Physiology Test #4

Emphysema

a type of COPD, in which alveolar tissue is destroyed in a chronic, progressive condition called emphysema -> results in fewer but larger alveoli -> reduces SA -> due to loss of alveoli to exert lateral tension o bronchiolar walls we see a reduction in ability of bronchioles to remain open during expiration •collapse of bronchioles as a result of the compression of the lungs during expiration produces air trapping, which further decreases efficiency of gas exchange in the alveoli most common cause of emphysema is cigarette smoking •cigarette smoke directly and indirectly causes the release of inflammatory cytokines, which promote inflammation by attracting and activating macrophages, neutrophiles and T cells within the lung tissues •proteinases (protein-digesting enzymes) including matrix metalloproteinases secreted from alveolar macrophages and elastase from neutrophils -> leads to destruction of extracellular matrix •proteinase degradation of the extracellular matrix is aided by inactivation of a1-antitrypsin (usually protects lungs from proteinases) -> loss of matrix results in loss of alveoli and enlargement of remaining alveoli

Exercise application: acute mountain sickness

acute mountain sickness occurs in up to 25% of unacclimatized people who arrive at an altitude of 2,500 (8000 ft) and in 85% of people at 4,500 m (15000 ft) •headache is the most common symptom but can be accompanied by malaise, anorexia, nausea, dizziness, and fragmented sleep the low arterial Po2 stimulates vasodilation in the pia mater increasing blood flow within the skull to produce a head ache -> reduced or prevented in normal hyperventilation that accompanies acclimatization to high altitude which produces a low arterial Pco2 (hypocapnia) -> vasoconstriction pulmonary arterioles respond in an opposite way to hypoxia -> constrict rather than dilate -> increased afterload of right ventricle at high altitudes -> can be treated by rest and NSAIDS or descending if needed if more severe more treatment may be needed high-altitude pulmonary edema occurs after a couple of days at altitudes above 3,000 (9000 ft) and produces shortness of breath, cough, and cyanosis, af an altitude of 4,000 (13,000) ft or more for several days a potentially dangerous high altitude cerebral edema can occur and produce confusion, mild fever, and even coma/death -> all of this is less likely if ascent is done gradually •a hemoglobin concentration fo 21 g/dL or greate ris a major symptom of chronic mountain sickeness -> leads to neurological distrubances an dpulmonary hypertension -> heart failure acetazolamide "diamox" is used to prevent and reduce symptoms of altitude sickness -> decreases headache, tireness, nausea, dizziness and shortness of breath, and very useful if you cannot make a slow ascent • best way to prevent altitude sickness is to climb slowly stopping for 24 hours during the climb to allow the body to adjust to the new height and taking it easy the first 1-2 days •acetazolamide is a carbonic anhydrase inhibitor, and a diuretic -> forces kidneys to excrete bicarbonate -> blood becomes more acidic -> fools body into thinking it has excess CO2 compensated by deeper and faster breathing increasing the amount of oxygen in the blood -> not a cure but speeds up acclimatization process

Allergy "hypersensitivity"

allergy "hypersensitivity" refers to particular types of abnormal immune response to antigens, called allergens there are two major forms of allergy; 1. immediate hypersensitivity -> caused by abnormal B cell response to an allergen that produces symptoms within seconds or minutes 2. delayed hypersenstivity -> as seen in TB testing, this is an abnormal T cell response that produces symptoms 24-72 hours after exposure

Chorionic membranes

between days 7-12 as the blastocyst becomes embedded in the endometrium, the chorion becomes a two=cell thick structure consisting of inner cytotrophoblast layer and an outer syncytiotrophoblast layer -> the inner cell mass develops into two layers the ectoderm (nervous system and skin) and endoderm (gut and derivatives) -> the mesoderm is still not apparent at this stage •embryo at this stage is a two-layer-chick disc separated by cytotrophoblast of the chorion by an amniotic cavity as the syncytiotrophoblast invades the endometrium it secretes protein-digesting enzymes -> create numerous blood-filled cavities in the maternal tissue -> cytotrophoblast then forms projections, of villi that grow into pools of venous blood producing a chorion frondosum "leaf-life" structure -> only on side facing uterine wall -> as the embryonic structure grows the other side of the chorion bulges into the cavity of the uterus, loses its villi, and takes on a smooth appearance the placenta asks as an immunological privileged site -> done so by eneration of T reg cells specific for paternal antigens of the fetus •also contains a unique type of killer cells that help remodel the spiral arteries of the uterus to ensure adequate perfusion of blood (if inadequate -> preeclampsia)

Vital Sign: breast feeding may save lives

900 babies would be saved by breastfeeding during the first 6 months of life -> asthma, ear infection, SIDs, leukemia, IgAs, insulin,

Surfactant and Respiratory Distress syndrome

alveolar fluid contains a substance called surfactant (a surface active agent) that reduces surface tension •secreted by type II alveolar cells and consists of phospholipids, primarily phosphatidylcholine and phosphatidylglycerol -> together with hydrophobic surfactant proteins •surfactant spreads between water molecules and disrupts hydrogen bonding reducing surface tension •due to the effect of pulmonary surfactant, the surface tension of the alveoli is negligible •surfactant secreted is removed by alveolar macrophages the ability of surfactant to lower surface tension improves as the alveoli get smaller during expiration •surfactant molecules get more concentrated as alveoli get smaller -> prevents alveoli from collapsing as predicted by law of laplace •even after a forceful expiration the alveoli remain open and a residual volume of air remain in the lungs -> because they do not fully close less surface tension has to be overcome to inflate them next inspiration surface begins to be produced in late fetal life •a normal newborn with partially collapse alveoli must overcome great surface tension during their first breath ~15-20X the transpulmonary pressure required for a normal breath •if the baby is premature and its lungs have not fully matured this force required is duplicated in every breath due to lack of surfactant production

Microscopic structure of the kidney

The nephron is the functional unit of the kidney responsible for the formation of urine -> 1,000,000 or more in a single kidnye -> consists of small tubules and small blood vessels -> fluid formed by capillary filtration enters the tubules and is subsequently modified by transport processes -> the resulting fluid is known as urine (site of absorption/secretion = filtrate, once emptied into calyx = urine) Renal blood vessels •arterial blood enters into the kidney thorugh the renal artery which divides into interlobar arteries that pass between the pyramids through renal columns •arcuate "bow-like" arteries branch from the interlobar arteries at the boundary of the cortex and medulla •a number of interlobular arteries radiate from the arcuate arteries inot the cortex and subdivide into numerous afferent arterioles that lead to glomeruli, capillary networks that produce a blood filtrate that enters urinary tubules •remaining blood in glomerulus leaves through efferent arteriole which delivers the blood into another capillary network "peritubular capillaries" surrounding renal tubules arrange of blood vessels is unique -> only one in body where a capillary bed (glomerulus) is drained by an arteriole rather than a venule -> delivered to a second caillary bed located downstream (peritubular capillaries) -> blood is then drained into veins that parallel the course of the arteries in the kdiney -> interlobular, arcuate, and interlobar veins •interlobar vein descend between the pyramids, converge, and leave the kidney as a single renal vein -> empty into inferior vena cava Nephron Tubules •The tubular portion of a nephron consists of; •glomerular capsule •proximal convoluted tubule •descending limb of loop of henle & ascending loop of henle •distal convoluted tubule The glomerular (bowman's) capsule surround the glomerulus -> together they are located in the cortex of the kidney and together constitute the renal corpuscle •the glomerular capsule contains an inner visceral layer of epithelium around the glomerular capillaries and an outer parietal layer -> space between the two is continuous with the lumen of the tubule and receives the glomerular filtrate the filtrate that enters the glomerular capsule passes into the lumen of the proximal convoluted tubule •wall of the the proximal convoluted tubules consists of a single layer of cuboidal cells containing millions of microvilli -> increase SA for reabsorption -> form a "brush border" •process of reabsorption of NaCl, Water, and other molecules needed by the body are transported from the lumen through tubular cells into surrounding peritubular capillaries the glomerular, glomerular capsule, and convoluted tubule are located in the renal cortex •fluid passes from the proximal convoluted tubule -> nephron loop "loop of henle" -> carried into renal medulla by descending limb of loop and returns to the cortex through the ascending loop -> once again becomes coiled and makes up the distal convoluted tubule -> shorter and less microvilli than the proximal -> empties into a collecting duct •due their transport properties, the nephron loops, distal convoluted tubule, and collecting duct participate in final urine output and are critical in homeostasis of blood volume and pressure the two principal typees of nephrone are classified according to their positions in the kidney and lenths of their loops of henle •those that originate in the inner 1/3 of the cortex -> juxtamedullary nephrons and are next to medulla, and have longer nephrone loops •cortical nephrons -> originate in the outer 2/3 of the cortex a collecting duct receives fluid from several nephrons -> fluid is drained from the cortex to the medulla as the collecting dcut passes through a renal pyramid -> fluid now called urine passes through a minor calyx -> urine is then funneled through the renal pelvis and out the kidney in the ureter

Autoimmune diseases

autoimmune diseases -> result of failure of the immune system to recognize and tolerate self-antigens -> results in activation of autoreactive T cells and production of autoantibodies by B cells -> leads to inflammation and organ damage •cell division of B cells within germinal centers of lymph nodes increases antibody diversity through somatic hypermutation and Ig class switching -> production of autoreactive B cells occurs as an inevitable byproduct -> autoimmune diseases result when these cells become exposed to the appropriate self-antigen 5-7% of the population have one of 40 known autoimmune diseases with a third of that group being women -> due to women's immune system being more efficient, and have twice as miuch antibody response to the flu (may also be correlation with fetal cells) •most common diseases are rheumatoid arthritis, type 1 diabetes, MS, grave's disease, glomerulonephritis, thyroiditis, pernicious anemia, psoriasis, and system lupus erythematosus (SLE) there are 6 reasonswhy self-tolerance may fail; 1. an antigen that normally doesn't circulate in the blood becomes exposed -> thyroglobulin protein when exposed creates the autoimmune disease Hashimoto's thyroiditis, similiarly lens protein from a damaged eye can lead to sympathetic ophthalmia 2. a self-antigen may be altered by combining with a foreign hapten --thrombocytopenia (low platelet count) can be caused by autoimmiune destruction of platelets -> occurs when drugs acting as haptens such as aspirin, penicillin, sulfonamide, antihistamines, digoxin, and others combine with platelet proteins to produce new antigens ---symptoms usually disappear once the patient stops taking the drug 3. antibodies may be produced that are directed against other antibodies --a necessary part of prevention of autoimmunity, but can be an issue when an imbalance occurs --rheumatoid arthritis -> IgM antibodies attack IgG antibodies -> leads to inflammation reactions of the joints 4. Antibodies produced against foreign antigens may cross-react with self-antigens --can be causesd by bacterial infections such as streptococcus -> antibodies produced in response to bacteria cross-react with self-antigens in the heart and kidneys -> can produce heart damage (rheumatic fever), and damage to glomerular capillaries in the kidneys (glomerulonephritis) 5. self-antigens such as receptor proteins may be presented to the helpter T cells together with class-2 molecules --normally only antigen-presenting cells produce class 2 MHC molecules, associated with foreign antigens and recognized by helpter T cells -> as a result of an infection cells that do not normally produce class-2 MHC molecules may do so and present a self-antigen to the helpter T cells -> in graves' disease through this process autoantibodies against the TSH receptor protein are made, these are called TSAb's (thyroid-stimulating antibody) and interact with the TSH receptors overstimulating them 6. Autoimmune disease may result when there is inadequate activity of regulatory (suppressor) T lymphocytes --reg T cells dampen the immune response -> supress autoimmune diseases and chronic inflammation associated with them --through FOXP3 other T cells can convert into reg T cells -> inadequate expression of this gene can lead to insufficient activity causing autoimmune diseases

Clinical application: Cord blood banking

blood from umbilical cord contains stem cells that can be saved for later in life when the child might need them to reconstitute a hematopoietic system if bone marrow is destroyed (ex. leukemia) •risk free procedure but is expensive with a low probability of need genetic screening of neonates "newborns" is done on blood obtained by a heel prick when the baby is 24-48 hrs old •required and 20-30 tests are ran on it such as phenylketonuria (PKU), CFTR, lysosomal stroage diseases, and others such as tests for endocrine disoders (hypothyroidism) and hemoglobin disorders (sickle-cell)

Glomerular filtration

endothelial cells of glomerular capillaries have large pores (200-500 å) called fenestrae -> allows for glomerular capillareis to be 100-400x more permeable to plasma than skeletal muscles before the fluid in blood plasma can enter the interior of the glomerular capsul it must pass through three layers that serve as filters hence the name "filtrate" -> after modification the resulting fluid is urine 1. capillary fenestrae -> allow proteins to pass but are surrounded by charges that prevent a barrier to plasma proteins (change in charge is seen in preclampsia) 2. glomerular basement membrane -> layer of collagen IV and proteoglycans lying outside the capillar endothelium -> another barrier to plasma proteins (defects can lead to glomerulonephritis seen in alport's syndrome) -> 5x as thick as other basement membranes -> restricts rate of fluid flow 3. inner (visceral) layer of the glomerular capsule -> composed of podocytes unique to epithelial cells with a bulbous cell body, an dprimary processes extendin from the cell body and thousands of food processes that branch from the primary processes -> feet interdigitate (clasp together) creating narrow slight diaphragms analogous to desmosome, or zona adherens all dissolved plasma solutes easily pass however proteins are excluded by their large size and net negative charges -> evidence suggest the slit diaphragm poses the majro barrier to the passage of plasma proteins into the filtrate -> defects in this region can lead to proteinuria (protein in urine) a small amount of albumin can enter the filtrate, but less than 1% of this is excreted as urine with the majority being reabsorbed in the proximal tubule by receptor mediated endocytosis -> thus proteinuria occurs upon saturation of these receptors glomerular ultrafiltrate is fluid that enters the glomerular capsul because it is formed under hydrostatic pressure of the blood formed by left ventricular systole (QRS complex, contraction, etc.) -> similar to the formation of tissue fluid by other capillary beds in the body's response to starling forces •severe dehydration -> leads to hypotension -> reduction in blood volume and pressure leads to increased transit time to move wastes from tissues to kidneys, increasing the retention of metabolic wastes -> also leads to decrease in glomerular filtration rate (driven by pressure) -> increasing retention of wastes -> end result is acidosis "uremia", impaired cell metabolism, and death the force favoring filtration is opposed by a counterforce developed by the hydrostatic pressure of fluid in the glomerular capsule •the low protein concentration of the tubular fluid compared to plasma promoting the osmotic return of filtered water •when these opposing forces are subtracted from the hydrostatic pressure of the glomerular capillaries, a net filtration pressure of about 10 mmHg is obtained -> due the permeable nature of the capillaries this allows for a large volume of filtrate (not urine) to be produced glomerular filtration rate (GFR) is the volume of filtrate produced by both kidneys/min -> averages 115 mL/min in women and 125 mL/men -> 7.5 L/hour or 180L/day (45 gallons) •since total blood volume is 5.5 L, every 40 min the total blood volume is filtered -> most filtered water is returned regulation of GFR -> is caused by vasoconstriction/dilation of afferent arterioles affecting rate of blood flow to glomerulus -> result of extrinsic regular mechanisms (sympathetic nerve innervation) and intrinsic regulatory mechanisms "autoregulation" -> together these ensure that GFR is high enough to allow kidneys to eliminate wastes and regulate blood pressure but not cause excessive water loss Sympathetic nerve effects -> occur during fight-or-flight and exercise -> stimulates vasoconstriction -> preserves blood volume and diverts blood to the muscles and heart •similar effect seen in cardiogenic shock -> helps to compensate for the rapid drop in blood pressure

Renal control of electrolytes and acid-base balance

kidneys help regulate concentrations of plasma electrolytes (Na, K, Cl, HCO3, Sulfate, phosphate) •sulfate and phosphate ion concentrations are primarily determined by proximal tubules •parathyroid hormone (PTH) secretion -> stimulated by a fall in plasma Ca++ acts on kidneys to derease reabsorption of phosphate •control of Na is important in regulation of blood volume and pressure •regulation of K+ is important in proper function of cardiac and skeletal muscles role of aldosterone in Na+/K+ Balance •90% of salt is reabosrbed in the early part of the nephron before reaching the distal tubule -> occurs as a constant rate w/o hormone reguation -> final conentration of salt in urine is vareid according to eh needs of the body by processes in the late distal tubule and in the cortical region of the collecting duct •renal reabsorption of Na+ and secretion of K+ are regulated by aldosterone the principal mineralocorticoid secreted by the adrenal cortex -> secreted in response to angiotensin II and blood Na+ and volume are low and in response to high blood K+ Sodium reabsorption •90% is absorbed in earlier portions, and 80% of what remains is reabsorbed through wall of tubule into the peritubular blood -> represents 8% of amount filtered -> 2% left is what aldosterone acts on w/o hormone it is excreted -> this 2% is 30 g over the course of the day -> if alosterone is secreted in max amounts all Na+ is absorbed -> aldosterone stimulates Na+ reabsorption to some degree in the late distal convoluted tubule -> primary site of aldosterone action is in the cortical collecting duct, located in the renal cortex initially and has different permeability properties than the terminal portion in the medulla •aldosterone acts on Na+/K+ ATPase pumps in basolateral membrane of cortical collecting cells -> electrochemical gradient for passive movement of Na+ from the filtrate, through Na+-Cl- cotransporters in the apical membrane (facing the lumen) -> diffusion of Na+ creates a negative charge drawing Cl- along to preserve charge -> transporter is the target of thiazide diuretics Potassium secretion •90% absorbed in earlier portion •late distal tubule and cortical collecting duct are the target of aldosterone for K+ -> K+ in a meal eaten is higher than K+ in plasma -> secretion of K+ into filtrate by late distal tubule and collecting duct to increase elimination of excess K+ •eating a meal rich in K+ raises blood K+ -> stimulates adrenal cortex -> release of aldosterone -> stimulates late distal tubule and cortical collecting duct to increase secretion of K+ into filtrate •secretion of K+ can also occur w/o aldosterone in which a rise in blood K+ directly causes more K+ channels to become inserted in apical membranes of the late distal tubule and cortical collecting ducts -> removed when K+ concentrations fall below normal by endocytosis •secretion of K+ involves the transport of K+ across the basolateral membrane by Na+/K+ ATPase pump followed by diffusion of K+ into the filtrate through K+ channels on apical membrane -> diffusion of K+ apical membrane is driven by reabsorption of Na+ creating a potential difference that favors K+ diffusion into filtrate -> an increase in Na+ content in filtrate will cause increased removal of K+ •increased Na+ and water in filtrate can stimulate juxtaglomerular apparatus to secrete renin -> activate renin-angiotensin-aldosterone system -> increased aldosterone secretion stimulates more Na+ reabsorption and K+ secretion distal tubule cells contain primary cilium that protrudes into the lumen -> bending from filtrate activates K+ channels and lead to increased K+ secretion into the filtrate these mechanisms explain how diuretic drugs can produce hypokalemia (low K+) •diuretics act to inhibit Na+ transport in the nephron loop and increase delivery of Na+ to the distal tubule •thiazide diuretics -> inhibit the Na-Cl cotransporters -> increased amount of Na and water to be delivered downstream to the late distal tubule and cortical collecting duct -> increased sodium flow stimulates Na/K exchange to promote Na+ reabsorption to counteract the thiazide's diuretic effect and K+ secretion -> excessive urinary loss of K+ requiring those on these drugs to take K+ supplements control of aldosterone secretion •aldosteron promotes Na+ retention and k+ loss -> aldosterone is increased when there is low Na+ or high K+ concentration in blood •rise in plasma K+ concentration depolarizes the aldosterone-secreting cells of the adrenal cortex stimulating aldosterone secretion • a decrease in Na+ has an indirect effect -> decrease plasma Na+ occurs with a fall in blood volume -> actives renin-angiotensin-aldosteron system

