FINAL EXAM

• Plasma and Cellular Elements of Blood
• Hematopoiesis
• RBC Physiology
• Coagulation

• 92% water
• 7% proteins
• 1% organic mol (AA, glucose, lipids, N wastes), ions (Na+, K+, Cl-, H+, Ca2+), trace elements, vitamins, O2, and CO2

albumins *60% (prescence of proteins makes osmotic pressure higher; carriers)

• globulins (clotting, enzymes, antibodies, carriers)
• fibrinogen (essential to clotting) *30%
• transferrin (transports iron)

immunoglobulins (antibodies; secreted by specialized blood cells rather than by liver)

• Functions:
• clotting
• defense against foreign invaders
• carriers for steroid hormones, cholesterol, drugs, and iron
• act as hormones or enzymes

• RBCs (erythrocyes)
• WBCs (leukocytes)
• platelets (thrombocytes)

• have lost their nucleus by the time they enter the blood stream
• play key role in transporting O2 from lungs -> tissues
• CO2 from tissues -> lungs

shape creates greater surface area for fast diffusion

25% of blood cells being produced by marrow, have a longer life span

• only fully functional cells in circulation
• play key role in body's immune response
• defend against foregin invaders
• work is usually carried out in tissues rather than in circulatory system
• Five types of WBCs:
• lymphocytes *immunocytes

monocytes (in tissues: macrophages) *phagocytes

• neutrophils
• eosinophils *granulocytes
• basophils (mast cells)

Diapedesis: WBC leaves

Are replaced more frequently because they have a shorter life span, 75% of blood cells being produced by marrow

• lack a nucelus
• split off parent cell, megakaryocyte
• short lived, 10 days
• many nuclei
• contain granules filled with clotting proteins and cytokines
• activated when blood vessel wall damaged
• play a role in coagulation

• the synthesis of blood cells
• embryo forms clusters -> blood cells -> liver, spleen, and bone marrow produce -> liver and spleen dont produce after birth -> production continues in the marrow until age 5 -> continues to decrease as we age

• control hematopoiesis
• peptide proteins released from one cell that affect the growth or activity of another cell

• erythropoietin - controls RBC synthesis, hormone; but made on demand rather than stored in vesicles; produced in kidney cells
• CSF - made by endothelial and WBCs
• IL -vreleased by one WBC to act on another, role in immune system; mobilizes hematopoietic stem cells
• thrombopoietin - produced by liver, influences growth of megakaryocytes

• RBC production controlled by erythropoietin (EPO) and several cytokine
• hypoxia: low O2 levels in the tissues (HIF-1) stimulates EPO synthesis and release
• put more hemoglobin into circulation to carry O2
• EPO gene cloned in 1985 -> now available
• used in therapy, abuse in sport

• 4 subunits
• HbA- Adult
• HbF - Fetal; increased affinity to O2; pulls O2 from HbA (mother)
• Requires iron Fe from diet -> absorbed to small intestine by active transport -> transported in blood by transferrin -> RBC use Fe to make heme group of hemoglobin -> excess iron stored (liver) as ferritin -> bone marrow uses to make Hb -> liver metabolizes biliruben; execretes in bile -> metabolites execreted in urine or feces
• Vit B12; intrinsic factor to absorb
• HbS - sickle cell
• elevated biliruben levels in blood = jaundice, causes skin and white of the eyes to take on a yellow cast. normally occurs in newborns whos fetal Hb is being broken down and replaced with adult Hb; also liver disease causes jaundice, liver is unable to process or excrete biliruben

• Polycythemia vera- people in high altitudes, too many RBC, viscocity makes heart work harder, may be due to BM cancers
• Anemias-
• hemorrhagic: Fe deficiency; common in women
• hemolytic: due to genetic diseases or infections, autoimmune or drug induced, malaria
• pernicious: B12 deficiency or instrinsic factor lacking (stomach)
• renal: kidneys dont produce (EPO)

• abnormal hemoglobin
• crystallizes when it gives up its oxygen
• sickle cells become tangled with other sickle cells causing cells to jam and block blood flow in tissues
• creates tissue damage and pain from hypoxia
• NO being tested as treatment

• stopage of bleeding
• too little: hemophiliac -> bleed too much
• too much: thrombus/ emboli -> blood clots
• Three major steps -
• vasconstriction - vessels constrict; paracrines released by endothelium -> decreases blood flow and pressure in vessel
• platelet plug - temporary blockage of hole; platelets stick to exposed collagen -> releases cytokines -> released more platelets that stick to each other
• coagulation - clot formation seals hole until tissue is repaired; series of enzymatic reactions end in formation of fibrin protein fiber mesh that stabalize platelet plug

collagen exposure; all necessary factos present in blood; slower

Uses TF released by injured cells and a shortcut

Intrinsic/ Extrinsic pathways -> active Factor X -> prothrombin -> thrombin -> fibrinogen -> fibrin -> reinforces platelet plug -> clot

