone growth

  • Any time the pt. System sees a decline in Ca+ - Parathormone will be released

    • Weakens the bonds of the crystal lattice to help with the osteoclasts

• ADH

  • Anti-diuretic hormone

  • Not getting enough water or they are excreting too much

  • Diuresis

  • Clinical Dehydration will cauwse this to be present

• Aldosterone

  • When this elevates Na+ absorbed more in the DCT.

  • Na+ removed from the DCT this pulls water with it.

• Erythropoeitin

  • Stimulates the marrow to create new RBC's

  • Chronic renal failure can cause anemia

    • This can cause more infection

  • This causes an anemia of under production

    • Decreased Reticulocyte count

• Renin

  • Know the RAA system

  • Elevates to preserve tubular flow rate***

    • It will do it even when it should not do it

• Angiotension system (REGULATION OF BLOOD PRESSURE)

  • RAA system - renin angiotension aldosterone system

• Filtering system

  • Waste removal

• Hematpoesis

• Fluid balance

  • 99.998% of the water can be covered if needed

  • Acid base balance

    • Acidosis - too much hydrogen (alkalosis is opposite)

  • Electrolyte balance

1. General Features
1. transepithelial transport - nutrients must pass across the epithelial lining of the small intestine
2. active transport - most nutrients must be transported across membrane using ATP of the cells
2. Carbohydrate Absorption
• facilitated diffusion - glucose and galactose (coupled with active transport of Na+)
• "carrier molecule" has binding sites for both sugar and Na+; relies on Na+ gradient
3. Protein (Amino Acid) Absorption
• facilitated diffusion - amino acids and small peptides (coupled with Na+ active transport)
• "carrier molecule" has binding sites for both amino acid and Na+; relies on Na+ gradient
• food allergies - absorption of proteins in infant gut causes early immune reaction
4. Lipid Absorption
• micelles - tiny balls of fats that result from bile salt emulsification and "lecithin"
• contain cholesterol and fat-soluble vitamins
• diffuse through lipid bilayer of membrane
• chylomicrons - micelles combined with associated proteins within the cell; enter the lacteals of the lymphatic system
5. Nucleic Acid Absorption
• pentoses, nitrogen bases, phosphates - absorbed by similar processes as sugars and amino acids
6. Vitamin Absorption
• fat soluble - Vitamins A, D, E, K are absorbed by epithelial cells along with lipid micelles
• OLESTRA - will carry fat soluble vitamins out in feces with it
• water soluble - Vitamins B & C absorbed by diffusion
• Vitamin B12 - large and electrically charged, must bind with "intrinsic factor" before being taken into the cell by endocytosis
7. Electrolyte Absorption
• Fe and Ca - primarily absorbed in small intestine
• ferritin - sequesters Fe in intestinal cells
• transferrin - transfers Fe into circulation when need is present (menstruation)
• Vitamin D - facilitates Ca absorption
• Na - exchanged for sugars and amino acids
• Cl - absorbed into cells and exchanged for HCO3-
• K - absorbed into cells due to osmotic gradients
8. Water Absorption
• small intestine - 95% of water absorbed by small intestine following transport of solutes
• large intestine - absorbs remaining water before moving the chyme on to the rectum
9. Malabsorption of Nutrients
• impairment of bile or pancreatic juice release
• infections of the intestinal mucosa
• gluten enteropathy - "gluten" protein in grains damages the mucosa of the intestines

1. Enzymatic Hydrolysis ("water" "breaking")
• hydrolysis - a water molecule is added between two "monomers" of a complex organic molecule in order break it down into its component parts
2. Carbohydrate Digestion
• monosaccharides - "monomers" such as glucose, fructose, and galactose
• disaccharides - sucrose (table sugar), lactose (milk sugar), and maltose (grain sugar)
• polysaccharides - starch (grains), glycogen (muscle)
• carbohydrate hydrolyzing enzymes
• salivary amylase - produces "oligosaccharides"
• pancreatic amylase - in small intestine
• intestinal enzymes - dextranase & glucoamylase (> 3 sugars), maltase, sucrase, and lactase
• lactose intolerance - decreased ability to digest lactose in the diet (use "lactase" supplements)
3. Protein Digestion
• amino acids - the "monomer" components of protein
• stomach - pepsinogen -----> pepsin (low pH)
• small intestine
• enzymes that cleave throughout the protein
• trypsinogen ---------------> trypsin
• chymotrypsinogen ------> chymotrypsin
• carboxypeptidase (carboxyl end of protein)
• aminopeptidase, dipeptidase (amino end)

4. Lipid (Fat) Digestion
• lipid structure - glycerol + 3 triglycerides
• lipases - enzymes that break down lipids
• bile salts - "emulsify" fats in 1 micron "micelles"