Physical properties of luns

lungs must be able to expand when stretched -> need for high compliance •for expiration ot occur the lungs must bet smaller when this tension is released -> must have elasticity, the ability to recoil to original dimensions -> aided by surface tension forces within the alveoli

Immediate Hypersensitivity

production of allergic rhinitis (runny/stuff nose), conjunctivities, allergic asthama, atopic dermatititis (urticaria/hives), and food allergies •result of immune response from an allergen -> those who are not allergic the allergen stimulates one type of helpter T cell, the Th-1 cells -> secretion of interferon-y and interleukin-2 •those who are allergic stimulate another type of helper T cell, the Th-2 cell -> secretion of lymphokines such as interleukin-4 and interleukin-13 -> recruit eosinophils promoting mucus production from goblet cells, and stimulat smooth muscles in the bronchioles to promote airway hyperresponsiveness of asthma --these lymphokines also stimulate B cells and plasma cells to secrete antibodies of the IgE subclass instead of normal IgG antibodies -> IgE antibodies protect against wormlike helminth parasites (from raw meat) but also mediate allergic immediate hypersensitivity reactions IgE antibodies are concentrated in mucosal membranes •there, constant fragment (Fc) bind to receptor proteins on the surface of mast cells and basophils •once an individual is exposed to the an allergen, the allergen binds to these IgE antibodies -> the allergen cross-links the IgE bound to its receptors on the mast cells and basophils -> release of histamine and other cytokines (prostaglandins, and leukotrienes) -> produce immediate hypersensitivity reactions •histamine stimulates bronchoconstriction, but vasodilation in blood vessels -> histamine also increases capillary permeability promoting the exit of plasma proteins and fluid producing localized edema •histamine influences the specific immune response, promoting the release of inflammatory cytokines •the symptoms of hay fever are produced largely by histamine can be effectively treated by antihistamine drugs that block the H1-histamine receptor in asthma the difficulty in breathing is caused by bronchioconstriction of bronchioles as a result of leukotrienes secreted by eosinophils -> treated with epinephrine and more specific ß-adrenergic stimulating drugs -> bronchodilator, and with corticosteroids, which inhibits inflammation dnleukotriene synthesis certain foods can provoke IgE-mediated allergic response as well in susceptible people •through T reg cells the digestive tract usually tolerates dietary antigens -> in food allergies the food allergens can evoke IgE-mediated responses that lead to gastrointestinal disorders, urticaria (hives), hypotension, and inflammation of the bronchioles •some allergic food reaction can be mediated by Th-2 cells rather than IgE mechanisms •food allergies differ from food intolerance which is caused by enzyme issues •symptoms of food allergies can be reduced by antihistamines, and epinephrine Immediate hypersensitivity to a particular antigen can be tested by injecting various antigens under the skin •within a short time a flare-and-wheal reaction is produced if a person is allergic -> the flare component is caused by spreading flush of vasodilation, while the wheal (elevated area) is caused by local edema allergens that provoke immediate hypersensitivity include various foods, bee stings, and pollen grains •most common type is seasonal hay fever provoked by ragweed (ambrosia) pollen •those with chronic allergic rhinitis and asthma can be caused by allergy to dust or feathers with dust mites caused by its feces and enters nasal mucosa like pollen (100,000 mite feces per gram of house dust)

Acid-Base balance of the blood

the blood plasma within arteries has a pH normally between 7.35-7.45 (recall pH is 0-14, so we alkaline) because CO2 is a volatile gas released during expiration, carbonic acid is referred to as a volatile acid -> significant because blood concentration is uniquely regulated by breathing •all other acids of teh blood including lactic acid, fatty acids, ketone bodies, etc. are nonvolatile aids that cannot be normally eliminated through ventilation (exception of ketoacidosis during diabetes where concentration is so high it is expelled by breathing) •under normal conditions H+ released by nonvolatile metabolic acids does not affect the blood pH because these hydrogen ions are bound to molecules that function as buffers -> major buffer in the plasma is bicarbonate -> limited by amount (eventually all will converted by to carbonic acid) -> if this were to occur H+ would increase and pH would drop -> to avoid this excess H+ is removed in urine -> therefore the kidneys are responsible for mainting a normal concentration of free bicarbonate in the plasma a fall in pH below 7.35 is called acidoses, while a rise above 7.45 is called alkalosis -> both of these conditions are categorized into respiratory and metabolic components of acid-base balance an acid-base distrubance caused by abnormal arterial CO2 levels, is described as "respiratory" acidosis or alkalosis •respiratory acidosis -> caused by hypoventilation -> rise in [CO2] and carbonic acid •Respiratory alkalosis -> hyperventilation -> drop in CO2 and carbonic acid acid-base distrubance caused primarily by abnormal changes in plasma bicarbonate levels is described as "metabolic" •metabolic acidosis -> excessive production of nonvolatile acids -> ketone bodies (diabetes) or lactic acid -> release of H+ combines with bicarbonate reducing free bicarbonate concentration. -> can also occur due to excessive loss of bicarbonate to diarrhea eliminated through pancreatic juice -> lack of free bicarbonate •metabolic alkalosis -> too much bicarbonate, or inadequate nonvolatile acids (from vomiting -> loss of gastric juice normally absorbed in intestine) to combine both groups we compared normal arterial blood pH as a ratio of bicarbonate to CO2 in a 20:1 ratio an acid-base disturbance of the respiratory or metabolic component is partially compensated for by a secondary change in the other component (if primary distrubance is metabolic, secondary changes in ventilation will occur to reach a stable arterial Pco2 within hours) Ventilation and Acid-base balance •acid-base balance of blood is divided into the respiratory component and the metabolic component •respiratory component -> CO2 concentraiton of the blood as a measurement of Pco2 -> regulated by respiratory system •metabolic component -> controlled by kidneys ventilation is adjusted to keep pace with the metabolic rate so that arterial Pco2 remains in normal range •in hypoventilation -> ventilation is insufficient to blow off CO2 and maintain a normal Pco2 -> high Pco2 -> high carbonic acid -> respiratory acidosis •in hyperventilation -> ventilation is greater than rate of CO2 production -> Pco2 decreases -> raises pH -> respiratory alkalosis -> dizziness occurs as pH of the CSF and brain instertial increases causing vasoconstriction -> can also lead to tetanic contractions as an decrese of Ca++ is present, being bound to albumin making the nerve cells highly excitable -> hypocalcemic tetany as a change in blood pH, produced by alteration in either the respiratory or metabolic component of acid-base balance is partially compensated by the other •ex. a person with metabolic acidosis will hyperventilate -> caused by aortic and carotid bodies are stimulated by an increased blood H+ concentration -> as a result of hyperventilation, a secondary respiratory alkalosis is produced -> person is still acidotic but not as much -> characterized by a low pH accompanied by a low blood Pco2 as a result of hyperventilation •similarly, metabolic alkalosis -> compensated by retention of carbonic acid by hypoventilation

Vital Signs: where did it go?

ultrascreen showed twins -> fraternal twins shown by separate membranes -> likely related to her late age (39) -> due to increase in FSH helping more eggs to mature with age more than half of women who have twins, miscarry one of them one of the twins was viable while the other had shrunken and died

Pulmonary Fibrosis

under certain conditions, for unknown reasons, lung damage leads to pulmonary fibrosis instead of emphysema •normal structure of the lungs is disrupted by accumulation of fibrous connective tissue proteins •can result from inhalation of particles less than 6µm -> accumulation in respiratory zone -> diseases such as anthracosis "black lung" fall into this category

Exercise application: cigarette smoking

Cigarette smoking -> promotes obstructive lung disorders as measured by a reduced FEV, FEV normally declines with age, but this is accelerated in smokers rate of decline in smokers with mild COPD who quit was found to be less than in those that continued to smoke air pollution has been found to significantly affect the FEV of children with asthma, and has been related exercise on smoggy days

Clinical Application: Ondine's curse

Ondine's curse -> potentially fata apnea during sleep due to brainsteam dysfunction •voluntary regulation of breathing is not affected because it involves descending corticospinal tracts from the cerebral cortex -> during sleep though a compromised automatic control causes apnea ranging from mild to fatal -> can be caused by trauma but is more often congenital "congenital central hypoventilation syndrome (CCHS) -> the defective gene has been identified and shown to influence the retrotrapezoid nucleus of the medulla oblongata which responds to a rise in Pco2 and to input from the carotid bodies patients with CCHS require a tracheostomy and a mechanic ventilator throughout their lives

Clinical application: mifepristone "mifeprex"

a synthetic steroid that works as a progesteorn receptor antagonis to block progesteron action -> promotes abortion in early pregnancy and is called the "abortion pill" develed in france initially and called RU-486 -> approved for preganancies less than 49 days mifepristone is used together with a prostaglandin such as misoprostol "cytotec" to cause abortion -> but this can also be used in low doses as an emergency contraceptive after unpotected sex -> known as "morning after pill" •also has anti-glucocorticoid and anti-progesteorn actions -> can be used as treatment for Cushing's syndrome

Clinical application: diabetes insipidus

characterized by polyuria (large urine volume ~3-10 L/day), thirst, and polydipsia urine is dilute with a hypotonic concentration less then 300 mOsm two major types of diabetes •central diabetes insipidus -> inadequate secretion of ADH •nephrogenic diabetes insipidus -> inability of the kidneys to respond to ADH distinguished by measuring ADH and charging the kidneys with a synthetic ADH called desmopressin nephrogenic diabetes insipidus may be caused by genetic defects in the aqua porin channels or the ADH receptors -> often a result of drug therapy (ex. lithium given in bipolar disorders, and certain antibiotics) people with central diabetes insipidus can take desmopressin when needed and those with nephrogenic diabetes insipidus must drink a lot to prevent dehydration

Hemoglobin and oxygen transport

if proper functioning lungs blood leaving the pulmonary veins and traveling in system arteries has a Po2 of 100 mmHg, and .3 mL/100mL plasma oxygen concentration -> this concentration is dependent on both the Po2 and hemoglobin concentration -> arterial blood can carry 1.34 mL of oxygen per gram of hemoglobin -> if Po2 and [hemoglobin] are normal blood carries approx. 20 mL/100mL O2 Hemoglobin •oxygen in blood for the most part if bound chemically to hemoglobin -> hemoglobin consists of four polypeptide chains called globin and four iron-containing dis-shaped organic molecules known as hemes •the protein part of hemoglobin is composed of two identical alpha chains, 141 AA, and two identical beta chains, 146 AA long -> together make one heme group -> within group is Fe which combine one molecule of O2 -> therefore one hemoglobin can carry four oxygen molecules -> there are roughly 280 million hemoglobin molecules in one RBC (1 billion O2 molecules) •normal heme contains iron in a reduced form (Fe++ "ferrous iron") -> in this form iron can share e- and bond to Oxygen to form oxyehmoglobin -> upon dissociation of Oxygen to tissues the heme group is stil in the reduced Fe++ form and hemoglobin is called deoxyhemoglobin or reduced hemoglobin -> thus oxyhemoglobin is not an oxidized hemoglobin due to no exchange in e- upon binding •oxidized hemoglobin, methemoglobin has iron in a Fe+++ "ferric iron" state -> lacks electron needed to bond with oxygen -> certain drugs can increase the amount •the body produces some carbon monoxide which can bind to hemoglobin to form carboxyhemoglobin, not to be confused with carbaminohemoglobin which is CO2 bound to hemoglobin -> small amounts of carboxyhemoglobin is normal, in large amounts this can be dangerous to the higher affinity of CO vs. O2 the percent oxyhemoglobin saturation (oxyhemoglobin/total hemoglobin) is measured to assess how well the lungs have oxygenated the blood -> normally around 97% with varying amount of the other forms making up the rest -> can be separated by color •oxyhemoglobin - tomato juice color •carboxyhemoglobin - cranberry juice •oxygen saturation is measured using a pulse oximeter, or more precisely with a blood-gas machine Hemoglobin concentration, is a measurement of the oxygen-carrying capacity of whole blood •below normal is called anemia -> above normal occurs in conditions such as polycythemia "high RBCs" which occur as a result of life at high altitude •production of hemoglobin and RBCs in the bone marrow is controlled by erythropoietin produced by kidneys in response to tissue hypoxia -> stimulated by low oxygen delivery to kidneys, although RBC production is also promoted by testosterone resulting in men have [hemoglobin] increase of 1-2 g/100mL more than women loading and unloading reactions •deoxyhemoglobin and oxygen combine to form oxyhemoglobin-> called loading reaction -> dissociation is the reverse and known as a unloading reaction •loading occurs in the lungs and unloading in systemic capillaries • deoxyhemoglobin + O2 <-> oxyhemoglobin •the oxtent to which the reaction will go in each reaction depends on two factors; 1. the Po2 of the environment 2. the affinity, or bond strength, between hemoglobin and oxygen •high Po2 drives the equation to the right (loading) occurring at the high po2 of pulmonary capillaries •conversely in systemic capillaries the low Po2 drives the rxn to the left (unloading) affinity also plays a role between hemoglobin and oxygen -> a strong bond would favor loading, while a weak bond favors unloading -> bond strength varies from a location in accordance to loading vs. unloading

Clinical application: BNP

in addition to atrial natriuretic peptide B-type natriuretic peptide (BNP) hormone is secreted in response to increased volume and pressure in ventricles -> acting like ANP to promote diuresis, however it also causes congestive heart failure (CHF) -> allowing for its presence to be used in diagnosis of CHF -> allowing for distinguishing cardiac vs. pulmonary causes of a patient's dyspnea (difficulty breathing)

Significance of Blood Po2 and Pco2 measurements

blood Po2 measurement is not directly affected by O2 in RBCs -> Po2 is not a measurement of the total oxygen content of whole blood, just plasma -> however, it does provide an index of good lung function •if inspired iar has a normal Po2, but arterial Po2 is below normal ( 5mmHg or more) -> indicates impaired gas exchange of the lungs measurement of arterial Po2 can thus provide information in treating those with pulmonary disease, performing surgery, and premature babies when lungs are performing properly the Po2 of systemic arterial blood is only 5 mmHg less than the Po2 of alveolar air -> a normal Po2 of 100 mmHg -> hemoglobin is loaded with O2 "oxyhemoglobin saturation" or 97% oxyhemoglobin/total hemoglobin -> due to high percentage breathing 100% oxygen from a tank does not make a large difference (+~3%) -> can change O2 dissolved in plasma due to the higher Po2 (if Po2 doubles, the dissolved oxygen doubles -> whole blood only slightly increases) •this is due to the small amount of oxygen in plasma compared to RBCs however, because O2 is carried by RBCs it must be dissolved in plasma before dissolving into tissue cells, a doubling of blood Po2 -> rate of oxygen diffusion would double (in the ex. above) -> how hyperbaric oxygen treatment functions -> no evidence that pure air helps athletic performance you can also measure dissolved CO2 using a electrode, in veins we see a Po2 of 40 mmHg, and a Pco2 of 46 mmHg -> after gas exchange this changes to a Po2 of 100 mmHg, and a Pco2 of 40 mmHg •arterial blood is fairly constant in these values, while venous blood varies greatly (ex. excercise vs. doing nothing)

Vital Signs: A boy grasping for his life, and the medic's rescue measures have failed

16 year old asthmaticus, and cyanotic •boy woke up not being able to breath and his inhaler and epinephrine from the medics had no effect -> inserted a laryngoscope blade but the body has blocked off the entry -> after a moment the tube enters the boy has oxygen asthma kills 5,000 each year, up 50% from the 1980s -> evidence shows that it is caused by bronchial inflammation rather than muscle twitches as previously thought •asthmatics airways are packed with eosinophils •50% more likely to be seen in african-americans than whites, and 4x more likely to die from it magnesium is used in extreme cases -> relieves constriction •use of leukotriene modifier drugs -> blocking eosinophil products

Clinical Application: Tracheotomy

A tracheotomy is a surgical procedure to create a hole in the trachea -> it is then called a tracheostomy (name of hole) -> tubes are inserted into the hole tracheostomies are usually done in the hospital to allow the patient ot breathe with the aid of a mechanical ventilator, but they can be performed by a surgeon in an emergency to allow a person to breath when the trachea becomes occluded by aspiration of a foreign object, trauma, or inflammation

Vital Signs: When a woman collapses in the waiting room, a doctor acts swiftly to diagnose and treat a potentially fatal condition

ABCs "airway, breathing, circulation" women entered hospital and collapsed, she passed the ABC test and after about a minute regained her composure and was "fine" the culprit in nearly all cases of syncope is an interruption in blood flow to the brain -> most commonly from vasovagal faint in which the vagus nerve sends signals that dramatically slow the heart, the signals can be provoked in susceptible people by distress they feel such as sight of blood •cardiac rhythm disorders account for another 10% -> low cardiac output -> insufficient in brain leading to fainting •another 10% are caused by orthostatic hypotension •in 2% the cause is unkown women had eaten some peppers the night before that had tasted "off" the next morning felt sick and decided to visit the hospital -> she had low blood flow to the brain -> her systolic pressure was 70, compared to the healthy 120 -> possibly caused by anaphylactic shock a severe allergic reaction mediated by the body's immune system in an anaphylactic reaction -> floods of chemicals primarily histamine are put into the bloodstream -> blood vessel dilation -> pooling of blood in extremities instead of flowing back to the heart -> cardiac output falls -> blood pressure drops injected her with epinephrine (adrenaline) -> restores tone to blood vessels and ramps up the strength and speed of cardiac action put her on an IV -> helps to restore volume of liquid circulating through arteries use of oxygen to maximize delivery to tissues she recovered but would need to do an allergy test to determine what caused it and carry an injectable epinephrine pen at all times

Air upon entering the trachea goes through what process?