• as it forms it incorporates plasmin, the seeds of its own destruction
• Plasmin: enzyme from plasminogen, activated by thrombin, breaks down fibrin polymers into fibrin fragments (fibrinolysis) -> removes clot

• dissolve inappropriate clots
• enhance fibrinolysis
• t-PA: tissue plasminogen activator; dissolves clot faster
• *Vit K necessary for liver to make clotting proteins

• "blood thinner" prevent blood from clotting
• by blocking one or more steps in fibrin forming cascade
• ihhibit platelet adhesion -> plug prevention
• Ex. asprin -> inhibits plug, heparin -> inhibits thrombin, Protein C -> inhibits clotting factors V and VIII

• coagulation disorder
• coagulation cascade lacking or defective
• Hemophilia A, factor VIII deficiency, most common
• sex linked, ususally affects only males

• ratio of RBCs to plasma
• column of packed red cells is measured
• normal range of hematocrit 40-54% male 37-47% female

• structure and function of respiratory pumps
• gas exchange with blood
• role of surfactant and pressure differences on rate of exchange
• regulation of respiration

• O2 exchange: air -> blood, blood -> cells
• CO2 exchange: cells -> blood, blood -> air
• Regulation of body pH: retaining/ excreting CO2
• Protection of alveoli -> blood
• Vocalization

the pharynx, the larynx, then the trachea

• the exchange of air between the atomosphere and the lungs
• the exchange of O2 and CO2 between the lungs and blood
• the transport of O2 and CO2 by the blood
• the exchange of gases between blood and the cells

move mucus to the pharynx

• 3 upper airway functions -
• warming, humidifying, and filtering
• mucocilary escalator depends on secretion of watery saline - cystic fibrosis
• mucus
• H2O
• pseudostratified columnar epithelium
• goblet cells: secrete mucus
• alveoli: function is the exchange of gases between themselves and blood type II secrete surfactant: chemical mixes with thin fluid lining the alveoli to aid lungs as they expand during breathing

• pulmonary trunk; receives low-02 blood from R. ventricle -> divides into 2 pulmonary arteries -> 02 blood returns to L atrium via pulmonary veins
• high flow rate, but pulmonary BP is low
• distance shorter, resistance is low; R. ventricle doesnt have to pump as forcefully

• Dalton's: total P exerted by a misture of gases is the sum of P exerted by individual gases
• air we breath: N2 78%, 02 21%, H20/ vapors
• P @ sea level: 760 mmHg
• Boyle's: P1V1=P2V2
• gases move down pressure gradients

• N2 is important for divers
• come up too fast N2 bubbles in blood -> Nitrogen Narkosis

external respiration!

• air flows due to pressure gradients
• inspiration: contraction of diaphragm 60-75% volume change
• 25-40% due to external intercoastals and scalene muscles
• expiration: relaxation of inspiratory muscles
• elastic recoil of pleura and lung tissue reinforce muscle recoil
• passive unless forced -> internal intercoastals and abdominal muscles

• for pulmonary function tests
• measures lung volumes during ventilation

• lungs unable to expand and contract on their own
• during development intrapleural pressure becomes substomospheric; necessary to keep lungs inflated

• from aveolar type II cells
• detergent like complex of proteins and PL; disrupts cohesive forces between water molecules -> decreased surface tension -> decreased work of breathing

• compliance: ability of lungs to stretch
• low compliance in fibrotic lungs (and other lung diseases) and when not enough surfactant
• elasticity: ability to return to original shape
• low elasticity in case of emphysema due to destruction of elastic fibers
• normal lung is both compliant and elastic

• influences work of breathing
• determinant: airway diameter
• CO2: bronchodilation
• parasympathetic neurons: contricts
• no sympathetic neurons but Beta2 receptors: bronchodilation
• histamine: contriction

• heart efficiency? CO= HR x SV
• pulmonary ventilation: PV= RR x LV (tidal volume) 12x 500
• 150 ml anatomic dead space
• alveolar ventilation: RR x 350

• lung has collapsible capillaries -> reduced blood flow at rest in lung apex
• increased CO2 in exhaled air -> bronchodilation
• decreased 02 in ECF around pulmonary arterioles -> vasoconstriction of arteriole (blood diverted)

• Dissolve CO2 and 02 for transport
• Transport 02 - role of hemoglobin
• Transport CO2
• Regulate ventilation

• Ficks: diffusion rate surface rate x conc. gradient x mem. permeability\ membrane thickness
• diffusion is most rapid over short distances
• solubility of a gas depends on solubility of mol. in particular liquid and on pressure gradient and temperature