5. Nucleic Acid Digestion
• pancreatic nucleases - break down DNA and RNA

1. Bacterial Flora
1. digest remaining carbohydrates
2. responsible for producing gas (flatus)
3. synthesize complex B vitamins and vitamin K
2. Digestion and Absorption
1. reclaim most of the water
2. reclaim some of the electrolytes (Na+ and Cl-)
3. Motility of the Large Intestine
1. haustral contractions - slow acting segmental motion; moves chyme from one segment to next
2. mass movements - peristaltic waves that move food to the rectum during/after eating
• diverticula - herniation of the mucosa through the wall of the colon sigmoidd colon)
4. Defecation
1. defecation reflex - when feces (stool) enters rectum, spinal cord reflex is triggered
• internal sphincter (involuntary)
• external sphincter (voluntary)
2. Valsalva's maneuver - contraction of diaphragm and abdominal muscles to increase pressure for defecation
3. diarrhea - too much water in the stool
4. constipation - insufficient water or fiber

GH

Low: short stature, delayed puberty [Treatment: TRH]

High: acromegaly, gigantism [T: somatostatin, dopamine analogues]

PROLACTIN

High: galactorrhea [T: bromocriptine, like DOPAMINE]

ADH/AVP/vasopressin

Low: Central DI, from posterior pituitary problem

High: Nephrogenic DI, ADH V2 receptor bad

Symptoms: high urine output, high osmolarity, low blood volume

Hypophysectomy: won't be secreting ADH so won't reabsorb water so

urinate more

THYROID

Hyper: Grave's Disease, Ab activates TSH receptor, high levels of T3 and T4, low TSH from negative feedback of T3, weight loss, hunger, nervousness, sweat, heat intolerance, high BMR, HR, goiter. Can also be caused by high TRH and TSH levels. [T: PTU]

Hypo: AI destruction of thyroid, low T3 and T4, TSH can be high or low. Weight gain, cold intolerance, low BMR, lethargy, goiter. Can cause cretinism (retardation) in developing fetus. [T: TH replacement]

Hashimoto's: main cause of goiter, AI activity towards thyroid gland, high TSH, low T3, T4

ADRENAL CORTEX

High cortisol: hyperglycemia

Low cortisol: hypoglycemia

High aldosterone: High K secretion, hypokalemia, hypervolemia

Low aldosterone: Low K secretion, hyperkalemia, hypovolemia

High androgens: masculinization of females

Low androgens: loss of pubic hair and libido in females

Addison's Disease: primary adrenal cortex deficiency, all 3 hormones low, also get hyperpigmentation form high ACTH levels and relates MSH levels. [T: H replacement]

Secondary adrenalcortical insufficiency: Low CRH and low ACTH. All 3 hormones low. Mostly normal aldosterone. No hyperpigmentation

Cushing's syndrome: High cortisol causes low ACTH. Obesity. DEX test lowers ACTH

Cushing's disease: High cortisol and high ACTH from pituitary tumor. DEX test does nothing. Central obesity, buffalo hump, striae, hyperglycemia [T: metyrapone blocks cortisol synthesis]

Conn's disease: Primary hyperaldosteronism, via tumor

21-B-hydroxylase deficiency: No aldosterone, cortisol. Shunts to androgens, virilization of females. High ACTH levels. [T: H replacement]

17-A-hydroxylase deficiency: No androgens or cortisol, shunts to aldosterone. Lack of pubic hair and low libido in women, high BP

INSULIN

Diabetes Type I: destruction of pancreatic B cells. Hyperglycemia, FFA, ketoacids, polyurea, thirst

Diabetes Type II: obesity causes, insulin resistance

PTH

Primary hyperPTH: From PTH tumors, high PTH, high cAMP, high blood Ca, stones bones and groans

Secondary hyperPTH: Vitamin D deficiency, high PTH, high cAMP, low calcitriol, low 25(OH)D, low Ca, low phosphate. Lack of vitamin D can lead to RICKETS

HypoPTH: Low PTH, low cAMP, low Ca, high phosphate. [T: Calciotriol]

Chronic renal failure: No calcitriol produced, bone abnormalities, 25 (OH)D in liver normal

PTH peptide: low PTH, high cAMP, high Ca

1.Hearing

-Unlike other sensory systems, the central auditory pathways have bilateral representation of

sounds (sound from 1 ear reaches auditory cortex in both hemispheres).