Air enters the trachea from the pharynx, a cavity behind the palate that receives the contents of both the oral and nasal passages -> to enter or leave the trachea and lungs air must pass through valvelike opening called the glottis "vocal cords" -> the ventricular folds and vocal folds are part of the larynx "voice box" which guards the entrance to the trachea •the projection at the front of the throat, termed "adam's apple" is formed by the largest cartilage of the larynx the conducting zone of the respiratory system, consists of the mouth, nose, pharynx, larynx, trachea, primary bronchia, and all successive branchings of the brionchioles up to the terminal bronchioles -> in addition to conducting air into the respiratory zone these structions aslso serve to warm, humidify, filter, and clean the air •regardles of outside temp, when air reaches the respiratory zone it is 37˚C and is saturated with water vapor -> ensures constant internal body temp and protection of lung tissue from desiccation mucus secreted by cells of conductiong zone servest to trap small particles and performs a filtration function -> mucus is moved along at a rate of 1-2 cm per minute by cilia (monocililary escalator) projecting from the tops of epithelial cells tha tline the conducting zone -> there are 300 ciliar per cell that move together to bring mucus to pharynx where it can be removed by swallowin or expectorating in a process known as mucociliary clearance •in CFTR the mucociliary escalator fails to function properly due to the reduced secretion of Cl- with increased aborption of Na+ -> leads to mucus with a reduced water content that is too thick for the cilia to properly clear •cigerette smoking has been shown to damage cilia and reduce mucociliary clearance as a result of this filtration particles larger than 6µm do not normally enter the respiratory zone of the lungs •ex. black lung caused by carbdon dust on coal is small enough to enter and causes pulmonary fibrosis •resident macrophages clean alveoli and can help relieve symptoms of carbon dust -> hence there other name as dust cells -> this cleansing action of cilia and macrophages is diminished by smoking

Clinical Application: Asthma medications

Asthma medications fall into different categories •quick acting beta-agonists (albuterol) -> stimulate the ß2-adrenergic receptors in the pulmonary smooth muscle to dilate the bronchioles are used to rescue during asthma attack •long acting beta agonists -> stimulate ß2-adrenergic receptors but effects last for more than 12 hours -> generally combined with glucocorticoid to inhibit inflammation and are used for asthma control over a period of weeks rather than for rescue from an attack •inhaled, or IV corticosteroids are sometimes given for serious attacks •leukotriene receptor antagonists (montelukast "Singulair") are pills now often used for long-term alleviation of asthma symptoms

carbon dioxide transport

Carbon dioxide is carried by blood in three forms; 1. dissolved CO2 -> in the plasma, CO2 is 21x more soluble than O2 in water and 1/10 of the total blood CO2 is dissolved in plasma 2. as carbaminohemoglobin -> 1/5 of total blood CO2 is carried attached to an AA in hemoglobin 3. bicarbonate ion -> account for the majority carried by the blood carbon dioxide can also combine with water to form carbonic acid -> occurs spontaneously in the plasma at a slow rate -> but is very rapid in RBCs due to carbonic anhydrase -> an enzyme confined to RBCs •formation of carbonic acid from CO2 and water is favored by high Pco2 in capillaries of systemic circulation (ex. law of mass action, where in a balanced equation changing the reactants or products changes balance) The chloride shift •as a result of the catalysis by the enzyme within RBCs large amounts of carbonic acid are produced as blood passes through the systemic capillaries -> buildup of carbonic acid in the RBC favors the dissociation of these molecules into hydrogen ions and bicarbonate •the hydrogen ions are buffered by their combination with deoxyhemoglobin within RBCs -> unbuffered H+ ions diffuse into plasma, although more bicarbonate diffuses outware than H+ •trapping of H+ ions in RBCs by attachment to hemoglobin and removal of bicarbonate result in a net postive charge (+) -> attracts Cl- -> exchange of anions as blood travels through tissue capillaries is known as the chloride shift -> unloading of oxygen is increased by the bonding of H+ to oxyhemoglobin, this bohr effect results in increased conversion of oxyhemoglobin to deoxyhemoglobin -> deoxyhemoglobin binds H+ more strongly allowing for the act of unloading O2 improves the ability of hemoglobin to buffer the H+ released by carbonic acid •removal of H+ from the solution further drives the enzyme to produce more carbonic acid increasing the ability of the blood to transport CO2 -> by doing so CO2 enhances oxygen unloading and oxygen unloading improves carbon dioxide transport -> how exercising muscles help drive O2 to the site Reverse chloride shift •upon reaching the pulmonary capillaries deoxyhemoglobin is converted to oxyhemoglobin -> weaker affinity for H+ -> H+ are released attracting bicarbonate -> combines with H+ to form carbonic acid -> occurs under conditions of low Pco2

Chemoreceptors in the Medulla and peripheral

Chemo receptors in medulla •most sensitive to changes in arterial Pco2, located in the ventrolateral surface of the medulla oblongata near the exit of the 9th and 10th cranial nerves •nerve in the region are sensitive to pH -> low pH elicits increased ventilation •an increase in arterial Pco2 causes a rise in the H+ concentration of the blood as a result of increased carbonic acid concentrations -> H+ in blood can stimulate the peripheral chemoreceptors, but cannot cross the blood-brain barrier, and can't influence the medullary chemoreceptors •CO2 in arterial blood can cross the blood-brain barrier and lower the pH of cerebrospinal fluid (CSF) and brain interstitial fluid -> lower pH (increased H+) of brain interstitial fluid stimulates the chemoreceptors in the medulla •the chemoreceptors in the medulla are ultimately responsible for 70-80% of increased ventilation that occurs in sustained rise in arterial Pco2 -> response can take several minutes, however the immediate increase in ventilation that occurs when Pco2 rises is produced by stimulation of the peripheral chemoreceptors Peripheral chemoreceptors •the aortic and carotid bodies are not stimulated directly by blood CO2 -> they are stimulated by a rise in the H+ concentration (fall in pH) of arterial blood -> occurs when blood CO2 and carbonic acid is raised •in summary, the retention of CO2 during hypoventilation (rapidly) stimulates the peripheral chemoreceptors through a lowering of blood pH -> rapid response (note -> anything that lowers blood pH will have a similar response) •the central chemoreceptors respond to the fall in the pH of their surrounding interstitial fluid, stimulating a steady-state increase in ventilation if the blood CO2 remains elevated *these are different neurons than those in the rhythmicity center

Renal plasma clearance

Clearance refers to the clearing of the blood of excess ions and waste products accomplished through excretion in the urine -> leads to concentration of these substances to be less in blood leaving the kidneys than blood entering Transport process affecting renal clearance •renal clearance -> ability of the kidneys to remove molecules from the blood plasma by excreting them in the urine -> what is not reabsorbed will be eliminated from the blood the process of filtration, a type of bulk transport through capillaries promotes renal clearance -> process of reabsorption involves carrier proteins -> more particular molecules and ions from filtrate back into blood, reducing renal clearance for these molecules in the process of secretion, it is the opposite of reabsoprtion -> movement of molecules and ions out of peritubular capillaries into interstitial fluid into basolateral membrane of the tubular epithelial cells and into apical membrane into the lumen of the nephron tubule -> molecules that are both filtered and secreted are thus eliminated in the urine more rapidly than molecules that are not secreted •reabsorption = decrease in renal clearance •secretion = increase in renal clearance •excretion rate = (filtration rate + secretioin rate) - reabsorption rate if a substance in the plasma is filtered (enters bowman's capule) but is neither reabsorbed nor secreted its excretion rate must equal it filtration rate -> how we measure the glomerular filtration rate (GFR) tubular secretion of drugs •foreign molecules "xenobiotics" are eliminated more rapidly than would be possible by just glomerular filtration -> implies there are membrane carriers that recognize them as foreign Renal clearance of Inulin -> measurement of GFR •Inulin is a polymer of fructose produced by plants and is neight reabsorbed more secreted by the tubules letting us measure GFR •due to the high cost of inulin we often use creatinine and waste product of creatine which although is not reabsorbed has a slight amount secreted, however, this is small enough that its filtration lets us measure GFR as well

Vital Signs: Disappearing act

Daniel had a black blotch on his shoulder -> later diagnosed with an aggressive malignant melanoma (skin cancer) •through surgery the cancerous cells were removed -> two months later he noticed a lump in his armpit -> cancer had spread and he underwent chemotherapy cancer spread to his lungs and daniel began interferon-alpha therapy -> boosts the body's immune system response against tumors -> first round made him so sick he refused future treatments rapidly went downhill and was given radiation on localized spots such as his hips to reduce pain -> surprisingly he quickly felt better and after 3 months was looking healthier and had gained wait -> did a CT scan and found no cancer, only radiographic scars left by the cancer it was later found that he had a abscopal phenomenon -> caused by irradiation to one part of the body affects distant regions, although usually associated with radiotherapy it has been seen in other local cancer treatments such as cryotherapy and hyperthermia cancer that has been check by the immune system can reawaken such as in transplants where the donor organ has cancer dormant that becomes activated -> usually let the body reject the organ when possible cancer cells usually trick the immune system into thinking it is a normal cell, perhaps in abscopal phenomenon this is corrected so the body can attack the tumor •or perhaps T reg cells are activated •the goal is to find the cause so we can intentionally activate it in the future

Elasticity

Elasticity refers to the tendency of a structure to return to its intitial size after being distended -> made possibly by a high content of elastin proteins -> lungs are very elastic and resist distension •lungs are normally stuck to the chest wall -> stuck in a state of constant elastic tension -> increases during inspiration when the lungs are stretched and is reduced by elastic recoil during expiration

Clinical Application: Hypocapnia

Hypocapnia (low plasma Pco2) -> caused by hyperventilation -> leads to cerebral vasoconcstriction -> brain pefusion and hypoxia -> dizziness hypocapnia of hyperventilation also raises the blood pH "respiratory alkalosis) -> lowers plasma Ca++ -> results in neuromuscular irritability and muscle spasms (tetany) in the legs, feet, and hands symptoms can be alleviated by raising plasma Pco2 by breathing into a plastic back or tube with a large neutral space -> dangerous for those with asthma, angina, and myocardial infarctions

Formation of the placenta and amniotic sac

as the blastocyst implants in the endometrium and the chorion develops the cells of the endometrium also undergo changes -> cellular growth, accumulation of glycogen, overall changes are called decidual reaction -> due to maternal tissue being in contact with chorion frondosum called decidua basalis -> the chorion frondosum and decidua basalis (maternal tissue) together form the placenta "disc" cells of the cytotrophoblast from the chorionic villi invade the spiral arteries of the endometrium -> by end of second trimester the spiral arteries have been remodeled into dilated tube lined by the cytotrophoblast -> produce a low vascular resistance so that more maternal blood flows into the placenta the placenta is continous at its outer surface with smooth part of the chorion, which bulges into the uterine cavity •immediately beneath the chorionic membrane is the amnion -> the embryo, with umbilical cord is located within the fluid filled amniotic sac amniotic fluid is an isotonic secretion initially -> concentration changed later by urine from fetus -> also contains cells sloughed off from the fetus, placenta, and amniotic sac -> all have the same genetic composition allowing for detection of abnormalities in a procedure known as amniocentesis -> done at the 16th week of pregnancy when the amniotic sac contains between 175-225 mL of fluid -> disease such as down syndrome (chromosomal), Tay-sachs disease (myeline sheath degeneration) can be detedted major structural abnormalities cannot be predictable from genetic analysis but can be detected by ultrasound -> sound-wave vibrations are reflected from the interface of tissues with different densities such as the interface between the fetus and amniotic fluid to produce an image -> can see heart beat after a few weeks

Clinical application: amniocentesis

aspiration of a small amount of fluid containg fetal cells form amniotic sac -> performed at 14-20 weeks pregnant and fetus is at risk of genetic abnormalities samples obtained by amniocentesis can be analyzed by microscopic observation of the chromosomes "karyotyping" and biochemical analysis of DNA using chromosomal microarrays -> detection of abnormal number of chromosomes and genetic disorders such as sick-cell, tay-sachs, cystic fibrosis, and muscular dystrophy chorionic villus sampling (CVS) provides a larger number of fetal cells than amniocentesis anc can be perfomed as early as 10-12 weeks of pregnancy a mother's blood plasma contains a mixture of her DNA and DNA of the fetus -> some placental cells undergo apoptosis and release their DNA into teh blood which can be used as a noninvasive test for the fetal sex (SRY) and determination of the genome

Clinical investigation: Linda

Linda was given injections of GnRH to stimulate GnRH receptors in her anterior pituitary in a pulsatile fashion -> secretion of FSH and LH -> secretion of estradiol and progesterone from her ovaries took birth control pills containing estrogen and progesterone to compensate she may have uterine fibroids symptoms of painful menstruation, thinning hair, and growth of body hair are indicated PCOS -> ovarian cysts would have been seen in ultrasound to confirm this her physician advised Linda to lose weight and exercise due to the likelihood to develop type 2 diabetes otherwise due to PCOS risk factors her pregnancy test detected hCG a hormone secreted by embryonic trophoblast, using monoclonal antibodies against the beta subunit of hCG

Vital Signs: Save the Linebacker

Lineback had come to ER with airway problems, had gotten a cold a few days prior, but was having difficulty breathing now in a CT scan they could see a large mass in his upper chest -> lymphoma? a tumor originating from white blood cells his blood saturation level was dropping by the minute and his heart beat was becoming irregular -> oxygen saturation was down to 25% compared to 95-100 -> surgeon performed mouth to mouth and oxygen levels started to climb -> put him on a ventilator and his condition stabilized a pathologists was able to identify the tumor as a acute lymphoblastic leukemia -> the cancer had not spread and after after chemotherapy he started to quickly improve

Clinical application: Polycystic kidney disease (PKD)

PKD is a congenital disorder where the kidneys are enlarged by hundreds to thousands of cysts that form in teh nephron and eventually separate form the tubules autosomal dominant polycystic kidney disease(ADPKD) is the most common form 1:1000 people and is a dominant trait there is also a recessive gene version the mutation is on chromosome 16 that codes for a protein called polycystin-1, the other common mutation that occurs is on chromosome 4 that codes for polycystin-2 both of the genes produces in the cpithelial cells are important for the sensory function of the primary cilium -> primary cilium extends into the lumen of the renal tubules and serves as a mechanosensor -> when stimulated by flow of filtrate Ca++ is released -> acts as a second messenger for many cell functions no cure for the disease only treatments

Cleavage and blastocyst formation

at 30-3 hours after fertilization the zygote divides by mitosis "cleavage" -> into two smaller cells -> a second cleavage occurs 40 hours after fertilization -> four cells now -> a third at 50-60 hours -> ball of 8 cells is called a morula "mulberry" •this very early embryo enters the uterus approx. 3 days after ovulation has occurred -> cleavages 4-8 stage depend on RNA and proteins form the oocyte cytoplasm according to the embryo's gene continued cleavage produces a morula consisting of 32-64 cells by the 4th day -> while attached to uterin wall over the next two days it undergoes changes to become a hollow structure known as a blastocyst -> consists of two parts; the inner cell mass which will become the fetus, and the surrounding chorion, which will become the placenta (cells that form the chorion are known as trophoblast cells) on the 6th day following fertilization the blastocyst attaches to the uterine wall with the side containing the inner cell mass positioned against the endometrium -> the trophoblast cells produce enzymes that allow the blastocyts to penetrate the endometrium -> process of implantation "nidation" -> by 7-10th day the blastocyst is completely buried in endometrium •75% of lost pregnancies are due to failure of implantation and are rarely recognized as pregnancies

Pulmonary Disorders

People with pulmonary disorders frequently complain of dyspnea, a subjective feeling of "shortness of breath" •dyspnea may occur even when ventilation is normal, and may not occur when total minute volume (volume of one breath/breaths in a min) is very high, such as in exercise Asthma, characterized by dyspnea, wheezing and other symptoms are produced by obstruction of air flow through the bronchioles that occurs in episodes, or attacks •obstruction is caused by inflammation, mucus secretion, and bronchconstriction -> inflammation of airways is characterisitc of asthma itself contributes to increased airway responsiveness to agents that promote bronchiolar constriction -> bronchconstriction further increases airway resistance •increased airway resistance can be provoke by; allergic rxns in which IgE is produced, exercise (in individuals w/o asthama exercise can cause bronchconstriction w/ dehydration) breathing cold, dry air, and by aspirin (minority of asthmatics Atopic (allergic) asthma, is the most common form of asthma, and is a chronic inflammatory disorder of the airways characterized by hyper-responsiveness of airways to inhaled allergens -> activation of helper T cells -> release of cytokines -> IgE production and pulmonary eosinophilia (high # of eosinophils) when the person is again exposed to the same allergen, the allergen bonds to IgE on the surface of mast cells and basophils, causing these cells to release chemicals that promote inflammation -> histamine, leukotrienes, prostaglandins, and others that stimulate bronchoconstriction and mucous secretion of asthma •with repeated exposure to allergens -> sustained infiltration of eosinophils and basophils -> increased number of mast cells and goblet cells -> secretion of more mucus and increased bronchial smooth muscle mass -> accompanied by hyper-responsiveness to allergens and airway irritants early exposure to diverse microbes and their products can protect children against later asthma -> why asthma has increased in cities as children have been exposed to more "sterile" environments -> combined with air pollutants from traffic has lead to increased prevalence of asthma over the past few decades

Clinical investigation: Peter

Peter takes rescue inhaler -> contains ß-adrenergic receptor agonist such as albuterol -> bronchodilation also takes a long-acting ß-adrenergic receptor agonist and a glucocorticoid to reduce inflammation -> asthma is an obstructive lung disorder that would lower his FEV without his inhaler his cigarette smoking might have lowered his FEV got a pneumothorax from the knife wound -> elastic tension of the lung caused it to collapse -> physician suckedair from the pleural space -> intrapleural pressure again ell below his intrapulmonary pressure so that lung could expand peter appeared to develop acute mountain sickness when he went to 9,000 ft -> low Po2 caused cerebral vasodilation -> headache and nausea percent oxyhemoglobin was normal for that altitude -> was able to sufficiently oxygenate his blood

Active Immunity and the Clonal Selection Theory

Primary response After infection, it takes 5−10 days (latent period) before antibodies are detected in the blood. The person will get sick. •this sluggish primary response may not be sufficient to protect the person against the disease caused by the pathogen •antibody concentrations in the blood during this primary response reach a plateau in a few days and decline after a few weeks Secondary response Later exposure to the same infection results in maximum antibody production in less than 2 hours. The person will likely never get sick Clonal Selection theory •immunization procedures of Jenner and Pasteur were effective because those inoculated produced a secondary response rather than a primary, so rather than depending on an accumulation of antibodies it created a learning ability -> clonal selection theory -> accounts for most of the evidence why this occurs •B lymphocytes inherit the ability to produce certain antibodies, and T lymphocytes inherit the ability to respond to particular antigens •a given B lymphocytes can produce only one type of antibody with specificity for one antigen •this allows for some lymphocytes to respond to any disease even if it has never been seen in the body -> specificity of each lymphocyte is reflected in the antigen receptor proteins on the surface •exposure to an antigen stimulates division and production of identical cells "clones" -> some become plasma cells that secrete antibodies for primary response, while others become memory cells that can be stimulated to secrete antibodies during secondary response as well as living longer than naïve lymphocytes as well as activating easier (matter of hours to activate compared to days) long-lived memory T Cells are the most abundant lymphocytes in an adult •located in circulation and in lymphoid organs, and provide greater protection from pathogens •upon re-exposure to their specific antigens, memory cytotoxic T cells can quickly acquire the ability to kill infected cells with granzymes and perforins •memory T cells decline after 70 yrs -> increased susceptibility to infection secondary lymphoid organs, such as lymph nodes and spleen contain germinal centers •germinal centers develop from B cells that have been stimulated by antigens and activation by helper T cells -> B cells rapidly divides to become the founder of a germinal center that contains a clone of memory cells and plasma cells -> plasma cells within live longer •proliferating B cells in the germinal center undergo somatic hypermutation which generates a diversity of new antibodies -> can include antibodies that have a higher affinity for the stimulating antigen -> improved immune response