Total atmospheric pressure as sea level = 760 mmHg

• 21% 02 P02= 160 mmHg
• 78% N2 PN2= 593 mmHg

• gases flow from regions of higher partial pressure to regions of lower partial pressure.
• 02 moves from aveolar (100 mmHg) to capillaries (40 mmHg)
• P02 is lower in the cells 02 diffuses down its partial pressure gradient from plasma into cells
• PC02 is higher in tissues than in capillaries
• PC02 40 mmHg in aveoli 46 mmHg in tissues therefore the gradient causes C02 to diffuse out of the cells into the capillaries

• Diffusion rate decreases and you don't get enough 02
• main factor that affects 02 content of air is altitude
• low aveolar ventillation is know as hypoventillation
• increased airway resistance
• decreased lung compliance
• CNS depression

• emphysema: destruction of aveoli = less surface area for gas exchange
• fibrotic lung disease: thickened aveolar membrane slows gas exchange, loss of lung compliance may decrease aveolar ventilation
• pulmonary edema: fluid in interstitial space increases diffusion distance
• asthma: increased airway resistance, decreased aveolar ventilation

• aveolar P02 may be normal but respiratory membrane changes affect gas exchange
• increased membrane thickness = fibrotic lung disease
• decreased surface area = emphysema

• 98% carried by Hemoglobin (oxihemoglobin) -> transported inside RBCs
• rest is dissolved in plasma
• at the cells where where 02 is used and plasma P02 falls Hb gives up its 02
• we must have adequate amount of Hb in our blood to survive

• 20 mmHg exercising muscle 30%
• 40 mmHg normal resting cell 75%
• 100 mmHg normal of aveoli 98%

• Factors effecting:
• pH decreases
• temperature increases (cold = left shift -> gives off less 02 -> stronger affinity to Hb)
• PC02 increases
• HbF increases (left shift)

• 7% directly dissolved in plasma
• 70% transported as HC0- (bicarbonate) dissolved in plasma; acts as buffer; provides additional means of C02 transport from cells to lungs
• 23% bound to Hb
• excess C02 in blood = hypercapnia -> leads to acidosis, CNS depression and coma

stimuli- emotions and voluntary control -> higher brain centers -> limbic system -> medulla oblongata and pons -> somatic motor neurons for inspriation (effects scalenes, external intercoastals, diaphragm) or expiration (effects internal intercoastals, abdominals)

stimuli- C02 -> medullary chemoreceptors -> medulla OR carotid and aortic chemoreceptors -> afferent sensory neurons -> medulla

stimuli- 02 and pH -> carotid and aortic chemoreceptors -> afferent sensory neurons -> medulla oblongata or pons

• regulation of ECF volume and BP
• regulation of osmolarity
• maintenance of ion balance
• homeostatic regulation of pH
• excretion of wastes
• production of hormones

• Filtration
• Reabsorption
• Secretion
• Excretion

• Movement of fluid from blood to lumen nephron
• composition is like that of plasma - plasma proteins (water and dissolved solutes)
• once in the lumen, considered outside the body

• filtration takes place in the Renal Corpuscule
• 3 barriers:
• glomular capillary endothelium (fenestrated capillaries= large pores)
• basement membrane
• epithelium of bowmans capsule

• hydrostatic pressure in capillaries: blood pressure; filtration takes place along nearly the entire length of the glomerular capillaries
• colloid osmotic pressure: pressure gradient is due to the presence of proteins in the plasma
• hydrostatic pressure in bowman's capsule: presence of fluid in the capsule creates fluid pressure that opposes fluid movement into the capsule

• filtration takes place in the glomerulus of a nephron
• average GFR 180L/day, 60 times per day, 2.5 times per hour
• amount of fluid filtered into Bowman's capsule per unit of time
• influenced by: net filtration pressure (determined by renal blood flow and blood pressure) and the filtration coefficient (surface area of glomerular capillaries and permeablity of interface between the capillary and bowman's capsule)
• surface area of kidneys depends on how many functional nephrons

• GFR is constant over a wide range of blood pressures
• MAP remains between 80 mmHg and 180 mmHg, GFR averages 180L/day
• controlled by regulation of blood flow through the renal arterioles
• resistance on GFR increases in the afferent arteriole hydrostatic pressure decreases -> decrease in GFR
• resistance on GFR increases in the efferent arteriole hydrostatic pressure increases -> increase in GFR

• autoregulation: kidneys maintains a constant GFR with normal fluctuations in blood pressure
• protect the filtration barriers from high blood pressures that might damage them
• myogenic response- instrinsic ability of smooth muscle to respond to pressure changes
• tubuloglomerular- paracrine signaling mechanism through which changes in fluid flow through the loop of henle, influence GFR

• increased blood pressure -> smooth muscle in arteriole wall stretches -> stretch sensitive ion channels open -> muscle cells depolarize-> opens voltage gated Ca2+ channel -> smooth muscle contracts -> increases resistance to flow -> blood flow through arteriole deminishes -> decreases filtration pressure on glomerlus
• *a decrease in GFR helps the body conserve blood volume