-Pathway

-first neruons in spiral ganglion synapse in cochlear nucleus

-second neurons synapse bilaterally in superior olivary nuclei

-third neurons travel in the lateral lemniscus to synapse in the inferior colliculus

-fourth neurons then synapse in the medial geniculate nucleus

-the fibers then go to the transverse temporal gyrus of the cortex

-Conduction and nerve deafness

-Weber test (forehead)

-lateralizes to the affected ear with conduction deafness and to the unaffected

ear with nerve deafness

-Rinne test (mastoid process)

-distinguishes between better bone or air conduction of sound

2. Extraocular muscles

-Movements and innervation

-Medial Rectus – CN III – adduction (in)

-Superior Rectus – CN III – elevation (after abduction) (up)

-Inferior rectus – CN III – depression (after abduction) (down)

-Inferior oblique – CN III – elevation and adduction (up and in)

-Superior oblique – CN IV – depression and adduction (down and out)

-Lateral rectus – CN VI – abduction (out)

-Lesions

-CN III – eye turned down and out, ptosis, mydriasis

-CN IV – eye slightly up and in – diplopia going down stairs – tilting head away from the

affected side to correct the diplopia

-CN VI – eye deviates medially (abductor paralysis)

3. Chemical synapse, neurotransmitters, receptors, second messengers, effects

-Chemical synapse (BRS phys pg. 13-14)

-Presynaptic cell

-action potential – depolarization of presynaptic terminal – Ca2+ enters

presynaptic terminal – release of neurotransmitter into cleft

-Postsynaptic cell

-neurotransmitter binds to receptors causing a change in permeability to ion

-inhibitory neurotransmitters hyperpolarize – excitatory depolarize

-Receptor types (BRS phys pg.35-38)

-alpha 1 receptors – excitatory – epi and norepi – IP3 and increase intracellular Ca2+

-alpha 2 receptors – inhibatory – inhibit adenylate cyclase and decrease cAMP

-beta 1 receptors – excitatory – epi and norepi – activate adenylate cylcase – cAMP

-beta 2 receptors – relaxation – epi and norepi – activate adenylate cyclase – cAMP

4. Blood supply to brain

-Embolism – most frequently to middle cerebral artery leading to contralateral paralysis,

motor defects, sensory defects, aphasias

-Thrombosis – from atherosclerosis of carotids, vertebral and basilar aa., and middle cerebral aa.

-Hemorrhage – hypertension and coagulation disorders – most often in basal ganglia, pons,

frontal lobe, cerebellum

5. Basal Ganglia (globus pallidus, caudate, putamen)

-initiation of voluntary movements and control of postural adjustments

-Pathology of the basal ganglia

-Negative signs: akinesia, bradydinesia, abnormal postural adjustments

-Positive signs (dyskinesia at rest): hypertonicity (rigidity), tremors, chorea, athetosis,

ballismus

-Huntington disease – degeneration of striatal neurons (putamen and caudate)

-Parkinson disease – degeneration of the dopamine neurons in the substantia nigra

-Tardive dyskinesia – exposure to manganese and drugs – hypersensitivity to dopamine agonists

-Hemiballismus – lesions in contralateral subthalamic nucleus

6. Pituitary associations

-Optic chiasm sits on top of pituitary – bilateral hemianopsia

-Sits in the sella turcica - local pressure effects hypopatuitarism

7.Brain MRI and CT

-Abcess or cysticercosis CT and MRI – ring enhancing lesion

-Multiple sclerosis MRI – multiple focal areas of demyelination (plaques) in brain and spinal cord

-Huntington’s disease – atrophy of the caudate nucleus, putamen, and frontal cortex – looks like

ventricles have enlarged

8. Pupillary light reflex - doesn’t involve cortex

-Direct response – afferent pathway is optic nerve of eye tested – efferent pathway is CN III

to the eye tested

-Consensual response – afferent pathway is optic nerve of eye tested – efferent pathway is

CN III of opposite eye

-Accomodation – pupils constrict, eyes converge, lense more convex – depends on CN III

and visual association cortex

1. Relationships of Pressure
• atmospheric air pressure - 760 mm Hg (at sea level)
• negative air pressure - LESS than 760 mm Hg
• positive air pressure - MORE than 760 mm Hg
• intrapleural pressure - pressure within the pleural "balloon" which surrounds the lung
• intrapulmonary pressure - pressure within the alveoli (tiny sacs) of the lung itself
2. Factors holding lungs AGAINST the thorax wall:
• Surface tension holding the "visceral" and "parietal" pleura together
• Intrapulmonary pressure ALWAYS slightly greater than intrapleural pressure by 4 mm Hg
• Atmospheric pressure acting on the lungs
• atelectasis (collapsed lung) - hole in pleural "balloon" causes equalization of pressure and collapse of the lung
• pneumothorax - abnormal air in the intrapleural space, can lead to collapsed lung
  