Renal function tests and kidney disease

Renal function can be tested by techniques that measure total blood for to kidneys and GFR by inulin clearance or plasma creatinine -> allow us to diagnosis diseases such as glomerulonephritis and renal insufficiency the urinary albumin excretion rate is a common test to detect excretion rate of blood albumin -> condition called microalbuminuria (30-300 mg protein/day) is often the first manifestation of renal damage from diabetes or hypertension •proteinuria -> present when person excretes more than 300 mg of protein per day -> 3.5 g a day occurs in nephrotic syndrome •diabetic kidney disease -> results ini proteinuria and progressive deterioration of kidney function and is the leading cause of end-stae renal disease (also seen in lupis) Acute Renal failure •ability of kidneys to excrete wastes and regulate homestasis of blood volume, pH, electrolytes detoriates over a short period of time -> rise in blood creatinin concentration and decrease in renal plasma clearance of creatinin -> possible result of reduced flow, atherosclerosis , or inflammation of renal tubules -> compromised function results from ischemia (reduced blood flow), or excessive use of certain drugs such as nonsteroidal antiinflammatory drugs (NSAIDs) such as phenacetin glomerulonephritis •inflammation of the glomeruli, of glomerulonephritis is believed to be an autoimmune disease -> involves a person's own antibodies -> go against the basement membrane of glomerular capillaries in response to streptococcus infections •variable number of glomeruli are destroyed in this condition and the reamaining glomeruli become more permeable to plasma proteins -> leakage of proteins into urin results in decreased plasma colloid osmotic pressure -> edema Renal insufficiency •nephrons are destroyed -> due to glomerullnephritis, infection of renal pelvis, pyelonephritis (nephron infection), loss of kidney, of damage caused by diabetes or kidney stones -> can lead to hypertension due to retention of salt and water and uremia (high plasma urea concentration) -> inability to excrete urea leads to high H+ concentration in plasma and elevated K+ concnetration -> can lead to uremic coma patients with uremia are placed on dialysis -> referring to the separation of molecules based on their ability to diffuse through an artifical selectively permeable membrane -> concept used in hemodialysis -> urea and other wastes in patient's blood can easily pass through membrane pores but plasma proteins are left behind •due to inability for the machine to reabsorb ions (Na+, K+, glucose) the substances are kept in the blood by including them in the dialysis fluid so their is no concentration gradient favoring their diffusion through the membrane, compared to bicarbonte concentration in dialysate is at first higher than in the blood favorint its diffusion into the blood •technique is performed 3x a week for several hours more cent techniques such as continuous ambulatory peritoneal dialysis (CAPD) use the patient's own peritoneal membrane •can be performed by the individual multiple times a day as a more convenient and less expensive method than hemodialysis -> less efficient at removing waste and is prone to infection the many dangers presented by renal insufficiency and the difficulties encountered in attempting to compensate for this condition are reminders of the importance in renal function in maintaining homeostasis

Restrictive and Obstructive disorders

Spirometry is useful in diagnosis of lung disease on the basis of pulmonary function tests, lung disorders can be classified as restrictive or obstructive •Restrictive -> such as pulmonary fibrosis, the vital capacity is reduced to below normal -> however the rate at which the vital capacity can be forcibly exhaled is normal •obstructive -> vital capacity is normal because lung tissue is not damaged such as in asthma -> expiration is more difficult and takes a longer time because bronchoconstriction increases resistance to air flow obstructive disorders are therefore diagnosed by tests that measure the rate of expiration •ex. forced expiratory volume (FEV) in which the % of vital capacity that can be exhaled in the first second (FEV1) is measured •and FEV1 that is significantly less than 80% suggests the presence of obstructive pulmonary disease

Clinical application: sudden infant death syndrome

Sudden Infant death syndrome (SIDS) -> unknown death of an infant under one also called "crib death" •evidence suggests it may be due to failure of the central or peripheral chemoreceptors to detect a rise in CO2 deaths have reduced significantly since putting babies to sleep on their backs and a firm surface, but still remains the leading cause of deaths of infants younger than one year

Thoracic Cavity

The Diaphragm is a dome-shaped sheet of striated muscle dividng the anterior body cavity into two parts 1. abdominopelvic cavity located below the diaphragm which contains the lvier, pancreas, gastrointestinal tract, spleen, genitourinary tract, and other organs 2. thoracic cavity -> located above the diaphragm contains the heart, large blood vessels, trachea, esophagus, and thymus in the central region (mediastinum) and is filled elsewhere by the right and left lung the lung-lateral to the mediastinum, are enveloped by two layers of wet epithelial membrane called the pleural membranes •the superficial layer, or parietal pleura lines the thoracic wall •the deep layer, or visceral pleura covers the surface of the lungs the lungs normally fill the thoracic cavity so that the visceral pleura covering each lung is pushed against the parietal pleura lining the thoracic wall -> results in little to no air between the visceral and parietal pleura •there is "potential space" or intrapleural space that can become a real space if the pleurae separate, such as we see in collapsed lungs

relationship between Na+, K+, and H+

The plasma K+ concentration indirectly affects the plasma H+ concentration (pH) -> change in plasma pH likewise affect the K+ concentration of the blood -> increase in H+ -> H+ moves into cells -> K+ diffuses outwared into extracellular fluid -> plasma concentration of H+ decreases while K+ increases -> reestablish the proper ratio of these ions in the extracellular fluid •similar effect in distal region of the nephron in cells of the late distal tubule and cortical collecting duct, positevely charged ions (K+ and H+) are secreted in response to the negative polarity produced by reabsorption of Na+ •there is also an apical membrane H+/K+ pump that pumps H+ into the filtrate in exchange for K+ which pumps from the filtrate into the cell -> pump is activated by acidoses -> results in secretion of H+ into filtrate and reabsoprtion of K+ -> by this effect acidosis is accompanied with a rise in blood K+ •alkalosis increases the renal secretion of K+ into the filtrate and into the urine •in hyperkalemia -> increased secretion of K+ and decreased secretion of H+ -> how hyperkalemia cna lead to acidosis because aldosterone promotes the secretion of both K+ and H+ into filtrate -> a high aldosterone secretion (ex. hyperaldosteronism "conn syndrome") causes both hypokalemia and metabolic alkalosis -> some of K+ loss may be minimized by ability of aldosterone to stimulate the H+/K+ pumps promoting K+ reabsorption •low aldosterone (ex. addison's disease) -> leads to hyperkalemia and metabolic acidoses

Intrapulonay and Intrapleural pressures

The visceral and parietal pleurae are stuck to each other like two wet pieces of glass. •the intrapleural space between them only contains a thin layer of fluid, secreted by parietal pleura -> fluid is formed as a filtrate from blood capillaries in the parietal pleura, and it is drained into lymphatic capillaries •major function of the liquid is to serve as a lubricant to prevent friction of lungs moving air enters the lung during inspiration due to the atmospheric pressure is greater than the intrapulmonary "intra-alveolar" pressure •intrapulmonary pressure must fall below atm pressure to cause inspiration -> pressure below that of atmospheric pressure is termed subatmospheric pressure or negative pressure atmospheric pressure and lung/chest pressure are measured using cmH2O •during quiet inspiration ~ -1 cmH20 -> the (-) refers to the pressure as sbatmospheric -> air enters the lungs during inspiration until the intrapulmonary pressure rises until reaching 0cmH20 (same as atmospheric pressure) •during expiration ~ +1 cmH20 -> air leaves the lungs until pressure falls until reaching the atmospheric pressure ( 0cmH2O) because of elastic tension of the lungs the thoracic wall on each othe -> pull in opposite directions •the elastic recoil of the lungs and chest wall produces a subatmospheric pressure in the intrapleural space of the two structures, this pressure is termed intrapleural pressure -> intrapleural pressure is lower (more negative) during inspiration due to expansion of thoracic cavity than it is during expiration -> although it is still lower than the intrapulmonary pressure during both inspiration and expiration The pressure difference across the wall of the lung, called transpulmonary "transmural" pressure -> difference between the intrapulmonary pressure and intrapleural pressure •because the pressure within the lungs is greater than outside the lungs the difference in pressure (transpumonary pressure) keeps the lungs against the chest wall •transpulmonary pressure is positive during both inspiration and expiration -> causing lungs to stick to the chest and producing changes in volume as the thoracic volume changes -> during inspiration, transpulmonary pressure causes the lungs to expand as the thoracic volume expands

Clinical investigation: Timmy

Timmy received booster vaccine for tetanus, diphtheria, and pertussis -> contained bacterial toxins that stimulate active immunity -> development of lymphocyte clones when timmy was cut by an old can he could have developed tetanusif he hadn't received this immunization -> cut did provoke inflammation -> release of histamine and other pro-inflammaotry cytokines -> blood vessel dilation, making would site swollen, with pain from prostaglandin E2 -> pus was produced by neutrophil release of proteases that liquefy tissues and by dead neutrophils cleansing of wound and application of bactericidal salve helped prevent infection from spreading and possibly causing systemwide inflammation known as sepsis timmy's season cough may be due to an immediate hypersensitivity reaction caused by IgE production and the release of histamine from mast cells and basophils -> histamine is a major mediator of the allergic symptoms of rhinitis, and so the antihistamine helped alleviate timmy's cough

Active and Passive Immunity

Vaccination first came about when rubbed needles into the pustules of people with mild forms of smallpox were injected into healthy individuals •later Edward Jenner used cowpox inoculations to build immunity against smallpox "vaccine" •Louis Pasteur found that when he heated anthrax bacteria their virulence, or ability to cause disease, was greatly reduced "attenuated" although their antigenicity, or nature to function as antigens was not significantly changed -> when this attenuated bacteria was injected, subsequent injections of active anthrax did not kill the individuals compared to those that had not been vaccinated there are four types of active (adaptive) immunity; 1. naturally acquired active immunity -> person is exposed by normal contact and is infected -> person produces antibody or specialized T-cells -> this type of immunity is long-lasting 2. Naturally acquired passive immunity -> natural transfer of humoral antibodies (mostly IgA, and a small amount of IgG) are also naturally passed in "colostrum" and mother's milk •this immunity lasts only for a few months (4-5) -> greatly reduces intestinal disease 3. artificially acquired active immunity -> a vaccine is administered to promote antibody production or confer immunity •relatively long-lasting 4. artificially acquired passive immunity -> transfer of humoral antibodies formed by one person (or animal) to a recipient who needs the antibodies (ex. antibodies against rattlesnake venom; or antivenin) •short-lived immunity (3-4 months) •concentrated gamma globulin obtained by process of serum protein electrophoresis can be injected into persons to increase humoral immunity before they travel to foreign countries (pooled fraction of IgG)

Urinary Buffers

When a person has a blood pH of less than 7.35 (acidosis) the urine pH almost always falls below 5.5 -> nephron cannot produce a urine pH less than 4.5 -> due to buffering by phosphates (HPO4) and ammonia (NH3) phosphate enters the urine by filtration, ammonia is produced by tubule cells by deamination of AA glutamine acidosis causes increased proximal tubule production of "extra" bicarbonate and ammonia from glutamine -> ammonia travels through the nephron loops and becomes concentrated in the interstitial fluid of the medulla -> creates a gradient favoring diffusion of ammonia into the collecting duct

Vital Sign: Where's that infection

Women had vomiting for many hours, total body pain, fever, and could barely walk had recently had a bladder infection -> given antibiotics -> pain returned later -> ran a test but she had no WBCs in urine -> pyelonephritis? but she didn't have a fever everything pointed to pyelitis "UI" -> put her on antibiotics -> infection entered her blood stream around the same time -> she quickly stabilized

Clinical application: hyperkalemia

a plasma K+ concentration greater than 3.5-5 mEq/L symptoms => nausea, weakness and changes in ECG aldosterone is required for the adequate elimination of K+ -> by stimulation of the secretion of K+ into the corical collecting ducts, and so adrenal insufficiency (seen in addison's disease) can cause hyperkalemia as well as hyponatreamia (low Na+) hypokalemia is anything below 3.5 mEq/L -> can lead to heart arrhythmias and muscle weakness -> commonly caused by use of certain diuretics, vomiting, and metabolic alkalosis but can also be caused by excessive aldosteron secretion by primary hyperaldosteronism (conn syndrome) or Cushing syndrome

Clinical Application: Pneumothorax

a pneumothorax ocurs when air enters the pleural space -> raise intrapleural pressure so that the pressure difference keeping the lung against the chest wall is abolished -> lung collapses due to elastic recoil a spontaneous pneumothorax may occur w/o disease or trauma -> caused by air leaking from the lung due to puncture from a broken rib or lung disorders such as COPD, cystic fibrosis, or a rupture of a lung blister an open chest wound can also allow air to enter the pleural space -> if it continues to enter w/o exit it produces a tension pneumothorax due to the lungs being separated a pneumothorax usually occurs in only one lung

Clinical Application: Pulse oximeter

a pulse oximeter noninvasively measures the oxyhemoglobin saturation -> has two light-emitting diodes (LEDs) •one emits red light (600-750nm) the other emits IR light (850-1000nm) -> oxyhemoglobin abosrbes relatively more IR light allowing mored red light to pass through the tissue to a sensor •deoxyhemoglobin absorbs more of the red and passes more of the IR light using this information the device determines the percent oxyhemoglobin saturation -> can be low if gas exchange has been compromised by impaired lung or heart function

oxyhemoglobin dissociation curve

blood in system arteries at a Po2 of 100 mmHg has a percent oxyhemoglobin saturation of 97% -> blood is delivered to the systemic capillaries where oxygen diffuses into the cells and is consumed in aerobic respiration (used as a terminal e- acceptor) •blood leaving the systemic veins is thus reduced in oxygen -> Po2 of 40 mmHg and the Percent oxyhemoglobin saturation is about 75% at rest (blood entering contains 20mL/100mL O2, when leaving it is 15.5mL/100mL) -> thus 4.5 mL of oxygen is loaded into tissues the graphic illustration of percent oxyhemoglobin saturation at different values is called a oxyhemoglobin dissociation curve •the large amount of oxyhemoglobin remaining in the venous blood serves as an oxygen reserve -> allowing you to stay alive 4-5 minutes without using cardiopulmonary resusciation techniques -> can also be used during increased demand during exercise the oxyhemoglobin dissociation curve is S-shaped "sigmoidal" -> the flat at high Po2 show the range where changes in Po2 don't make a sig. diffrane -> ex. to decrease oxyhemoglobin saturation of arterial blood from 97-93% you'd have to be as high as 10,000 ft •at the stepp part of the curve small differences in Po2 values make a large difference -> a decrease in venous Po2 from 40 mmHg to 30 mmHg that occurs during light exercise corresponds to a change in percent saturation from 75% to 58%, (the arterial Po2 is still 97% -> change occurs due to increased tissue demand) the difference between arterial and venous percent saturation indicates the percent unloading •in the preceding example, 97% - 75% = 22% unloading at rest, and 97% - 58% = 39% unloading during mild exercise -> during heavy exercise Po2 can drop as 20 mmHg or lower -> % unloading of 80% or more

Clinical application: carbon monoxide poisoning

carbon monoxide poisoning may be suspected when the blood carboxyhemoglobin is greater than 10% in smokers and 3% in nonsmokers CO poisoning is usually caused by burning of fossil fuels by faulty appliances or vehicles within an enclosed space symptoms include headache, weakness, dizziness, nausea, and confusion -> more severely can be neurological disturbances such as memory loss, psychiatric conditions, and cardiac injury treatment includes breathing 100% oxygen at 1 atm or breathing 100% oxygen at 1.4 atm in a hyperbaric chamber

Boyle's law

changes in intrapulmonary pressure occur as a result of changes in lung volume •Boyle's law states that the pressure of a given quantity of gas is inversely proportion to its volume -> an increase in lung volume results in a decrease in intrapulmonary pressure to subatmospheric levels -> gas enters •a decrease in lung volume -> raises intrapulmonary pressure above the atmosphere -> expels air from lungs

Effect of exercise and high altitude on respiratory function

changes in ventilation and oxygen delivery occur during exercise and during acclization to a high altitude -> help compensate for the icnreased metabolic rate during exercise and for the decreased arterial Po2 at high altitudes Ventilation during exercise -> breathing becomes deeper and more rapid to produce a total minute volume (volume of air expired in one breath by breaths/min) higher than resting value -> matched to a simultaneous increase in oxygen consumption and carbon dioxide production by exercising muscle -> arterial blood Po2, Pco2 and pH are held constant •possibly raises from CO2 production although not sure due to significant change in Pco2 between rest and exercise acclimizatization to high altitude -> changes in ventilation, hemoglobin affinity, hemoglobin concentration, chest size, and capillary density •ex. at 7,500 ft -> Po2 is 69 - 74 mmHg vs. 90-95 mmHg at sea level -> oxyhemoglobin saturation at this altitude is between 92-93% vs. 97% -> decrease in total oxygen content -> oxygen delivery to cell is reduced -> corresponds to fatigue at altitudes (even at 5-6,000 where oxyhemoglobin saturation is only slightly decreased) -> although accomodation occur in body the maximum oxygen consumption achieved during intense exercise decreases with altitude even when acclimatized Changes in ventilation start as low as 1,500 meters (5,000 ft) -> decreased Po2 stimulates carotid bodies to produce an increase in ventilation "hypoxic ventilatory response" -> hyperventilation -> lowers arterial Pco2 -> respiratory alkalosis -> blunts hypoxic ventilatory response -> done so by increasing arterial pH on peripheral chemoreceptors • net resulting in ventilation is high due to the hypoxic ventilatory response, but not as high as it would have been in the absence of respiratory alkalosis over a few days kidneys excrete bicarbonate in the urin producing a compensatory metabolic acidosis -> move pH of blood and CSF back to normal allowing hypoxic ventilator response to have more effect -> carotid bodies undergo a gradual increase in sensitivity to hypoxia increasing ventilation -> as a result a few days at high altitude changes total minute volume to 2.5 L/min higher than sea leel hikers climbing everest without supplemental oxygen had an average arterial Po2 of 24.6 mmHg at 28,000 ft and the average Pco2 was 13.3 mmHg vs. 40 mmHg at sea level -> hyperventilation at high altitude increases tidal volume reducing the contribution of air from anatomical dead space and increasing the proportion of fresh air to alveoli -> improves the oxygenation of the blood •hyperventilation cannot increase blood Po2 above that of inspired air hypoxia stimulates pulmonary vasconstriction -> with increased cardiac rate at high altitude -> raises pulmonary pressure •NO is produced in the lungs and for those at high altitude this promotes pulmonary vasodilation and blood flow -> lower pulmonary artery pressure and lower hematocrit of individuals born at high altitudes compared to those that are lowlanders ascending -> lower pulmonary artery pressure decreases the afterload of the right ventricle

chronic obstructive pulmonary disease (COPD)

characterized by chronic inflammation with narrowing of the airways and destruction of alveolar walls •included in this category is chronic obstructive bronchiolitis -> fibrosis and obstruction of the bronchioles, •emphysema is also a part of this category •this condition results in accelerated age-related decline in FEV1 asthama is also a chronic inflammatory disorder, but can usually be reversed through inhalation of a bronchodilator such as albuterol -> asthama is characterized by hyperresponsiveness, a abnormal bronchoconstrictor response to a stimulus •COPD is not triggered by allergies while asthma is •distinction between COPD and asthma can be complex especially when advanced asthma is not reversible -> due to airway remodeling bronchial hyperresponsiveness -> often seen in those with COPD as well primary difference between the two is the difference in cells involved in the inflammations •asthma -> helper T lymphocytes and eosinophils •COPD -> cytotoxic (CD8 cells) and neutrophiles about 90% of people with COPD are, or have been smokers •genetic susceptibility is also a factor, however 10-20% of smokers have it -> smoking has many free radicals that recruit macrophages and neutrophils -> release protein-digesting enzymes that together with reactive O2 species promote lung damage seen in emphysema •cigarette smoking also stimulates proliferation of mucus-secreting goblet cells of the respiratory tract, and excessive mucus production correlates with COPD severity •cigarette smoking promoters remodeling of airways -> contributing airflow obstruction, and remodeling of blood vessels -> pulmonary hypertension •smoking also is a preventable cause of lung cancer -> cancer responsible for the most deaths worldwide the majority of thoe with COPD are smokers -> once COPD has begun to form progression cannot be stopped, even by quiting smoking •inhald corticosteroids can be used to treat COPD in a limited fashion •COPD can lead to a variety of issues -> pneumonia, pulmonary emboli, heart failure, cor pulmonale "pulmonary hypertension" -> leads to hypertrophy and failure of right ventricle •COPD is the 5th leading cause of death worldwide, and estimated to increase to 3rd