GFR increases -> flow through tubules increases -> flow past macula densa increases -> paracrine from macula densa to afferent arteriole -> afferent arteriole constricts -> resistance in afferent arteriole increases -> hydrostatic pressure in glomerulus decreases -> GFR decreases

• reflex regulation: hormones and the ANS alter glomerular filtration by changing resistance in arterioles and altering filtration of coefficient
• neural control is mediated by sympathetic neurons that innervated afferent and efferent arterioles
• hormones also influence arteriolar resistance by acting as podocytes (change size of glomerular filtration slits- widen more surface area for filtration GFR increases) or mesangial cells (contraction changes the glomerular capillary surface area available for filtration

• more than 99% of the fluid entering the tubules must be reabsorbed into the blood as filtrate moves through the nephrons
• most takes place in proximal tubule, other in distal segments of nephrons
• allows kidneys to return ions and water to plasma to maintain homestasis
• clears foreign materials from plasma quickly
• filtering ions and water into the tubules simplifies their regulation

• Na+ reabsorbed by active transport
• Anion reabsorbed by electrochemical gradient
• water moves by osmosis following solute reabsorption
• urea/permeable solutes are reabsorbed by diffusion

• Na+ enters the cell through membrane proteins, moving down its electrochemical gradient
• Na+ is pumped out the basolateral side of the cell by the Na+-K+-ATPase

• Na+ moving down its electrochemical gradient using SGLT protein pulls glucose into the cell against its concentration gradient
• glucose diffuses out the basolateral side of the cell using GLUT protein
• Na+ is pumped out by Na+-K+ATPase

• renal transport can reach saturation; the transport rate at saturation is the transport maximum
• the plasma concentration at which glucose first appears in the urine
• specificity
• competition

• transfer of molecules from ECF into the lumen of the nephron
• depends mostly on membrane transport systems
• enables the nephron to enhance execretion of a substance active process, requires moving substrates against their concentration gradients
• 2nd route of entry into tubules for selected molecules
• mostly transepithelial transport; depends on secondary active transport mostly
• rapid removal of substances

• rate depends on the filtration rate and whether the substance is reabsorbed, secreted, or both
• excretion of H20, excess ions, nitrogenous waste, toxins, and other foreign molecules
• excretion = filtration - reabsorption + secretion
• kidneys clean or clear plasma of certain substances
• clearance= plasma volume completely cleared of that substance per minute

• GFR: is an indicator for overall kidney function
• clearance: non-invasive way to measure GFR (insulin/ creatine)
• substance is filtered and reabsorbed but not secreted the clearance rate is less than GFR
• substance is filtered and secreted but not reabsorbed the clearance rate is greater than GFR

• urine -> renal pelvis -> ureter -> bladder -> smooth muscle contractions
• urine is stored in bladder until released in micturition
• bladder can hold about 500 ml
• opening between bladder and urethra is closed by two rings of muscle called sphincters
• tonic stimulation from CNS maintains contraction of the external sphinctor except during urination

stretch receptors fire -> parasympathetic neurons fire; motor neuron stop firing -> smooth muscle contracts; internal sphinctor passively pulled open; external sphinctor relaxes

• symptoms when < 25% functional neurons
• causes: diabetes, HBP, kidney infections, chemical poisoning
• 75% of kidney destroyed for symptoms to occur
• *why you can donate kidneys
• CAPD- Continuous Ambulatory Peritoneal Dialysis
• *urea will come out by diffusion

• explain homeostasis of:
• water balance (ICF/ECF volumes)
• electrolyte balance (osmolarity)
• acid-base balance (pH)

decreased blood volume and pressure -> volume receptors in atria, carotid, and aortic baroreceptors -> increased ADH (vasopressin) cardiovascular system, behavior, or kidneys -> increase cardiac output/ vasocontriction, thirst causes increased water intake, increased ECF and ICF volume -> increased blood pressure OR conserve H20 to minimize further loss

increased blood volume and pressure -> volume receptors in atria, endocrine cells in atria, and carotid and aortic baroreceptors -> cardiovascular system, kidneys -> decrease cardiac output, increase salts and H20 in urine, decrease ECF and ICF volume -> decreased blood pressure

• kidneys maintain H20 balance by regulating urine concentration
• kidneys cannot replenish lost water, all they can do is conserve it

• when maintenence of homeostasis requires eliminating excess water, the kidneys produce copius amounts of dilute urine with an osmolarity as low as 50 mOsM
• removal of excess water in urine is know as diuresis
• drugs that promote the excretion of urine are called diuretics
• when kidneys conserve water the urine becomes concentrated
• kidneys control concentration by varying the amounts of water and Na+ reabsorbed in the distal tubule and collecting duct
• to produce dilute urine the kidney must reabsorb solute without allowing water to follow by osmosis
• reabsorption of varying amounts of H20 and Na+ established by Loop of Henle and Collecting duct (where kidneys create hyposmotic fluid)