3. Factors facilitating lung movement AWAY from thorax wall:
• Elasticity of lungs allows them to assume smallest shape for given pressure conditions
• Fluid film on alveoli allows them to assume smallest shape for given pressure conditions

1. Boyle's Law on Volume/Pressure Relationships
1. Volume is INVERSELY proportional to Pressure
• INCREASE in Volume -> DECREASE in Pressure
• DECREASE in Volume -> INCREASE in Pressure
• VOLUME change --> PRESSURE change----> gas flows to equalize the pressure
2. 2. Simple Example of Boyle's Law
• - plastic bag with plastic tube in the top
• - as bag expands by pulling, gas moves IN
• - as bag shrinks by squashing, gas moves OUT
2. Inspiration
1. diaphragm muscle contracts, increasing thoracic cavity size in the superior-inferior dimension
2. external intercostal muscles contract, expanding lateral & anterior-posterior dimension
3. INCREASED volume (about O.5 liter) -----> DECREASED pulmonary pressure (-1 mm Hg) -----> air rushes into lungs to fill alveoli
4. deep/forced inspirations - as during exercise and pulmonary disease
• scalenes, sternocleidomastoid, pectorals are used for more volume expansion of thorax
3. Expiration
1. quiet expiration (exhalation) - simple elasticity of the lungs DECREASES volume -----> INCREASED pulmonary pressure -> movement of air out of the lungs
2. forced expiration - contraction of abdominal wall muscles (ie. obliques & transversus abdominus) further DECREASES volume beyond relaxed point ----> further INCREASE in pulmonary pressure -----> more air moves out

1. Respiratory Passageway Resistance
1. upper respiratory passageways - relatively large, very little resistance to airflow (unless obstruction such as from food lodging or cancer)
2. lower respiratory passageways - from medium-sized bronchioles on down, can alter diameter based on autonomic stimulation
• a. parasympathetic - causes bronchioconstriction
• b. sympathetic - inhibits bronchioconstriction
• epinephrine - used to treat life-threatening bronchioconstriction such as during asthma and anaphylactic shock (carried by people susceptible to sudden constriction)
2. Lung Compliance & Elasticity
1. Lung Compliance - the ease with which lungs can be expanded by muscle contraction of thorax
• fibrosis - decreases compliance
• blocked bronchi - decreases compliance
• surface tension - alveoli difficult to expand
• thorax inflexibility - decreases compliance
2. Lung Elasticity - the ease with which lungs can contract to their normal resting size (exhalation)
• emphysema - decreases elasticity
3. Alveolar Surface Tension - liquid on surface of alveoli causes them to collapse to smallest size
• surfactant - lipoproteins that reduces surface tension on alveoli, allowing them to expand more easily
• infant respiratory distress syndrome - premature babies that do not yet produce enough surfactant; must be ventilated for respiration

1. Respiratory VOLUMES (20 yr old healthy male, 155 lbs.)
1. tidal volume (TV) - normal volume moving in/out (0.5 L)
2. inspiratory reserve volume (IRV) - volume inhaled AFTER normal tidal volume when asked to take deepest possible breath (2.1-3.2 L)
3. expiratory reserve volume (ERV) - volume exhaled AFTER normal tidal volume when asked to force out all air possible (1.0-2.0 L)
4. residual volume (RV) - air that remains in lungs even after totally forced exhalation (1.2 L)
2. Respiratory CAPACITIES
1. inspiratory capacity (IC) = TV + IRV (MAXIMUM volume of air that can be inhaled)
2. functional residual capacity (FRC) = ERV + RV (all non-tidal volume expiration)
3. vital capacity (VC) = TV + IRV + ERV (TOTAL volume of air that can be moved)
4. total lung capacity (TLC) = TV + IRV + ERV + RV (the SUM of all volumes; about 6.0 L)
3. Dead Space
1. anatomical dead space - all areas where gas exchange does not occur (all but alveoli)
2. alveolar dead space - non-functional alveoli
3. total dead space - anatomical + alveolar
4. Pulmonary Function Tests
1. spirometer - measures volume changes during breathing
• obstructive pulmonary disease - increased resistance to air flow (bronchitis or asthma)
• restrictive disorders - decrease in Total Lung Capacity (TB or polio)
2. minute respiratory volume (MRV) - total volume flowing in & out in 1 minute (resting rate = 6 L per minute)
3. forced vital capacity (FVC) - total volume exhaled after forceful exhalation of a deep breath
4. forced expiratory volume (FEV) - FVC volume measured in 1 second intervals (FEV1....)
5. Alveolar Retention Rate (AVR)
• AVR = breath rate X (TV - dead space)
• (NORMAL) AVR = 2/minute X (500 ml - 150 ml)
• (NORMAL) AVR = 4.2 L