Clinical application: Physiological jaundice of the newborn

characterized by yellowing of the skin, sclera, and mucous membranes that commonly occurs in newborns at about 2-4 days of age and lasts 2 weeks the yellowing is caused by the pigment bilirubin, produced from heme derived from the hemoglobin of destroyed RBCs -> elevated in newborn because fetal RBCs containing hemoglobin F have a shorter life span than adult RBCs containing hemoglobin A in the fetus, bilirubin passes through the placenta because it is lipid-soluble, but after birth it must be converted by the liver into a water-soluble form known as conjugated bilirubin so that it can be excreted in the bile -> takes time to produce the needed enzyme usually not dangerous, but if concerns arise the baby can undergo phototherapy that converts the unconjugated bilirubin into a water-soluble derivative that can be excreted

Effects of Blood Pco2 and pH on ventilation

chemoreceptor input to the brain stem modifies the rate and depth of breathing so that under normal conditions the arterial Pco2 pH, and Po2 remain constant •in hypoventilation (inadequate ventilation) -> Pco2 rises and pH falls (acidic) -> fall in pH occurs as CO2 combines with H2O to form carbonic acid releasing H+ into the solution (CO2 + H2O -> H2CO3 -> H2CO2 -> H+ + HCO3-) •the oxygen content of blood decreases more slowly than CO2 increases during hypoventilation because the large reservoir of oxygen attached to hemoglobin during hyperventilation -> blood Pco2 quickly falls and pH rises (more alkaline) because of the greater elimination of carbon dioxide and carbonic acid •oxygen content of blood, on the other hand, is not significantly increased by hyperventilation (because hemoglobin is saturated with oxygen even during normal ventilation) for these reasons blood Pco2 and pH are more immediately affected by changes in ventilation than is the oxygen content -> changes in Pco2 provide a sensitive index of ventilation -> therefore ventilation is adjusted to maintain a constant Pco2, and proper oxygenation is a side product of this reflex during birth the umbilical cord is clamped -> buildup of CO2 => fall in pH -> stimulates peripheral chemoreceptors -> first breath •when first born babies mainly use their diaphragm to breath as their intercostal muscles are not yet developed, also babies are primarily nose breathers for the first two months of their life the rate and depth of ventilation are normally adjusted to maintain an arterial Pco2 of 40 mmHg •hypoventilation -> rise in Pco2 "hypercapnia" •hyperventilation -> lack in Pco2 "hypocapnia" hyperventilation can lead to shallow water blackout and death •swimmer hyperventilates to allow them to swim longer -> blow off CO2 -> pH rises due to lowering free H+ -> respiratory alkalosis -> reduced stimulus for breathing -> dives and vigourously swims reducing O2 levels in blood -> insufficient aerobic metabolism -> lack of ATP produced in brain -> unconsciousness, and drowning

Active Immunity

development of a secondary response provides active immunity against the specific pathogens -> the sluggishness of the primary response may cause the person to develop the disease -> why children who get measles, chicken pox, etc. Clinical immunization programs induce primary responses with attenuated or destroyed, or closely related strains or microorganisms that are antigenically similar but less pathogenic (ex. cowpox -> where "vaccination" comes from) •inoculation with cow pox virus conferred "cross-reactive immunity" in those later exposed to smallpox -> same concept we see when strep bacteria lead to an autoimmune response •all these procedures lead to development of lymphocyte clones that can combat virulent pathogens by producing secondary responses •the first polio vaccine (salk vaccine) was composed of viruses that had been inactivated with formaldehyde which were then injected into the body -> this is the most used vaccine in the US •the later devloped oral vacccine contained living virues that have attenuated virulence -> viruses invade the epithelial lining of the intestine and multiply but don't invade nerve tissue -> in rare cases this became polio disease in those with weakened immune systems •by using vaccines the immune system can become sensitized to polio antigens and produce a secondary response if polio viruses are later enountered therefore there are three ways vaccines are produced. vaccines may use •live viruses -> attenuated virulence that do not cause disease but provoke strong immune response against the virulent viruses (ex. sabin oral polio vaccine, measles, and mumps •killed virulent virus -> do not cause the disease (ex. Salk injected polio vaccine) •recombinant viral proteins -> produced through genetic engineering and given by themselves (ex. hepatitis B vaccine, from yeast, and attempted HIV vaccines) immunizations improved after the 1920s as adjuvants were added, improving immune response when delivered with vaccine antigens •adjuvants are pathogen-associated molecular patterns "PAMPs" -> enhance the adaptive immune response by boosting the ability of antigen presenting cells to activate B and T lymphocyte responses •in dendritic cell secretion of IL-2 and IL-12 are stimulated -> enhance B cell secretion of antibodies •when they stimulate the dentritic cell release of IL-4, and IL-6 they stimulate the T cell-mediate response •adjuvant benfits occur because of dendritic cell pattern-recognition receptors that bind PAMPs and damage associated molecular patterns "DAMPs" -> these reactions help determine the nature and effectiveness of the adaptive immune response and effectiveness of a vaccination

Vital signs: guidelines released to reduce C-sections

drs. should give women more time to deliver, and C-sections should be seen only as a last resort or when absolutely needed •epiduals can slow labor the latent phase was previously considered to be dangerously stalled if longer than 14-20 hours, however this is now considered a latent phase and not a worry if it takes longer active labor doesn't occur until the cervix is dilated 6 cm, not 4 cm as thought in the past forceps can offer a safer alternative to cesareans

lactation

each mammary gland is composed of 7-10 lobes divided by adipose tissue -> adipose tissue determines size and shape of breast but has nothing to do with nursing ability -> glandular and fibrous tissues varies and determines the density of breasts in mammograms -> each lobe is subdivided into lobules which contain a glandular alveoli that secrete the milk of a lactating female clustered alveoli secrete milk into a series of secondary tubules - converge to form mammary ducts -> converge to form lactiferous duct that drains at the tip of nipple •lumen of each lactiferous duct expands just beneath the surface of the nipple to form an ampulla (lactiferous sinus) where milk accumulates during nursing •epithelial cells that line the tubules and those that form the alveoli secrete water and nutrients for lactating mammary galnds •specialized myoepithelial cells can contract to prople milk through system of ducts mammary glands become secretory durng early pregnancy by hormone including estrogen, progesterone, and prolactin •following parturition the secretion of milk requires these hormones to work together hormes that regulate metabolism (insulin, cortisol, and thyroid) •prolactin secreted by anterior pituitary is important for the stimulation of milk production after parturition -> once lactation is establish the sucking of infants acts to stimulate milk production prolactin secretion is controlled by prolactin-inhibiting hormone (PIH) -> identified as dopamine released into the hypothalamo-hypophyseal portal system of vessels -> secretion is inhibited by estrogen which when high during pregnancy -> prolactin increases from 20-40 ng/mL at end of first trimester to 100-400ng/mL at term -> begins to stimulate some milk production by mammary glands during pregnancy •high levels of progesterone and estrogen during pregnancy inhibit the ability of prolactin to stimulate mammary glands until after parturition when progesterone and estrogen levels fall -> some women lactate colostrum during pregnancy afterparturition -> placenta expelled -> declining levels of hormones -> milk production • women who don't want to breast feed can take bromocriptine -> binds to dopamine receptors and promotes action of dopamine as PIH act of nursing helps maintain high levels of prolactin secretion via a neuroendocrine reflex -> sensory endsin breast relay impulse to hypothalamus to inhibit PIH secretion •suckling also results in secretion of oxytocin form posterior pituitary -> made in hypothalamus and stored in posterior pituitary -> milk-ejection reflex "milk letdown" -> occurs as oxytocin stimulates contraction of myoepithelial cells surrounding the lactiferous ducts •milk letdown can be a conditioned response to visual or auditory cues or can be repressed in fight-or-flight situations breast milk contains many nutrients and proteins such as casein and lactalbumin, lipids, carbs, B vitamin, Vitamins A, D, E, and ions as well as IgA and IgG -> breast fed babies have reduced risk for a variety of maladies -> recommended babies be breastfed for first 6 months minimum breastfeeding supplements the immune protection given to the infant by its mother •while in utero the placenta allows for IgG -> provide protection for first 3 months after birth -> IgA from colostrum serves as passive immunity for teh baby from a variety of infections and allergies breast-feeding acting through reflex inhibition of GnRH can also inhibit secretion of gonadoptropins from the mother's anterior pituitary and thus inhibit ovulation •breast feeding is thus a natural contraceptive mechanism that helps to space briths -> particularly in women with limited caloric intake and for those that breastfeed at frequent intervals •not as effective in well-nourished women that breastfeed at more widely spaced intervals

Disorders caused by high partial pressure of gases

for every 33 ft (10 m) below sea level we see an increase in 1 atmosphere (760mmHg) -> a diver goes down 10 m when the partial pressure and amount of dissolved gases in plasma will be twice the values at sea level -> at 20 m 3x, at 30 m 4x oxygen toxicity •breathing 100% O2 at 1 or 2 atm can be safely tolerated for a few hours, higher Po2 can be dangerous -> develops rapidly over 2.5 atm -> oxidation of enzymes and other destructive changes that can damage the nervous system and lead to coma and death -> why divers use gas mixtures for deep levels nitrogen narcosis (oxxurs when a person is at depth) •at sea level N2 is inert -> under hyperbaric (high pressure) dissolved ntirogen can have deleterious effects -> due to nitrogen in plasma membranes •symptoms resemble alcohol intoxication "rapture of the deep" -> severity depends on depth -> dizziness and extreme drowsiness are other effects decompression sickness •upon ascending to sea level N2 dissolved in plasma decreases due to decrease in Pn2 -> expelled through breath •is ascent is too rapid bubbles of N2 gas can form in the tissue fluids and blood creating gas emboli (seen often in the base of the spinal cord) -> think of this in the way soda CO2 gas escapes upon opening the bottle •bubbles of N2 gas block small channels -> muscle & joint pain as well as more serious damage -> process known as decompression sickness "bends" (due to body contortion) •airplains that fly long distances at high altitudes have pressurized cabins so that passengers don't feel the low atm -> if cabin were to become rapidly depressurized at high altitude we would see a similar effect to Bends as seen in Aloha Flight Airlines #243

Surface Tension

forces that act to resist distension include elastic resistance and the surface tension exerted by fluid in the alveoli •luns both secrete and abosrb fluid in two antagonistic processes that leave only a thin film of fluid on the avleoli •fluid absorption is driven through osmosis, by the active transport of Na+ •fluid secretion is driven by active transport of Cl- out of the alveolar epithelial cells •individuals with cystic fibrosis have a defect in the CFTR (cystic fibrosis transmembrane conductance) gene resulting in a defective Cl- carrier -> results in an imabalance of absorption/secretion so that airway becomes very viscous (with lower water content) and is difficult to clear The thin film of fluid normally present in the alveolus has a surfae tension produced by water molecules atthe surface attracted more to other water molcules rather than air -> results in preventing the alveoli from collapsing on exhaling and helps to violate law of laplace surface tension acts to collapse the alveolus, and in the process increases the pressure of the air within the alveolus, as described in the law of laplace, pressure thus created is directly proportional to the surface tension and inversely proportional to the radius of the alveolus •theoretically the small the alveolus the greater the surface tension -> would cause smaller alveolus to empty into larger alveolus -> prevented due to as alveolus decrease in size the surface tension (equation numerator) is decreased at the same rate the radius (denominator) is reduced

Structure of the Respiratory System

gas exchange in the lungs occurs across 300,000,000 100µm air sacs known as pulmonary alveoli -> provides a SA of 60-80 square meters or 760 square ft for gas diffusion •diffusion rate betwen alveolar air and capillary blood depends on the distance between them -> average thickness of an alveolar cell and capillary endothelial cells is .15µm -> air-blood distance is ~.3µm there are tow types of alveolar cells designated type I alveolar cells and type II alveolar cells •type I alveolar cells -> 95-97% of total SA of lungs -> gas exchang with blood primarily takes place through these cells -> they are very thin, with the basement membrane and capillary cells being as little as .3µm •type II alvevolar cells -> secrete pulmonary surfactant and reabsorb Na+ and H2O preventing fluid buildup in the lungs in order to maximize gas diffusion the air-blood barrier is very thin •however alveolar wall is not fragile and can withstand the high stress of excercise and lung inflation •the great tensile strength os the wall is proided by the fused basement membranes composed of type IV collagen proteins of the blood capillaries and alveolar walls alveoli are polyhedral in shape and clustered in a honeycomb like state •air within one member of the cluster can enter the rest through small pores -> these small clusters occur at the ends of respiratory bronchioles, thin air tubes that end blindly in alveolar sacs -> individual alveoli can also occur along the tube •although the distance between each respiratory bronchiole and its terminal alveoli is only about .5µm these units together constitute most of the mass of the lungs air passages of the respiratory system are divided into two functional zones 1. respiratory zone -> region where gas exchange occurs, and it therefore includes the respiratory bronchioles, which contain individual alveoli along the tub, as well as alveolar sacs 2. conducting zone -> includes all the anatomical structures through which air pases before reaching the respiratory zone air enters the respiratory bronchioles from terminal bronchioles which are the narrowest airways w/o alveoli and don't contribute to gas exchange •receive air from larger airwars formed by branchings of right and left primary bronchi -> these air passages are continuous with the trachea "windpipe" located in the neck in front of the esophagus •the trachea is a sturdy tube supported by C-shaped rings of cartilage -> up to 23 division of branching tubes from the trachea to the alveoli (lead to the term respiratory tree, where the trunk is the trachea)

Reabsorption of glucose

glucose and AA in the blood are easily filtered by the glomeruli into the renal tubules -> not present above trace amounts in urine -> completely reabsorbed -> occurs in proximal tubule by secondary active transport mediated by cotransport of glucose and Na+ -> displays property of saturation "transport maximum (Tm)" (seen in present of glucose in diabetic urine) •the average Tm for glucose is 375 mg/min -> much higher than it is typically delivered •rate of glucose filtration = plasma glucose concentration x GFR •if fasting glucose concentration is 1mg/mL and the GFr is 125 mL/min -> rate of GFR is about 125 mg/min -> carriers are saturated at 375 mg/min (triple the average) Glycosuria -> presence of glucose in urine -> when plasma glucose concentration reaches 180-200 mg/100mL •although considered still in average zone -> nephrons likely have lower Tm values than average if we see glycosuria the reanl plasma threshold is the minimum plasma concentration of a substance that results in the excretion of the substance in urine (190 mg/100mL of blood) -> glucose is normally below with a fasting value aroud 100 mg/100mL and not typically exceeding 150 mg/100mL •glycosuria occurs when plasma glucose concentration is abnormally high "hyperglycemia" and exceeds the renal plasma threshold fasting hyperglycemia is caused by inadequate secretion of insulin -> an individual with this condition will has osmotic diuresis due to the higher mOsm caused by excretion of glucose drawing water out

Increased hemoglobin and red blood cell production

hemoglobin concentration risse within a day or two of ascent to a high altitude due to dehydration and reduced plasma volume caused by hyperventilation of dry air -> kidneys secrete erythropoietin -> stimulates bone marrow to increase production of hemoglobin and RBCs (ex. those at high altitude can have 19.8 g /100 mL vs. 15 g at sea level) •although percent oxyhemoglobin saturation is lower than at sea level the total oxygen content of the blood is greater -> 22.4 vs. 20 mL/100mL increased RBC and hemoglobin concentration at high altitude are not unalloyed benefits -> polycythemia increases the blood viscosity -> increasing vascular resistance -> pulmonary hypertension -> edema & right ventricular hypertrophy -> heart failure • in pregnant women polycythemia can increase fetal mortality the ideal hemoglobin concentration is close to 18g/dL of blood -> 21-23g/dL and above circulation becomes abnormal and person displays signs of chronic mountain sickness •fetus attains hemoglobin concentrations close to 18g/dL before birth when oxygen levels are low -> concentrations drop rapidly after birth when blood oxygenation rises during first breath notes on other acclimizations •increased in chest dimensions in those that live at higher altitudes -> more air enters •increase in number of capillaries ->improved movement of gases

Inherited defects in hemoglobin structure and function

hemoglobin diseases are normally produced by congenital (inherited) defects in the protein part of hemoglobin Sickle-cell anemia •in 8-11% of those of african descent, is a recessive state disease making it the most common monogenic (single gene) disorder and is an inherited hemoglobinopathy •occurs when a person inherits the affect gene from both parents which produces hemoglobin S compared to the A form -> differs at one AA were a valine is substituted for a glutamic acid in the beta chains of hemoglobin due to point mutation under conditions of low Po2, when hemoglobin is deoxygenated, hemoglobin S polymerizes into long fibers -> gives sickle shape reducing their flexibility and ability to pass through narrow vessels -> leads to infarctions •fibers also damage the membrane of RBCs and promote hemolysis an dhemolytic anemia reducing life expectancy •treated with hydroxyurea which stimulates the production of hemoglobin gamma chains instead of beta chains -> production of fetal hemoglobin rather than S form • can also recieve bone marrow transplants -> large risk but has resulted in curing the disease in some cases Thalassemia -> any of the family of hemoglobin diseases found amongst the mediterranean people some types of abnormal hemoglobins have been shown to be advantageous in the environments they evolved from -> sick-cell anemia offers resistance to malaria -> parasite in this disease cannot survive