• released from posterior pituitary
• controls water reabsorption by adding or removing water pores in the apical membrane
• vasopressin acts on target cells -> water pores inserted into the apical membrane -> water move out of lumen by osmosis
• collecting duct is impermeable to water without vasopressin
• aquaporin: water pores; AQP2- water channel regulated by vasopressin

• primary sign of diabetes mellitus is an elevated blood glucose concentration
• any additional nonreabsorbable solute that remains in the lumen forces additional water to be excreted causes osmotic diuresis
• osmotic diuresis in untreated diabetics causes
• polyuria: excessive urination and
• polydipsia: excessive thirst as a result of dehydration and high plasma osmolarity

• concentrated: presence of ADH- insertion of H20 pores
• maximal H20 permeability -> net H20 movement stops at equilibrium
• maximal vasopressin, the collecting duct is freely permeable to water, water leaves by osmosis and is carried away by the vasa recta capillaries
• dilute: no ADH, DCT and CD impermeable to H20
• osmolarity can plunge to 50 mOsM
• in the abscence of vasopressin, the collecting duct is impermeable to water and the urine is dilute

• key to kidneys ability to produce concentrated urine is the high osmolarity of the medullary interstitium
• leads to hyperosmotic IF in medulla
• hyposmotic fluid leaving LOH
• transfers water and solutes

• Na+ concentration affects plasma and ECF osmolarity
• normal 140 mOsM
• Na+ affects BP and ECF volume
• higher ECF would draw water from the cells shrinking them and disrupting normal cell function
• additon of NaCl raises osmolarity ->
• vasopression secretion (causes kidneys to conserve waster and concentrate urine) and thirst (prompts us to drink water
• increased salt and water intake increases ECF volume and BP -> triggers series of control pathways brings them back to normal

• regulates Na+ and K+ excretion in last 1/3 of DCT and CD
• increased aldosterone secretion -> increased Na+ absorption
• steroid hormone synthesized in the adrenal cortex
• secreted into the blood and transported on a protein carrier to its target
• primary target = P cells by simple diffusion
• low blood pressure stimulates aldosterone secretion
• aldosterone combines with cytoplasmic receptor -> hormone receptor complex initiates transcription in nucleus -> new protein channels and pumps are made -> aldosterone induced proteins modify existing proteins -> result is increased Na+ reabsorption and K+ secretion

• pH of a solution is a measurment of its H+ concentration
• the normal pH of the body is 7.4
• enzymes and membrane channels are particularly sensitive to pH because the function of these proteins depends on their shape
• pH too low- acidosis neurons become less excitable and CNS depression results - excrete H+ and reabsorb K+
• pH too high- alkalosis neurons become hyperexcitable, firing action potentials at the slightest signal - reabsorb H+ and excrete K+
• K+ imbalance associated with acid base imbalance
• renal transporter that moves K+ and H+ ions in an antiport fashion

• due to aveolar hypoventilation, C02 retention -> elevated plasma PC02
• respiratory depression, increased airway resistance, impaired gas exchange
• metabolic: due to gain of fixed acid or loss of bicarbonate
• lactic acidosis, ketoacidosis, diarrhea
• buffer capabilities exceeded once pH change appears in plasma

• Buffers: 1st defense, immediate response
• Ventilation: 2nd, can handle 75% of most pH disturbances
• Renal Regulation: of H+ and HC03-, final, slow but very effective

• due to aveolar hyperventilation in the absence of increased metabolic C02 production
• causes: anxiety, excessive artifical ventilation, aspirin toxicity, fever, high altitude
• compensation = renal, filtered bicarbonate which if reabsorbed could act as a buffer and increase pH more
• metabolic: due to loss of H+ into intracellular space
• vomiting, NG suction, antacid overdose
• compensation = rapid

• motility
• secretion
• digestion
• absorption

pepsin vs. trypsin pH optimum

pancreas: 99% exocrine -> bicarbonate (HC03-), enzymes (amylase), lipase, protease (trypsin/ chymotrypsin) 1% endocrine -> insulin/ glucagon (antagonists)

• 2 purposes: forward movement of food, and mechanical mixing (duodenum)
• GI smooth muscles contract spontaneously
• pacemaker cells depolarize -> generate slow wave potentials
• APs spread throughout longitudinal muscles (gap junctions) -> wave of contraction
• parasympathetic stimulates GI tract
• most digestion occurs in small intestine
• cycles of smooth muscle contraction and relaxation are associated with spontaneous cycles of depolarization and repolarization = slow wave potentials
• slow wave potentials reach threshold -> voltage gated Ca2+ channels in the muscle fiber open -> Ca2+ enters -> cell fires action potential(s) -> depolarization result of Ca2+ entering cell -> initiates muscle contraction