Clinical application: Humanized monoclonal antibodies

humanized monoclonal antibodies for cancer treatments are antibodies against against tumor antigens that are bioengineered chimeric (genetically different parts) mouse/human models •grown in mice, but portion that binds to antigens is grafted onto human antibodies •examples include rituximab (for non-hodgkin's lymphoma, leukemia, and others) trastuzumab (treatment of HER2/neureceptor-positive breast cancer), and bevacizumab for treatment of colorectal, lung, and other cancers adoptive cel transfer therapies for cancer involve harvesting a patients T cells and using them to combat the patients cancer •ex. melanoma generates T cells specific for the cancer's antigens -> these can be harvested and stimulated to prolifeate in vitro by IL-2 and put back into the tumor area -> to prevent suppression by T reg cells the patient undergoes radiation and chemotherapy, this overall results in tumor-infiltrating lymphocyte (TIL) chimeric antigen recpeptor (CAR) therapy involves chimeric T cell receptors with specificity for tumor antigens that are given to the patients T cells in vitro -> very effective against acute lympoblastic leukemia in clinical trials and is FDA approved immune checkpoint blockade therapy invovles the administration of antibodies against certain cytokines that inhibit cytotoxic T cell function -> blocking this checkpoint allows for attack on tumor by T cells scientists are also attempting to produce vaccines against tumors, and unique tumor antigens •antigens can be mutated DNA of tumor cells, viral DNA (cervical cancer and Hodgkin's lymphoma) -> called neoantigens due to not being present in the fetus for development of tolerance stages through clonal deletion and anergy •neoantigens should thus be targeted by immune system

Implantation of the blastocyst and formation of the placent

if fertilization does not take place the corpus luteum begins to decrease secretion of steroids about 10 days after ovulation -> causes sloughing of endometrium following day 28 of cycle -> prevented in instance of fertilization chorionic gonadotropin -> blastocyst saves itself form being eliminated with the endometrium by secreting chorionic gonadotropin "hCG" (h=human) -> identical to LH in effects allowing for mainting corpus luteum past time -> secretion of estradiol and progesteron is maintained and menstruation is prevented secretion of hCG declines by 10th week of pregnancy -> although only required for first 5-6 weeks due to placenta itself becoming an active steroid hormone secreting gland -> by the 5th week the corpus luteum begins to regress

Immune Complex Diseases

immune complexes refer to antigen-antibody combinations that are free rather than attached to bacterial or other cells •formation of these complexes -> activation of complement proteins and promotes inflammation •self-limiting inflammation, due to removal by phagocytic cells •when present in large amounts, immune complexes can lead to prolonged inflammation -> can create widespread inflammation and organ damage when these complexes travel termed "immune complex disease" immune complex diseases result from infections by bacteria, parasites, and viruses •ex. hepatitis B, widespread inflammation of arteries caused by immune complexes made up of viral antigens and antibodies is termed periarteritis -> arterial damage is not caused by the hepatitis virus but rather the inflammatory process •immune complexes can also result from complexes between self-antigens and autoantibodies producing systemic autoimmune disease where inflammation and tissue damage is widespread in rheumatoid arthritis, there is inflammation of the synovial membranes and fluid of peripheral joints that cause damage to joints -> likely caused by infiltration of synovial membranes by helper T cells -> secrete pro-inflammatory cytokines leading to activation of B cells, resulting in autoantibodies -> these antibodies including rheumatoid factors-IgM antibodies bind to the Fconstant portion of IgG antibodies creating immune complexes activating complement proteins -> this extends inflammation, attracting and activating phagocytic polymorphonuclear leukocytes •rheumatoid arthritis affects joints symmetrically on both sides of the body and can have systemic symptoms of fatigue, anorexia, and wekaness • in addition to rheumatoid factor (RF) there are other autoantibodies that target modified proteins in the inflamed joints -> modification involves PTMs of the AA arginine into the AA citrulline -> these modified proteins can be tested using cyclic cirtrullinated peptide (CCP) assay,-> more specific than testing for RF and is the major test in diagnosis of rheumatoid arthritis systemic lupus erythematosus (SLE), is a systemic autoimmune disease involving the kidneys, joints, skin, CNS, and other body structures -> the affected people, 90% of which are women produce a wide range of autoantibodies •the unique factor is the production of IgG antibodies against their own nuclear constituents (antinuclear antibodies "ANA") -> antibodies target chromatin and snRNPs •cells undergoing apoptosis release these components on a regular basis -> in SLE they lose tolerance to these self-antigens -> binding of nuclear antigens to autoantibodies can form immune complexes throughout the body, provoking inflammation that can damage organs -> such as the case of damage to glomerular capillaries producing glomerulonephritis •multiple genetic factors can contribute to SLE, but environmental factors are the most important (ex. UV light) •treatment includes antimalarial drugs (inhibit toll-like receptors, which promote autoimmunity) and various anti-inflammatory and immunosuppressive drugs

effect of pH and temperature on oxygen transport

in addition to changes in Po2, the loading and unloading reactions are influenced by changes in the affinity (bond strength) of hemoglobin for oxygen -> weaker bond to oxyhemoglobin in blood passing exercising muscles due to lower pH and increased temperature The affinity is decreased as the pH is lowerd and increased as pH is raised -> Bohr effect •affinity of hemoglobin for oxygen is reduced -> slightly less loading of the blood with oxygen in the lungs but greater unloading of oxygen in the tissues -> net effect of tissues receiving more oxygen when blood pH is lowered •pH can be decreased by CO2 -> the Bohr effect helps provide more oxygen to the tissues when the CO2 output is increased by faster metabolism •on dissociation curve we see a shift to the right by lowering pH and a shift to the left by a rise in pH -> to the right is greater unloading and the reverse to the left when oxyhemoglobin dissociation curves are constructed on different temperatures the curve moves rightward as the temperature increases -> warmed exercising muscles receive increased delivery of O2

Delayed Hypersensitivity

in delayed hypersensitivity, symptoms take longer to develop than immediate hypersensitivity -> due to being mediated by a cell-mediated T cell response rather than antibodies •symptoms are caused by lymphokine secretion rather than histamine -> treatment with antihistamines provide no benefit -> use of corticosteroids are used for treatment allergic contact dermatitis, caused by poison ivy, poison oak, and poison sumac are classic examples •skin tests for TB, the tine test and Mantoux test "purified protein derivative (PPD) test" rely on delayed hypersensitivity reactions -> if a person has been exposed to tubercle bacillus they have consequently produced T cell clones -> skin reactions appear within days of tubercle antigens rubbed into the skin with small needles (tine test) or are injected under the skin (Mantoux test) in allergic contact dermatitis, a person can develop an inflammatory skin rash in response to cosmetics, jewelry, and other products that touch the skin •small molecules in these products penetrate the skin and bind to self-proteins creating a new antigen in a haptenization process -> new antigen stimulates a T cell response and leads to allergic rash -> why Andy can't wear stainless steel (wristwatches) and dresses as he does to carry a pocket watch

countercurrent multiplier system

in order for water to reabosrbed by osmosis the surrounding insterstitial fluid must be made hypertonic -> the renal medulla can be up to 4x the mOsm than the plasma by juxtamedullary nephrons -> shape of loops contribute to this Ascending limb of the loop of henle •separated into two regions; the thin segment near the tip of the loop, and the thick segment which carries the filtrate into the distal convoluted rubule in the renal cortex -> the thick segment actively extrudes 20-25% of the filtered salt from the lumen into interstitial fluid -> accomplished by the Na+-K+-2Cl- cotransporter -> the passive movement of Na+ down the electrochemical gradient drives the inward secondary active transport of K+ and Cl- in the same direction in the ratio the name implies -> Na+ is then actively transported across the basolateral membrane to the interstitial fluid by the Na+/K+ pumps -> followed by Cl- as described, and K+ passively diffuses back into the filtrate •although different than in the proximal tubule the net effect is the same with slat being extruded -> however, the asscening limb of the loop of henle is not permeable to water -> increasingly dilute as ions leave and interstitial fluid surrounding the nephron becomes increasingly more concentrated -> tubular fluid that enters the distal tubule is made hypotonic (100 mOsm) where the interstitial fluid is made hypertonic Descending limp of the loop •deeper regions of the medulla around the tips of the loops of juxtamedullary nephrons reach concentrations of 1,200 mOsm -> caused due salt becoming trapped in insterstitial fluid •the descending limb is impermeable to passive diffusion of salt, but is permeable to water -> water is drawn out by osmosis and enters blood capillaries -> increase in concentration of tubular fluid and loss of volume -> at the base of the descending loop the fluid as the same mOsm as the interstitial fluid of 1,200 mOsm -> multiples the concentration of salt take in the ascending loop

Exchange of molecules across the placenta

in order to supply sufficient blood to the placenta, and sufficient O2 and nutrient to the fetus changes must be made -> blood volume of mother increases by 40%, and her total peripheral resistance decreases due to arteriolar vasodilation •maternal blood is delivered to and drained from teh cavities within the decidua basalis located between the chorionic villi • two umbilical arteries deliver fetal blood to vessels within the chorionic villi and one umbilical vein drains the blood from the villi back to the fetus • due to placenta structure only two cell layers separate molecules in the maternal blood from fetal blood -> serve as site of exchange of gases and other molecules (O2 and CO2, and waste products) placenta also has a high metabolic rate using 1/3 of oxygen and glucose supplied by maternal blood -> rate of protein synthesis is higher in the placenta than in the liver -> placenta delivers a vareity of enzymes capable fo converting hormones and exogenous drugs into less active molecules -> prevents dangerous molecules from harming the fetus •alcohol can still cross -> cause fetal alcohol syndrome •cocaine, marijuana, methamphetamine, and other drugs can cross and cause fetal damage

Innate lymphoid cells

innate lymphoid cells (ILCs) -> part of innate immune system, however unlike lymphocytes of the adaptive immune system innate lymphoid cells do not have receptors for specific antigens, and don't respond in a specific way to antigens •respond to signals from infected or injured tissues as part of the innate immune system •two subclasses -> noncytotoxic helper cells and natural killer (NK) cells noncytotoxic innate helper lymphoid cells •equivalent to the helper T cells of the adaptive immune system •in response to infections and tissue damage -> secrete various cytokines promoting an immune response •prominent in the intestine and other mucosal barriers -> shape immune response against pathogens such as viruses, bacteria, and fungi in a critical spot natural killer (NK) cells •ILCs analogous to the cytotoxic T cells of the adaptive immune system -> lack receptor diversity generated by gene rearrangements to provide receptors for specific antigens •inherit receptors that allow them to target malignant cells (cancers) and cells infected with intracellular pathogens (viruses) •have receptors that interact with class-1 MHC molecules on the person's own cells -> provides tolerance to the person's self-antigens and preventing autoimmune attack •have the ability to restrain the production of tumors, which led to their discovery in an experiment in mice that lacked a thymus gland and T cells •resting NK cells release cytokines (interferon-y & others) as well as intracellular granules with granzymes and perforin -> allows for cells to kill by contact, but without prior exposure to foreign antigens -> to be effective they must first be activated by interferon-a, interferon-ß, and other pro-inflammatory cytokines •the released interferon-y and other cytokines activate macrophages and cells of the adaptive immune system -> do to not requireding prior exposure to antigens they serve as the first line of innate, cell-mediated defense, later backed by cytotoxic T cells NK cells like the cells of the adaptive immune system can produce long lasting memory cells -> mounts a stronger secondary response -> therefore these cells have characteristics of both the innate and adaptive systems •the discovery of natural killer T cells (NKT cells) is a type of T cell which respond to lipid antigens and have both innate and adaptive characteristic

Regulation of breathing

inspiration and expiration are produced by the contraction and relaxation of skeletal muscles in response to activity in somatic motor neurons in the spinal cord -> controlled by respiratory control centers in the medulla oblongata (pons) and from neurons in the cerebal cortex Brain stem respiratory centers •respiratory rhythm is generated by a loose aggregation of neurons in the ventrolateral region of the medulla oblongata -> forms rhythmicity center -> influenced by two control centers in the pons •apneustic center -> promote inspiration by stimulating the inspiratory neurons in the medulla •pneumotaxic center -> antagonizes the apneustic center and inhibit inspiration chemoreceptors •automatic control of breathing is also influenced by chemoreceptors -> sensitive to the pH change of brain interstitial fluid and cerebrospinal fluid, and the Pco2 pH and Po2 of the blood •two groups of chemoreceptors, central in the medulla oblongata and peripheral •peripheral chemoreceptors -> contained within small nodules in the aorta and carotid arteries -> include the aortic bodies located in the aortic arch, and the carotid bodies located in each common carotid artery at the branch point (*no the same location as aortic and carotid sinuses which measure blood pressure) •peripheral chemoreceptors control breathing indirectly via sensory nerve fibers to the medulla -> aortic bodies send sensory info to the medulla in the vagus nerve (X), while carotid bodies stimulate sensory fibers in the glossopharyngeal nerve (IX)

Reabsorption of Salt and Water

kidneys only excrete 1-2 L of urine in a 24hr period (only 1% of body volume) •varies from 16 mL a minute if drinking a lot, to .3 mL/min in severe dehydration -> 400 mL excreted -> minimum needed to excrete the metabolic wastes produced by the body "obligatory water loss" -> above this the urine becomes increasingly dilute return of filtered molecules from the tubules to blood is known as reabsorption -> about 85% of 180 L of glomerular filtrate formed is reabsorbed in a constant, unregulated fashion by proximal tubules and descending loops -> remaining occurs by oxmosis caused by a concentration gradient between the tubular filtrate and the surrounding capillaries plasma Reabsorption in the proximal tubule •because all plasma soolutes besides proteins are able to enter the glomerular ultrafiltrate freely the total solute concentration (Osm) of the filtrate is ~ to plasma (300 mOsm) or "isosmotic" with plasma •reabsorption cannot occur unless the solute concentrations of the plasma in the peritubular capillaries and the filtrate are altered by active transport processes -> achieved by active transport of Na+ from the filtrate to the peritubular blood along with Cl, K, H, NH4, HCO3, water, glucose Active and passive transport •epithelial cells that compose the wall of the proximal tubules are joined by tight junctions only toward their apical sides (closest to lumen) -> each cell has four exposed surfaces, the apical facing the lumen which contains microvilli, the basal side facing the peritubular capillaries, and the lateral sides facing the narrow clefts between adjacent epithelial cells •concentration of Na+ in filtrate ~ plasma -> however, the cytoplasm in epithelial cells are lower caused by Na+/K+ pumps on the basal and later sides but not in the apical membrane -> creates a gradient that favors the diffusion of Na+ from the tubular fluid across the apical plasma membranes and into the epithelial cells of the proximal tubules -> Na+ is then extruded into the surrounding interstitial (tissue) fluid by the Na+/K+ pumps transport of Na+ from the tubular fluid to the interstitial fluid creates a potential difference with the lumen as a negative pole -> favors passive transport of Cl- toward the higher Na+ concentration in interstitial fluid •in the early proximal tubule the reabsorption of Cl- occurs by transcellular transport through epithelial cells due to insufficient Na+ reabsorption •as a result Cl- can be passively reabsorbed by paracellular transport -> the tight junctions between the epithelial cells of the nephron are the leakiest in the proximal tubule, making it an ideal spot for paracellular transport for passive reabsorption of salt and water -> results in an accumulation of NaCl in interstitial fluid surrounding the proximal tubule -> raisin osmolality -> creates an osmotic gradient that drives the reabsorption of water through aquaporin channels in the plasma membrane of the epithelial cells -> NaCl and water that was reabsorbed can then move passively into the surrounding peritubular capillaries and returned to the blood Significance of proximal tubule reabsorption •65% of salt and water in the original filtrate is reabsorbed and returned to the vascular system -> volume of tubular fluid remaining is also reduced but still has a 300 mOsm •an additional small amount of salt and water (about 20%) is returned to the vascular system by reabsorption through the descending limbs of the nephron loop -> occurs constantly regardless of hydration state and is not subject to hormonal regulation compared to the distal and collecting ducts -> therefore 85% of filtered salt and water is reabsorbed in a constant fashion and is very costly (ATP) accounting in 6% of calories burned at rest only 15% of the original filtrate makes it the distal convoluted tubule and collecting duct -> 27 L a day (15% of 180 L) -> fine-tuning at this stage occurs by the action of hormones on later regions of the nephron

Renal acid-base regulation

kidneys regulate blood pH by excreting H+ into the urin and by reabsorbing bicarbonate -> normal urine contains little bicarbonate and is slightly acidic (5-7 pH) due to reabsorption ability reabsorption of bicarbonate and secretion of H+ •cell of the proximal tubule use Na+/H+ carriers to transport H+ into the filtrate in exchagne for Na+ from the filtrate -> antiport as Na+ and H+ move in opposite directions •antiport cotransport is a form of secondary active transport -> as Na+ diffuses down conctration gradient formed by Na+/K+ pumps in the basolateral portion -> most of H+ is secreted into the filtrate from the proximal tubule is used for reabsorption of bicarbonate the apical membrane of the tubule cells (facing the lumen) are impermeable to bicarbonate -> reabsorption of bicarbonate occurs indirectly •when urine is acidic bicarbonate combines with H+ to form carbonic acid -> carbonic acid in filtrate is converted to CO2 and H2O by carbonic anhydrase -> enzyme is located in apical plasma membrane of the proximal tubule in contact with fitrate tubule cell cytoplasm also contains carbonic anhydrase -> as CO2 concentrations increase in filtrate, the CO2 diffuses into tubule cells -> through enzyme it is converted to carbonic acid -> dissociates to bicarbonate and H+ within tubule cells -> bicarbonate then diffuses through the basolateral membrane and into blood •the proximal tube reabsorbs 80-90% of filtered bicarbonate -> process leaves very little H+ in filtrate, however urine is still more acidic than plasma -> caused by distal tubule that secretes H+ into filtrate using primary active transport H+ ATPase pumps (primary activity resonsible for acidification of urine) -> H+ in the urine is buffered by ammonium and phosphate buffers if a person has alkalosis, less H+ is present in filtrate -> less bicarbonate is reabsorbed -> resulting excretion of bicarbonate helps to compensate for alkalosis •if a person has acidosis the proximal tubule cells can make extra bicarbonate -> formed by metabolism of AA glutamine, from glutamic acid -> results in two bicarbonate ions and two molecules of ammonia (NH3) and is converted into ammonium ion (NH4+) -> extra bicarbonate helps to compensate for acidosis serving as a urinary buffer disturbances in acid-base balance caused by respiratory problems can be partially compensated for by changes in plasma bicarbonate concentration •primary metabolic acidosis -> overproduction of ketone bodies or lactic acid -> decreases plasma bicarbonate concentration •primary metabolic alkalosis -> increased plasma bicarbonate levels by loss of acidic gastric juice (ex. vomiting) or impaired ability of kidneys to excrete bicarbonate •these primary disturbances in metabolic component are compensated for by secondary changes in the respiratory component

Clinical application: nephrolithiasis "kidney stones"

kidneys stones are hard objects formed in the kidneys as a result of crystallized minerals or waste production, about 80% are calcium stones composed of calcium phosphate or calcium oxalet struvite stones are are crystals of magnesium ammonium phosphate that may result from UIs if a person has oto much uric acid due to a genetic defect uric acid can precipitate in the joints to cause gout and can precipitate to the renal tubules to produce uric acid stones because stones form when their components concentrations exceed their solubility the tendency to form stone is increased if the person is dehydrates large stoens in the calcyces or pelvis may obsruct urine flow and while smaller stones less than 5 mm that pass through the ureter can produce immense pain -> medications may help to pass the stone but if the stones don't pass the person may need lithotripsy where energy generated by a lithtripter device produces shock waves to travel through tissues and shatter stones -> if this doesn't work surgery may be needed

Clinical investigation: Lauren

lauren appeared to develop a nephrogenic diabete insipidus -> result of lithium she took for bipolar disorder -> diabetes led to increaesed excretion of dilute urine -> need to constantly drink water probenecid inhibits the reabsorption of uric acid -> kidneys can clear uric acid form her blood more quickly as a tretment for her gout -> probenecid also inhibits OATs slowing the secretion of antibiotics -> increasing effectiveness plasma creatinine measurement and her age, sex, and weight gave a normal estimated GFR -> healthy kidneys developed hypokalemia as a result of taking hydrochlorothiazide -> promotes K+ secretion into nephron tubules used a diuretic to treat her hypertension -> prescribed a potssium-sparing diuretic -> blocks K+ secretion or aldosterone action possibly in combo with hydrochlorothiazide

Blood Gas measurements

measurement of O2 content in blood (O2 mL/100mL) •use of an oxygen electrode -> produces a current in proportion to the concentrated dissolved oxygen •the max is attained when the fluid is saturated with O2 -> depends on solubility constant, temp, and Po2 -> if temperature is held constant than it all depends on Po2, allowing you to measure it assuming that fluid has the same Po2 as the gas •po2 of gas is 152 mmHg -> calibrate oxygen electrode to this point -> a lower Po2 measured indicates less oxygen is dissolved, while a higher indicates the reverse •ex. you measure a blood sample to have 100mmHg, and an alveolar air to have 105 mmHg -> can state that blood and air is almost in complete equilibrium the oxygen electrode responds only to oxygen dissolved in water or plasma; it cannot respond to oxygen that is bound to hemoglobin in red blood cells -> most O2 is located in RBCs attached to hemoglobin -> oxygen content of whol blood depends on both its Po2 and RBC/hemoglobin content •ex. Po2 of 100 mmHg, only .3 mL of O2 is dissolved in the plasma and 19.7 mL of O2 is found within RBCs -> the .3 mL is affected by Po2 and thus would be unchanged if RBCs were removed

Physical aspects of ventilation

movement of air from higher to lower pressure between the conducting zone and the terminal bronchioles occurs as a result of pressure difference between the two ends of the airways •air flow through bronchioles like blood flow through blood vessels is directly proportional to the pressure difference and inversely proportional to the frictional resistance to flow •pressure differences in the pulmonary system are induced by changes in the lung volumes •the compliance, elasticity, and surface tension of the lungs are phsycial properties that affect their functioning

Muscle Myolobin

myoglobin is a red pigment found in striated muscle cells -> in particular slow-twitch aerobically respiring skeletal fibes and cardiac muscle -> aerobic exercise training increases skeletal muscle myoglobin myoglobin is similar to hemoglobin but has one heme compared to four -> only binds to one molecule of O2 myoglobin has a higher affinity for oxygen than does hemoglobin and its dissociation curve is to the left of the oxyhemoglobin dissociation curve -> myoglobin curve is rectangular indicating oxygen will be released only when Po2 is very low because the Po2 in the mitochondria is very low (O2 -> H2O) myoglobin may act as a "go-between" in this transfer •may also have an oxygen-storage function important in the heart -> during diastole the coronary blood flow is greatest, myoglobin can load up with oxygen -> released during systole as coronary arteries are squeezed close CO binding for myoglobin is even greater than in hemoglobin -> binding to cardiac myoglobin leads to myocardial depression, hypotension, and arrhythmias -> cardiac decompensation results in further tissue hypoxia and death

Affinity of hemoglobin for oxygen

normal arterial blood at sea level unloads 22% of its oxygen to tissues at rest -> saturation goes from 97% to 75% in venous blood • at high altitudes the affinity of hemoglobin for oxygen is reduced so that a higher proportion of oxygen is unloaded

Clinical application: obstructive sleep apnea

obstructive sleep apnea is a condition in which there are 15 or more period of apnea during sleep caused by temporary blockage of the upper airway •more common in men than women, and obesity is a risk factor the upper airway of the oropharynx is normally kept open by contractions of over 20 diff. skeletal muscle where the pharyngeal air passages narrow during sleep to cause apnea arterial Po2 and oxyhemoglobin saturation fall and the arterial Pco2 rises to stimulate chemoreceptor reflexes which can cause apnea to end with a gasp and jerk snoring, sleepiness/fatigue during the day, morning headache caused by vasodilation are other symptoms, with dangers including pulmonary hypertension that canlead to ventricle hypertrophy those affected must wear a CPAP (continuous positive airway pressure) when they sleep to keep their oropharynx air passage open

Clinical application: acute mountain sickness (AMS)

occurs in high elevations when acclimatization is not reached kidneys have a diuretic response to high altitude -> diuresis produces hypovolemia (decreased blood volume) helping to mitigate AMS -> response can be aided by acetazolamide -> inhibits carbonic anhydrase -> decreases renal reabsorption of bicarbonate and water -> mild diuretic effect and metabolic acidosis -> metabolic acidosis produced by renal excretion of bicarbonate helps to counter respiratory alkalosis caused by hyperventilation at high altitude metabolic acidosis works together with th ehypoxic ventilatory response of the carotid bodies to produce a higher total minute volume than at sea level aiding acclimizatization

passive immunity

passive immunity refers to immune protection produced by the transfer of antibodies from a human or animal donor (ex. Rhogan, anti-D antibodies) •a person has been actively immunized and produces anitbodies, these antibodies are then transfered to others -> occurs naturally in transfer from mother to fetus during pregnancy and nursing -> ability to mount a specific immune response, called immunological competence does not develop for a month or so after birth •why the fetus cannot immunologically reject its mother -> some IgG antibodies enter fetal circulation and serve to confer passive immunity to the fetus •due to the baby not producing its own lymphocyte clones needed to form these antibodies, passive immunity gradually disappears -> need for breast feeding at least 6 months so the baby can receive additional antibodies of primarily IgA and some IgG, especially colostrum a pre milk secretion rich in antibodies another example of passive immunity are people who have been exposed to extremely virulent infection or toxins such as tetanis, hepatitis, rabies, and snake venom •the affected is injected with an antiserum (ex. antivenom, or Rhogam), also called antitoxin from an individual/animal previously exposed -> donor develops lymphocyte clones and active immunity, and thus has a high concentration of antibodies -> if patient is affected again they will once again need the antiserum do to not producing any of their own antibodies intravenous immunoglobulin (IV injection of gamma globulin) are pooled plasma samples from countless people with a diversity of IgG originally used in individuals with primary immunodeficiency disease •now used mostly to treat patients with autoimmune conditions and cancer patients with compromised immune systems •get a bell curve of results if a antigen is present depending on how accurate an antibody is to an antigen monoclonal antibodies specific for a particular antigen can be collected from animals and result in a pure clonal cell -> this B lymphocyte is then fused in vitro with a cancerous myeloma cell to form an immortal hybrid cells that divides indefinitely called a hybridoma -> secretes antibodies-specific for a single antigenic-determinant site -> has allowed for monoclonal antibody medications (-mab medications) -> these have been approved to target cytokines (tumor necrosis factor), IgE, and other regulatory molecules in autoimmune disease •ex. trastuzumab "herceptin" -> targets HER2 receptor produced by 30% of invasive breast cancers •ex. bevacizumab "Avastin" -> blocks the binding of vascular endothelial growth factor (VEGF) to its receptors for treatment of types of colorectal, lung, kidney, and brain cancers

Clinical Application: hyperbaric oxygen therapy (HBOT)

patient breath 100% oxygen at 2-3 atm pressure -> does not increase oxygen hemoglobin saturation, bur rather increases the oxygen carried by the plasma from .3 mL/100mL of blood at sea level up to 6mL/100mL for 100% oxygen at 3 atm •used as treatment for decompression sickness from scuba diving -> due to Boyle's law when raising pressure decreases the size of bubbles HBOT can also kill anaerobic bacteria and is used to treat gas gangrene caused by bacteria that produce gas and tissue necrosis can also be used to treat CO poisoning, severe traumatic injuries, certain inflammations, diabetic sores, and other conditions

Labor and parturition

powerful contractions of uterus are needed for labor -> done so by two agents •oxytocin -> polypeptide hormone made in hypothalamus and released by posterior pituitary (also made in uterus) •porstaglandins -> class of cyclic FA with paracrine functions produced in uterus -> particulary PGF2å and PGE2 •labor can be induced using these parturition in animals such as pigs, rats, is aided by a hormone called relaxin -> softening of pubic symphysis and relaxation of the cervix -> may help in relaxation of pelvic girdle in humans acting on tendons and ligaments •relaxin secreted by the human ovary with progesteron are required during the first trimester for the decidual reaction (formation of decidual basalis in the endometrium) -> relaxin promotes the growth of blood vessels into teh edecidua basalis helping to nourish the growing embryo following delivery of the baby, oxytocin i sneeded to maintain the muscle tone of the myometrium and to reduce hemorrhaging from uterin arteries -> oxytocin may also play a role in promoting the involution (reduction in size) of the uterus following delivery

Clinical application: probenecid

probenecid is a drug used to treat gout by improving the ability of the kidneys to eliminate uric acid from the blood -> inhibits the uric acid transporters in the cells of the proximal tubule reducing the renal reabsorption of uric acid and promoting excretion during WWII penicillin was in short supply, probenecid was used to inhibit the organic anion transporters (OATs) in the proximal tubule -> reducing the renal secretion of penicillin -> increased effectiveness and decreasing its nephrotoxicity probenecid may still be used in severe infections to increase effectiveness of penicillin and other antibiotics including ampicillin and cephalosporin that are secreted into the nephron by OATs

vital signs: dying to deliver

problem was an eveted uterus -> uterus is delivered with the baby there are three stages to delivery process; 1. labor -> contraction pull the cervix open to allow delivery 2. delivery -> expels babye 3. placenta passes -> can take an half hour or more after delivery in this case a tired intern had attempted to pul out the placent leading to the everted uterus -> bleading through arteries in uterus -> had tried to massage the uterus back into place but a flaccid uterus has no way to stop blood from flowing through the torn channels during a delivery blood flow through the uterus can be almost a quart a minute her hemoglobin was crashing -> wouldn't accept any blood hemorrhage is one of the few remaining cuases of maternal death but can usually be stoped with surgery they had to remove the uterus or she would die " hysterectomy" -> was a success and within days she was up and walking

Clinical application: Creatinine

produced by muscles form creatine and released in plasma -> concentration can be used to assess kidney function creatinine is filtered in the kidneys and not reabsorbed, but is slightly secreted by tubules giving it a renal plasma clearance a little greater than inulin (slightly greater than true GFR) however using a person's age, sex, weight it can be used to make a estimated GFR (eGFR) also the ratio of the plasma concentrations of urea (called BUN - blood urea nitrogen - test) to creatinine provides additional information about kidney health

Immunological tolerance

production of antibodies against non-self (foreign) antigens while tolerating self-antigens occurs during the first month or so of postnatal life •the ability of an individual's immune system to recognize and tolerate self-antigens requires continuous exposure -> if this occurs well the immune system is weak such as in new borns the tolerance is more complete and long lasting (some antigens are hidden "immunological protected zones") •antibodies made against self-antigens are called autoantibodies •killer T cells that attack self-antigens are called autoreactive T cells mechanisms of immunological tolerance include •clonal deletion -> lymphocytes that recognize self-antigens are destroyed •clonal anergy (means "without working") -> lymphocyte that recognize self-antigens are prevented from becoming activated •central tolerance -> mechanisms for T and B cells -> central tolerance in the thymus is achieved by apoptosis and removal of autoreactive T cells, while B cells in bone marrow may involve both clonal deletion and anergy •peripheral tolerance -> lymphocytes outside of the thymus and bone marrow is due to complex mechanisms resulting in anergy -> peripheral tolerance mechanism are needed due to randomly generated antigen receptors in lymphocyte progeny -> while beneficial for diseases, this receptors for self-antigens would result in autoimmune diseases otherwise -> suppression is achieved by regulatory T cells

Clinical Application: Respiratory distress syndrome (RDS)

respiratory distress syndrome (RDS) is caused by alveoli collapsing in a neonate due to lack of surfactant -> occurs in 60% of babies born less than 28 weeks of gestation (normally pregnancy is 37-42 weeks), 30% of babies born at 28-34 weeks, and less than 5% of babies born after 34 weeks most babies can be saved by the use of mechanical ventilators and by exogenous surfactant delivered into the baby's lungs by an endotracheal tube until the baby can produce its own people with lung injury caused by septic shock may develop acute respiratory distres syndrom (ARDS) inflammation caused by increased capillary and alveolar permeability -> production of protein rich fluid in lungs -> reduction of compliance and surfactant production -> leads to hypoxemia (low blood oxygen) of the blood leaving the lungs severe hypoxemia can be fatal, but survival has improved in recent years with intervention

Disease caused by the immune system

the ability of the normal immune system to tolerate self-antigens while it identifies and attacks foreign antigens provides a specific defense against invading pathogens •when this system attacks itself it can result in severity from sniffles to sudden death diseases caused by the immune system can be grouped into three interrelated categories 1. autoimmune diseases 2. immune complex diseases 3. allergy "hypersensitivity" these diseases are not caused by foreign particles, but by an abnormal response of the immune system

Inspiration and expiration

the diaphragm innervated by two phrenic nerves composed of axons originating in C3 through C5 of the spinal cord separates the thoracic and abdominal cavities and is the primary muscle of ventilation •aided by muscles that insert on the ribs between the bony portions of the rib cage ar etwo layers of intercostal muscles the external intercostal muscles and the internal intercostal muscles between the costal carilages, there is only one muscle layer, and its fivers are oriented similar to those of the internal intercostals -> muscle is known as the interchondral part of the internal intercostals also called parasternal intercostals an unforced, quiet, inspiration results primarily from contraction of the dome-shaped diaphragm, which lowers and flattens when it contracts -> increases thoracic volume in the verticle direction •inspiration is aided by contraction of the parasternal and external intercostals, which raise the ribs when they contract and increase the thoracic volume laterally other thoracic muscles become involved in deep inspiration •most important is the scalenes, followed by the pectoralis minor, and in very labored breathing the sternocleidomastoid muscles -> contraction of these mscles elevates the ribs in an anteroposterior direction and stabilize the rib cage so that the intercostals can be more effective •the increase in thoracic volume produced by these muscle contractions decreases intrapulmonary (intra-alveolar) pressure -> cuasing air to flow to the lungs Quiet expiration is a passive process •after becomeing stretched by contractions the thorax and lungs recoil as a result of their elastic tension when the respiratory muscles relax •decrease in lung volume -> raise pressure within the alveoli above atmospheric pressure -> air is pushed out during forced expiration the internal intercostal muscles (excluding the interchondral part) contract and depress the rib cage -> aided by abdominal muscles -> contraction pushes organs up against the diaphram further decreasing the volume of the thorax -> greatly increases intrapulmonary pressure to produce a more forceful expiration pulmonary function may be assessed clinically by means of a technique known as a spirometry •subject breaths into a close system in which air is trapped within a light plastic bell floating in water -> bell goes up when subject exhales and down upon inhalation -> movements correspond with a pen which traces a record known as a spirogram •can be used to measure vital capacity which is the maximum amount of air that can be forcefully exhaled after maximum inhalation

Collecting duct: effect of antidiuretic hormone (ADH)

the fluid that passes into the collecting ducts in the cortex is hypotonic (50-100 mOsm) -> the collecting duct is impermeable to the high salt concentration of the interstitial fluid -> it is permeable to water -> drawn out water does not dilute the salt due to being transported by capillaries to the general circulation -> returns to vascular system -> driving of water reabsorption is caused by the osmotic gradient •rate of osmosis across the walls of collecting ducts can be modified in permeability to water by regulating the number of aquaporins this is cone by arginine vasopressin (ADH) which responds to as little as a 1% increase in plasma mOsm -> stimulates an increase in water permeability of the collecting duct allowing for osmosis • at high enough concentrations this hormone can lead to reabsorption of NaCl from thick portion of the ascending loop and stimulation of urea transporters in the inner medullary duct-> contributes to water reabsorption by promoting entry of urea into the interstitial fluid •main purpose is regulation through aquaporins in collecting duct when ADH binds to cells in collecting duct -> cAMP production -> exocytosis like release of aquaporins in collecting duct cells -> when ADH is longer available these channels are removed by endocytosis •if ADH was absent urince concentration would be mOsm and 18 L of urine would be removed daily ADH is produced by neurons in the hypothalamus and is released by the posterior pituitary -> stimulated by osmoreceptors in hypothalamus and respond to increased mOsm (~280-295mOsm) •hypothalamus serves the thirst center -> water loss will lead to thirst •at max ADH response only 400 mL is excreted (99.8% of glomerular filtrate is reabsorbed) a person in a state of normal hydration excretes about 1.5 L of urine per day (99.2% reabsorption) even without ADH present some water is still absorbed through the collecting ducts Effects of drinking seawater -> the high salt concentration in seawater is more than the body needs and must be excreted -> causes more water to remain inside the kidneys and be urinated out along with other salt of water (osmotic diuresis) -> more water is urinated out than taken in

Diuretics and Renal function tests

the importance of renal function in maintaining homeostasis makes the clinical study of renal function and urine composition particularly useful people who need to lower their blood volume because of hypertension, congestive heart failure, or edema take diuretics that increase urine excreted -> directly lower blood volume and pressure by increasing the proportion of the glomerular filtrate that is excreted as urine, they can also decrease interstitial fluid volume (ex. edema) by a more indirect route •lowering plasma volume -> increase oncotic pressure -> osmosis of intersititial fluid into capillary blood -> reduce edema various diuretic drugs act on the renal nephron in different ways -> they are based on chemical structure, or aspects of their actions (ex. loop diuretics, thiazides, carbonic anhydrse inhibitors, osmotic diuretics, and postassium-sparing diuretics loop diuretics -> furosemide "lasix" -> most powerful diuretics (25% reduction) -> inhibit Na+ - K+ - 2Cl- cotransporters in thick segments of the ascending loop thiazide diuretics -> hydrochlorothiazide -> inhibit salt and water reabsorption (8%) through inhibition of salt transport by first segment of the distal convoluted tubule by the Na+- Cl- cotransporters carbonic anhydrase inhibitors -> acetazolamidea "diamox" -> weaker diuretics -> act on proximal tubule to prevent water reabsorption that occurs when bicarbonate is reabsorbed -> promotes urinary excretion of bicarbonate -> used to treat mountain sickeness osmotic diuretics -> extra solutes in filtrate increase osmotic presure of filtrate and decrease reabsorption of water -> mannitol •similar effect in diabetes with glucose in filtrate all listed diuretics -> result in increased delivery of Na+ to cortical collecting ducts which directly and in indirectly stimulate increased K+ secretion -> excessive elimination of K+ into urine -> can cause hypokalemia -> produce neuromuscular disorders and ECG abnormalities -> need to supplement food with KCl potassium-sparing diuretics -> spironolactones "aldactone" -> aldosterone antagonists -> block aldosterone stimulation of Na+ reabsorption and K+ secretion •Triamterene "dyrenium" -> acts on tubule more direclty to block Na+ reabsorption and K+ secretion combinations of spironolactone or triamterene together with hydrochlorothiazide are sometimes prescribed for hypertension