• tonic contractions: sustained for minutes or hours occur in smooth muscle sphinctors and in the anterior portion of the stomach
• phasic contractions: contraction-relaxation cycles lasting only a few seconds occur in posterior region of the stomach and in small intestine
• peristaltic contractions: push a bolus forward
• occurs mainly in esophagus
• influenced by hormones, paracrine signals, and ANS
• segmental contractions: segments of intestine alternately contract and relax- lead to mixing
• occur randomly along the intestine or at regular intervals

• 9 L of fluid a day
• 7 L composed of water and ions -> secreted into lumen of tract
• Acid: parietal cells secrete HCl into the lumen of the stomach; 1-3 L per day in stomach; pH as low as 1
• bicarbonate is absorbed in blood -> buffering action makes blood leaving stomach less acidic -> "alkaline tide"
• bicarbonate: some secreted by duodenal cells, most from pancreas
• requires high levels of carbonic anhydrase
• acinar cells secrete digestive enzymes
• duct cells secrete NaHC03
• digestive enzymes: secreted by salivary glands or pancreas or by epithelial cells in small intestine
• synthesized on rough ER packaged by GC -> vesicles -> stored in the cell
• secreted in an inactive proenzyme (zymogens); must be activated in GI lumen
• mucus: made in special exocrine cells (mucous cells) in stomach and goblet cells in intestine (10-24%)
• salivary glands also secrete mucus
• saliva: secreted by salivary glands
• controlled by ANS
• parasympathetic innervation primary stimulus
• bile: secreted from hepatocytes or liver cells
• bile salts (emulsifiers- fat breakdown), bile pigments (bilirubin), cholesterol
• secreted into hepatic ducts -> gall bladder where its stored -> during a meal sends bile to duodenum

• mechanical breakdown aids enzymatic breakdown
• enzymatic breakdown converts macromolecules into absorbable units
• optimal pH of enzymes indicates location of activity

• small intestine absorbs most nutrients
• fats absorbed into lacteals (lymph capillaries)
• everything else absorbed into blood
• alcohol and aspirin across gastric epithelium
• additional H20, ions, some vitamins absorbed in large intestine

• complex COH and disaccharides must be digested if they are to be absorbed
• starch and glycogen broken down by enzyme amylase
• glucose and galactose absorption uses transporters identical SGLT and GLUT2
• fructose is not Na+ dependant; moves across apical membrane by facilitated diffusion on GLUT5 and across basolateral membrane by GLUT2

• cannot absorb lactose
• lactose left in GI tract
• osmotic diarrhea, polydipsia, polyurea

• genetic
• 2nd most common cause of cancer deaths
• cellulose (indigestible) = fiber, roughage
• roughage in diet helps food move through; less exposure to carcinogens that sit in body and mutate
• trypsin -> digests proteins

• plant proteins are least digestible
• 30-60% of protein found in GI lumen is from dead sloughing cells
• enzymes for protein digestion: endopeptidases (proteases) and exopeptidases
• proteases: attack peptide bonds in the interior of the aa chain, break a long chain into fragments; secreted as inactive proenzymes; ex- pepsin (stomach), trypsin, and chymotrypsin (pancreas)
• exopeptidases: chop off at ends; ex- carboxypeptidase (pancreas)
• proteins absorbed as free AA, dipeptides, and tripeptides
• absorption of proteins can lead to food allergies (gluten)
• drug companies develop indigestible protein/ peptide drugs (modified vasopressin)

• 90% of our fat calories come from triglycerides
• carried out by lipases -> triglycerides -> monoglyceride + 2 free FA
• fats form large clumps of chyme (hard to digest)
• phospholipids are digested by pancreatic phospholipase
• liver secretes bile salts into small intestine to increase the surface area available for digestion
• requires colipase secreted by pancreas; displaces some bile salts -> form micelles
• many fats absorbed by simple diffusion

• fat-soluble vitamins (A,D,E,K) are absorbed in small intestine along with fats
• the water soluble vitamins (C,B) are absorbed by mediated transport
• B12 transporter only found in ileum; only recognizes B12 with intrinsic factor secreted by stomach
• B12 deficiency: pernicious anemia
• mineral absorption occurs by active transport
• iron ingested as heme iron- more readily absorbed by endocytosis
• Fe2+ absorbed by apical cotransport with H+ on a protein
• iron uptake is regulated by hepcidin secreted by liver
• Ca2+ absorption in the gut - passive

• mostly in small intestine, some in colon
• enterocytes (small intestine) and colonocytes absorb Na+ using 3 membrane proteins - Na+ channels, Na+Cl- symporter, and NHE Na+-H+ exchanger
• in small intestine absorption takes place through SGLT and Na+-amino acid transporters
• H20 follows

• Chemical and mechanical digestion begins in the mouth
• salivary secretion under ANS control
• mechanical digetion: chewing
• chemical digestion: salivary amylase, and lysozyme
• swallowing reflex: deglutition