Juxtaglomeruar apparatus

the juxtaglomerular apparatus is the region in each nephron where afferent arteriole comes into contact with the last portion of the thick ascending limb of the loop •granular cells within the afferent arteriole secrete the enzyme renin into the blood •also contains macula densa renin catalyzes the conversion of angiotensinogen -> angiotensin I -> angiotensin II by angiotensin converting enzyme (ACE) as blood passes through capillaries in the lungs -> secretion of renin into the plasma by granular cells of the juxtaglomerular apparatus results in increased production of angiotensin II -> stimulates adrenal cortex to secrete aldosterone •secretion of renin from granular cells therefore initiates the renin-angiotensin-aldosterone system •conditions that lead to increased renin secretion -> increased aldosterone secretion -> promote reabsorption of Na+ from cortical collecting ducts into the blood angiotensin II in blood has been known to raise systemic blood pressure as a result of vasconstriction and to stimulate aldosterone secretion •angiotensin II produced within the kidneys stimulates Na+ reabsorption by promoting activity of Na transporters in renal tubules -> stimulates vasconstriction of afferent and efferent arterioles -> decrease in GFR and Na excretion -> rise in blood volume and pressure Regulation of Renin Secretion •inadequate dietary intake of salt is accompanied by a fall in blood volume -> decreased plasma concentration inhibits ADH secretion -> less ADH lead to less water reabsorbed and more excretion -> fall in blood volume and renal blood flow results in renin secretion -> increased renin secretion is amplified by direct effect of blood pressure on granular cells which function as baroreceptors in the afferent arterioles, renin secretion is also stimulated by sympathetic nerve activation of ß1-adrenergic receptors in the granular cells of the juxtaglomerular apparatus (seen in baroreceptor reflex which increases sympathetic activity in response to fall in blood volume) •increased secretion of renin -> increased aldosterone secretion -> less Na+ is excreted and more is retained

Partial pressure of gases in blood

the large SA of alveoli and the diffusion distance bring oxygen and carbon dioxide in the blood and air into equilibrium -> aided by sheet like capillaries surrounding the alveoli when liquid and gas, such as blood and alveolar air are in equilibrium mas value of gas exchange occurs, according to henry's law -> depends solubility of gas in fluid (physical costant), temperature of fluid, and partial pressure of the gas) •because solubility is a constant, and the temp. is fairly constant, the concentration of gas dissolved in a fluid (such as plasma) is directly dependent on partial pressure when water or plasma is brought into equilibrium with air at Po2 of 100 mmHg, the fluid will contain .3 mL of O2 per 100 mL fluid at 37˚C •if the Po2 of the gas is reduced by half the amount of dissolved would also be reduced by half

Compliance

the lungs are very distensible (stretchable) structures -> this ability is termed compliance •lung compliance can be defined as the change in lung volume per chane in transpulmonary pressure (∆V/∆P) -> at a given transpulmonary pressure will cause greater or lesser expansion depending on lung compliance -> this ability may be caused by the alveolar ducts and sacs rather than indvidual alveoli due to these being the major strcutures that expand during inspiration while alveoli inflation is primarily to secondary alveolar recruitment •if the lungs were filled with concrete a given transpulmonary pressure would produce no increase in lung volume and no air would enter -> compliance = 0 •infiltration of lung tissue with connective tissue proteins "pulmonary fibrosis" can similarly decrease compliance by giving the lungs a leathery like appearance

endocrine functions of the placenta

the placenta secretes both steroid homrones and protein hrmones -> chorionic gonadotropin (hCG), growth hormone-variant (hGH-V) "placental growth horomone (PGH), chorionic somatomammotropin (hCS) "placental lactogen (hPL)" these have similar action to counterparts in anteiror pituitary hormones -> hCG has LH like effects, hGH-V works like a growth hormone and supplants maternal GH, which stops being secreted around week 21-25 •hCS supplement these actions -> similar to prolactin although no evidance thus far pituitary-like hormones of placenta •hCS acts together with growth hormone from the mother's pituitary to produce a diabetic-like effect in pregnant women -> promote lipolysis and increased plasma FA concentration, glucose sparing by maternal tissues -> increased blood glucose, and polyuria producing dehydration and thrist •this diabetic effects helps to ensure a sufficient supply of glucose for the placenta and fetus •beta cells in the motehr's pancreatic islets proliferate during pregnancy to supply insulin so that the development of gestational diabetes is prevetned steroid hormones form the placenta •after 5.5 weeks and the corpus luteum regresses the placenta becomes the major sex-steroid producing gland -> 100 x estrogen level than at beginning of pregnancy as well as progesterone changing the estrogen/progesterone ratio in blood from 100:1 at the beginning of pregnancy to close 1:1 toward full-term -> progesterone relaxes the smooth muscle of the myometrium reducing myometrial contractility during preganancy the placenta however is an "incomplete endocrine gland" because it cannot produce estrogen and progesterone w/o precursors supplied by the mother and fetus -> need of cholesterol from the mother rather than conversion from acetate -> cholesterol can be converted into progesterone -> placenta lacks hormones to convert progesterone to androgens -> androgens are thus made by the fetus •fetus and placenta function together in production of steroid hormones an association termed as the fetal-placental unit -> ex. fetal adrenal cortex secretes androstenedione -> placenta converts to estriol -> makes up 90% of estrogens excreted in mother's urine in third trimester -> this hormone can be used to measure placenta health

Structure and function of the kidneys

the primary function of the kidneys is regulation of the extracellular fluid (plasma and interstitial fluid) environment of the body -> formation of urine -> modified filtrate of the plasma -> during formation kidneys regulate; •volume of blood plasma -> significant regulation to blood pressure •concentration of waste products •concentration of electrolytes (Na+, K+, carbonate, other ions) in plasma •pH of plasma kidneys also secrete erythropoietin -> stimulates RBC function kidneys lie on either side of the vertrebral column below the diaphragm and liver and weigh about 160 g and about the size of a fist •urine produced is drained into hollow cavities known as renal pelvis "basin" and channeled form the kidney via long ducts known as ureters to the urinary bladder •the outer cortex is reddish brown and granular in appearance because of its many capillaries •the deeper region, or medulla is striped in appearance due to the presence of microscopic tubules and blood vessels -> composed of 8-15 renal pyramids separated by renal columns cavity of kidney is divided into several sections •each pyramid projects into a small depression called a minor calyx "bud or husk" -> several minor calyces unite to form a major calyx -> join to form a funnel-shaped renal pelvis -> renal pelvis collects urin from the calyces and transports it to the ureters and urinary bladder •ureter undergoes peristalsis (why there is immense pain with kidney stones) -> pacemaker of these waves is locatd in the renal calyces and pelvis which contain smooth muscle -> thee peristaltic contractions affect transport properties of the renal tubules and influence the concentration of urine The urinary bladder is a storage sac for urine -> shape determined by amount of urine -> drains into the urethra •in females the urethra is 4 cm long and opens into space between the labia minora above the vaginal opening -> makes vaginal infection easier -> why female are prone to UIs • in males the urethra is 20 cm long and opens at tip of penis form which it can discharge semen or urine -> as urethra leaves the bladder it is encircled by the prostate gland which can become enlarged impeding urination in elderly men

Respiratory System

the term respiration includes three separate but related functions; 1. ventilation -> breathing 2. gas exchange -> occurs between the air and blood in the lungs and between blood and other tissues of the body 3. oxygen utilization -> internal regulation by tissues in energy liberating reaction of cell respiration •ventilation and exchange of gases (O2 and CO2) between the air and blood is termed external respiration •gas exchange between the blood and other tissues and oxygen utiliztaion by tissues is termed internal respiration ventilation is a mechanical that moves air into and out of the lungs •because O2 concentration is hgiher in air than lungs diffusion favors diffusion from air to blood -> CO2 moves from blood to air by also diffusion down concentration gradient (reverse of O2) -> as a result of the two inspired air contains more O2 and less Co2 than expired air •blood leaving the lungs (in pulmonary veins) has a higher O2 and lower CO2 concentration than blood delivered to the lungs in the pulmonary arteries -> caused by luns funtion to bring blood into gaseous equilibrium with the air gas exchange between air and blood occurs entirely by diffusion through lung tissue •diffusion is rapid due to the large SA of the lungs and very small diffusion distance between air and blood •air at sea level consists of 78% N2, 21% O2, .04%CO2, and a small amount of other gases -> we exhale 16% O2, and 3-5% CO2 with the rest being mostly N2

mechanics of breathing

the thorax must be sufficiently rigid to protect vital organs and provide attachments for a number of short, powerful muscles •breathing "pulmonary ventilation" requires a flexible hotrax that can function as a bellows during the ventilation cycle •the structure of the rib cage and associated cartilages provides continuous elastic tension -> when stretched by muscle contraction during inspiration the rib cage can passively return to its resting dimensions when the muscle relax -> elastic recoil is greatly aided by the elasticity of the lungs pulmonary ventilation consists of two phases; inspiration and expiration •accomplished by alternately increasing and decreasing the volume of the thorax and lungs

Control of micturition

the urinary bladder has a muscular wall known as a detrusor muscle -> numerous gap junction interconnect its smooth muscle cells allowing action potentials to spread -> although action potentials can be automatically generated by stretching the detrusor muscle is innervated by parasympathetic neurons and neural stimulation is required for the bladder to empty -> major stimulus for bladder emptying is ACh released by parasympathetic axons which stimulate muscarinic ACh receptors in the detrusor muscle -> drugs that block specific muscarinic ACh receptors in the bladder are now available to treat overactive bladder (detrusor muscle) two muscular spintors surround the urethra •upper sphincter -> composed of smoth muscle "internal urethral sphincter" -> no voluntary control •lower sphincter -> composed of voluntary skeletal muscle "external urethral sphincter --kegel exercises can strengthen muscles of the pelvic floor and the external sphincter -> weakness in these pelvic floor muscles can lead to incontinence -> regulation of these sphincters are regulated in the process or urination "micturition" when the bladder is filling sensory neurons in the bladder are activated by stretch stimulated interneurons located in the S2-S4 segments of the spinal cord -> spinal cord controls the guarding reflex -> parasympathetic nerves to detrusor muscle are inhibited while the striated muscle of the external urethral sphincter is stimulated by somatic motor neurons -> prevents involuntary emptying of bladder When the bladder is sufficiently stretched sensory neuron stimulation can evoke a voiding reflex -> sensory info passes up spinal cord to a group of neurons forming a micturition center -> activates parasympathetic nerve to detrusor muscle causing rhythmic contractions and relaxation of internal urethral sphincter -> leads to sense of urgency -> still have control of voluntary control innervated by somatic neurons of the pudendal nerve the guarding reflex permits bladder filling because highe rbrain regions inhibit the micturition center in the pons -> higher regions include prefrontal cortex, & insula which switch from guarding to voiding reflex -> allows for voluntary control of micturition -> once decision is made the micturition center in the pons becomes activated by sensory information monitoring bladder stretch -> pudendal nerve activity is inhibited so external sphincter can relax -> parasympathetic nerve to detrusor is activated causing contraction of the bladder and voiding of urine -> this ability to inhibit micturition develops around 2-3 yrs old adults who have damaged spinal chord disrupting the signals of the pelvic muscles and external urethral sphincter rever to the spinal reflex of infancy and become incontinent -> need a urinary (Foley) catheter inserted so urine collects in a plastic bag

Birth process

the uterus has contractions throughout pregnancy -> light at first lasting 20-30 seconds every 15 minutes -> near end of pregnancy they become stronger and can create "false-labor" feelings known as braxton hicks contractions -> true labor is marked by contractions that last for 40 seconds or longer every 15-20 minutes •caused by positive feedback mechanism -> Uterine contractions induce stretching of cervix -> release of oxytocin from posterior pituitary gland -> sitmulates uterni muscles both direclty and through prostaglandins -> contractions push fetus downward -> cycle repeats until baby is pushed out •prior to first stage of parturition there can be a "blood show" cuased by the expulsion of mucous plug form the cervical canal -> plug prevents bacteria and sperm from entering Stage 1 •no movement down vaginal canal -> uterin contracts of labor occur so that cervical canal slowly disappears as lower part of uterus is pulled upward toward the fetus' head -> processed called effacement "taking up cervix" -> head acts as a wedge to assist cervical dilation -> amniotic sac is likely to break releasing amniotic fluid which leaks out of vagina "water breaks" (if born in sace birth is known as en-caul birth) -> first stage ends once cervix id dilated completely (10 cm) stage 2 •uterin conctractions occur ever 1-2 minutes and last about 1 minute as fetus begins its movement through the cervix and down the vaginal canal -> accompanied with desire to push or bear down "valsalva's maneuver" -> fetus head gradually descends into vagina -> increased desire to push -> women often squats using abdominal muscles to push and reduce tearing of perineum •when baby's head reaches the exterior it turns so that the back of the head is uppermost (looking at doctor) to enlarge the vaginal orfice an "episiotomy" is often performed -> sewn up later once baby is breathing normally the umbilical cord is clamped and cut severing the child from the placenta -> stump of cord shrivels to become the "navel" (umbilical) Stage 3 •the placenta "afterbirth" is delivered during the third stage of parturition -> about 15-30 minutes after delivery of baby -> uterine muscular contractions shrink uterus and dislodge the placenta -> once expelled stage 3 is complete if fetus does not turn a "breech birth" is likely -> cervix cannot expand enough and asphyxiation of baby will likely occur -> need of C-section (otherwise 30% of births are by C-section far more than should) newborn characteristics •skin may be covered in white, greasy, cheese-like substance called vernix caseosa which protects skin •intestines are filled with a green-past-like material called meconium -> eliminated with time •maternal hormones may cause the breasts in both male and female newborns to swell and secrete milk •maternal hormones which are decreased following birth can cause newborn girls to have a period (menses)

Gas exchange in the lungs

through the use of a glass U-tube filled with fluid we can measure the pressure the atmosphere and gases exert •water at sea level will be pushed up to a height of 33.9 (11,332 mm), whereas mercury (Hg), which is more dense, will be raised to a height of 760 mm -> why in barometers we use Hg and 1 atm is = 760mmHg "760 torr" (after Evangelista Torricelli, who invented the tool in 1643) according to dalton's law, the total pressure of a gas mixture is equal to the sum of pressure that each gas in the mixture exerts independently -> the pressure of an individual gas in the mixture is known as partial pressure equal to the product of the total pressure and the fraction of that gas in mixture dalton's law can be restated as follows; •total pressure of gas mixture is equal to the sum of the partial gases of the constituent gases •because O2 makes up 21% of the atmosphere its partial pressure is abbreviated as Po2 = 21% of 760, or about 159 mmHg, nitrogen being 78% of the atmosphere would be 595 mmHg -> together they make up 99% of total pressure with CO2 making up the majority of the 1% gases are denser the lower they are, such that in space they would = 0mmHg Calculation of Po2 •with increasing altitude the total atmospheric pressure and the partial pressure of the constituent gases decrease •Denver, 5000 ft above sea level ~619 mmHg, and therefore PO2 is reduced to 619 X .21 = 130 mmHg, the peak of everest is only 42 mmHg •ever 33ft beneath sea level we see an increase in 1 atm -> at 33 ft below pressure is 2 X 760 = 1,520 mmHg, 66 ft below would by 3x inspired air contains variable amounts of moisture however by the time it has reached that lungs it is saturated with moisture (100% humidity) -> capacity to hold air is determined by temperature, so the temp of the respiratory zone is held constant at 37˚C, and its water vapor pressure is also held constant at 47 mmHg -> water vapor also plays a partial pressure to the total atmospheric pressure •due to the role of water vapor at sea level the PO2 of inspired oxygen is .21(760-47) = 150 mmHg compared to 159 mmHg as a result of gas exchange in the alveoli, there is an increase in the PCO2, while the PO2 is further diminished to about 105 mmHg from 150mmHg

Clinical application: urinary incontinence

uncontrolled urination due to loss of bladder control has many possible causes stress urinary incontinence -> result when urine leakage occurs due to increased abdominal pressure as during sneezing, coughing, and laughing seen in women when the pelvic floor no longer provides adequate support to the urethra due to childbirth or aging -> often treated with a sling surgery in which inserted mesh provides additional support for the urethra in men urinary incontinence occurs as a result of treatments for prostate cancer urgency incontinence involves uncontrolled contractions of the detrusor muscle that produce a great urge to urinate and leakage of a large volume of urine -> hallmark of a person with an overreactive bladder -> experience frequent urination and other symptoms urinary incontinence can be diagnosed by urodynamic testing including cystometric tests in which the bladder pressure and compliance are measured as the bladder is filled with warm water and subject is asked to say when the urge to urinate appears

Effects of Blood Po2 on ventilation

under normal conditions, blood Pco2 affects breathing only indirectly by influencing the chemoreceptor sensitivity to changes in Pco2 •chemoreceptor sensitivity to Pco2 is augmented by a low Po2 (why ventilation is increased at high altitude) and is decreased by a high Po2 •if the blood Po2 is raised by breathing 100% oxygen -> breath is held longer because response to increased Pco2 is blunted when blood Pco2 is held constant by experimental techniques, the Po2 of arterial blood must fall from 100mmHg to below 70 mmHg before ventilation is significantly stimulated this stimulation known as hypoxic drive is apparently due to a direct effect of Po2 on the carotid bodies -> the carotid bodies contain neuron-like glomus cells that can sense a drop in arterial Po2 from normal (100 -> 60-80 mmHg) -> glomus cells depolarize -> release neurotransmitter stimulating different afferent neurons of the carotid sinus nerve, a branch of the glossopharyngeal (IX cranial) nerve •carotid bodies respond to the oxygen dissolved in the plasma (measured by blood Po2) not oxygen bound to RBCs •the degree of hypoxemia (low blood oxygen) required to stimulate the carotid bodies does not normally occur at sea level and so the arterial Po2 does not normally exert this effect however there are interactions between the sensitivities of the carotid bodies to fall in Po2 and increase in Pco2 •hypoxia (low oxygen) -> promotes carotid bodies' responses to a rise in Pco2 and fall in pH •high altitudes with low Po2 -> carotid bodies are essential for ventilation to acclimatize to high altitude, where a beneficial hyperventilation occurs conversely, persistently elevated arterial Pco2 enhances the sensitivity of the carotid bodies to a fall in Po2 •breathing in response to lower Po2 is important in emphysema -> chemoreceptor response to elevated Pco2 is blunted -> results from increased secretion of bicarbonate by the choroid plexus buffering the fall in pH -> those impacted are stimulated to breath by hypoxic drive rather than elevated Pco2 •this can be dangerous if you were to give an O2 mask to someone with emphysema as the body would not respond to breathing stimili -> would require mechanical ventilation •over long period of time the hypoxic drive in those with emphysema can also become blunted

Clinical application: pregnancy tests

use monoclonal antibodies against the beta subunit of hCG hCG is produced not by the mother but rather the trophoblast embryonic cells -> test should be negative if not pregnant unless she took exogenous hCG to treat infertility false negative results occur when the test is performed too early because hCG doesn't reach detectable levels until implantation around day 12 -> due to time sperm can live in tract we can see false negatives for more than two weeks following intercourse