• 3 functions of stomach:
• storage
• digestion
• protection
• bicarbonate creates a chemical buffer barrier underlying the mucus

• bicarbonate neutralizes gastic acid
• activation of pancreatic zymogens
• digestive enzymes -> enteropeptidases
• goblet cells secrete mucus for protection and lubrication
• most fluid absorbed in small intestine
• diarrhea can cause dehydration

• protection from disease causing invaders
• removal of dead/ damaged tissues and cells
• recognition and removal of abnormal cells

• pathogen: bacteria, viruses, fungi, protozoans, parasites
• antigen: substances that trigger the body's immune response and can react with products of that response
• antibody: proteins secreted by certain immune cells, bind to antigens and make them more visible to the immune system
• innate immunity: present from birth and is the body's nonspecific immune response to invasion
• acquired immunity: is directed a specific invaders and for this reason is the body's specific immune response

• Basophils: (mast cells) rare -> release chemicals that mediate inflammation and allergic responses
• Neutrophils: 50-70% ingest and destroy invaders
• Eosinophils: (cytotoxic) 1-3% destroy invaders (antibody coated parasites)
• Granulocytes^
• Monocytes: (macrophages in tissue) 1-6% ingest and destroy invaders; antigen presentation
• 3^Phagocytes
• Lymphocytes: (plasma cells) B (plasma/memory cells) T (cytotoxic T/ helper T cells) NK cells; specific responses to invaders, including antibody production
• Dendritic Cells: (langerhans) (cytotoxic) recognize pathogens and activate other immune cells by antigen presentation
• 3^antigen presenting

• Innate: nonspecific
• hinders pathogen entry and dispersion through body
• strengthens specific immune system
• Acquired: specific
• inactivation of specific pathogen
• must be primed first
• specific resistance = immunity

• consists of patrolling and stationary leukocytes that attack and destroy invaders
• clears the infection or contains it until acquired immune response is activated
• physical barriers include skin, protective mucous lining, ciliated epithelium, acidity of stomach, lysozyme- enzyme with antibacterial activity
• phagocytosis: macrophages, neutrophils, and NK cell attack and destroy pathogens/ foreign mol. nonspecifically
• attracted to areas of invasion by chemical signals -- chemotaxis (bacterial toxins or cell wall components, activated leukocytes)
• macrophages toll-like receptors activate the cell to secrete inflammatory cytokines
• phagocytes recognize bacteria and produce antibodies against them "tagged"
• opsonins: antibodies that tag bacteria with plasma proteins; convert unrecognizable particles into "food" for phagocytes

• recognize virus infected cells and induce them to commit apoptosis before it can replicate
• also attack tumor cells
• secrete interferons

• inflammatory response is created when activated tissue macrophages release cytokines
• chemicals attract other immune cells, increase capillary permeability, cause fever
• histamine: found in mast cells; active mol that helps initiate inflammatory response when mast cells degranulate
• bring more leukocytes to the injury site
• opens pores in capillaries causing swelling or edema
• increases blood flow to the area, making it hot, red, and swollen
• antihistamines: block the action of histamine at its receptor
• histamine + mast cells, lipid mediators responsible to anaphylactic shock and bronchodilation

• IL-1 is secreted by activated macrophages and other immune cells; role is to mediate the inflammatory response
• alters blood vessel endothelium to ease passage of WBCs and proteins
• stimulate production of acute-phase proteins by liver
• induces fever
• stimulates cytokine and endocrine secretion

• has same vasodilation effects as histamine
• stimulates pain receptors
• pain draws brains attention to injury

• act as opsonins
• chemical attractants for leukocytes
• agents that cause mast cell degranulation-
• MAC: complement insert themselves into the membrane of pathogen -> creating pore -> water and ions enter the cell -> cell swells and lyses

• antigen specific responses
• lymphocytes: B cell -> plasma cells (secrete antibodies), T cells -> attack and destroy or regulate cells, NK cells -> attack and destroy
• lymphocytes release additional cytokines to enhance inflammatory response
• active immunity: occurs when body is exposed to pathogen and produces own antibodies. can happen naturally or artificially (vaccinations) ; makes memory cells
• passive immunity: occurs when we acquire antibodies made by another animal. ex. mother to infant, & injections containing antibodies ; no memory

• B lymphocytes activated -> become plasma cells; antibodies that attack that antigen -> memory cells; 2nd immune response to same antigen = much faster
• T lymphocytes -> direct attack -> effector cell or memory cell

• IgG: make up 75% of plasma antibody in adults; activate complement
• IgA: found in external secretions - saliva, tears, mucous, breast milk; disable pathogens before they reach the internal environment
• IgE: allergic responses - binds with mast cell and antigen, mast cell degranulates -> release histamine
• IgM: on surface of B cells; associated with primary immune responses and react to blood group antigens; activate complement
• IgD: appear on surface of B cells; role is unclear

• act as opsonins -> coat antigens, facilitate recognition and phaogocytosis
• make antigens clump -> enhances phagocytosis
• inactivate bacterial toxins
• activate complement -> cell swell and lyse
• activate mast cells -> mast cell degranulate -> release histamine -> inflammatory response
• activates immune cells

• encoded with specific set of genes
• every nucleated cell of the body has MHC on its membrane
• "silverspoon" that feeds T Cells
• T Cells cannot recognize free antigen without MHC present
• MHC Class I- found on surface of all nucleated cells - used to present peptides from intracellular invaders
• T cell recognizes cell with MHC I and kills it
• CTL recognizes MHC I
• MHC Class II- found on surface of antigen presenting cells and B cells
• T helper cells recognize MHC II creates immune response

• CD8 or TK
• attack and destroy cells displaying MHC I -ag complexes

T cell recognizes virus infected cell with MHC I ->release perforin molecules create protein channels in target cell membrane -> granzymes enter through perforin channels -> activate an enzyme cascade that triggers apoptosis in target cell

• activates complement system -> chemical signals (chemotaxis) attract leukocytes -> opsonins; enhance phagocytosis -> degranulation of mast cells -> secrete histamine (increase permeability; inflammatory response) -> formation of MAC (cells swell and lyse)
• phagocytosis -> if bacteria are not encapsulated macrophage can begin ingesting if they are antibodies must coat before ingested (opsonization)

macrophage ingests virus -> macrophage presents antigen fragment (MHC II) -> secretes cytokines (inflammatory response/ interferon induce host cell to produce antiviral proteins) and activate helper T cells -> activates B cells and cytotoxic t cells -> b cells become plasma cells and secrete antibodies -> cytotoxic t cells attack MHC I viral infected host cell -> apoptosis

• 1st exposure: allergen ingested and processed by APC (MHC II) -> APC activates helper T cell -> activates B cell (memory b and t cells retain memory of exposure to allergen) -> becomes plasma cell -> secretes antibodies
• 2nd exposure: memory activates T cells, antibodies secreted -> cytokines, complement proteins, degranulation of mast cell -> inflammation response

• most severe IgE mediated allergic reaction
• mast cells -> histamine
• speed up heart, hives, bronchocontriction, BP increased
• widespread vasodilation crashes BP

• Type A: anti B antibodies in plasma
• Type B: anti A antibodies in plasma
• Type O: both anti A and anti B antibodies in plama
• Type AB: have no antibodies to A or B antigens

• when self tolerance fails the body makes antibodies against its own components through T cell- activated B lymphocytes
• autoimmune disease

• stress alters immune system function
• pathogen -> immune cells -> endocrine cells -> target cell
• stress -> brain -> endocrine cell -> target cell

• human chromosomes
• gametogenesis
• fertilization
• early development
• paturition

• 44 autosomes
• 2 sex chromosomes (X&Y)
• XX female XY male

• starts in urtero- resumes at puberty
• mitosis: germ cell proliferation
• meiosis: DNA replicates but no cell division
• 1st meiotic division: primary gamete divides into two secondary gametes
• 2nd meiotic division: secondary gamete divides
• fertilization (if not fertilized egg passes out of body) -> zygote
• women are born with all the eggs, oocytes they will ever have
• men manufacture sperm continuously from the time they reach reproductive maturity

• XO: Turner Syndrome
• XXX: Triple-X Syndrome
• XXY: Kilinefelter Syndrome
• XYY: Jacob Syndrome
• Trisomy 21: Down Syndrome

• XO
• broad, webbed neck, stature reduced, edema in ankles and wrists
• relatively normal lives but no functional ovaries
• 1 in 2,000 births

• XXY
• usually normal- may be tall and have small testes
• infertile
• 1 in 1,500 males

• GnRH (hypothalamus) controls secretion of FSH and LH (anterior pituitary) -> act on gonads
• FSH is required along with sex hormones to maintain gametogenesis
• LH works primarily on endocrine cells, stimulating production of sex hormones
• estrogen alternates between + and - feedback
• lower estrogen have - feedback effect
• estrogen rise rapidly to a threshold or above for at least 36 hrs feedback changes from - to + LH is stimulated
• intersitial cells produce androgens

• in males LH is called ICSH
• seminiferous tubules: site of sperm production
• has spermatogonia and sertoli cells
• adjacent sertoli cells are linked together by tight junctions that form an additional barrier between the lumen of the tubule and the intersitial fluid outside
• spermatogenesis: sperm production
• sertoli cells: secrete proteins regulate sperm development; nourish spermatagonia
• leydig cells: secrete testosterone; also convert it to estradiol LH target

• female humans produce gametes in monthly cycles
• 3 phases-
• follicular phase: growth in ovary 10days - 3wks
• ovulation: one or more follicles have ripened; ovary released oocyte(s) during ovulation
• luteal phase: corpus luteum secretes hormones that continue the preparations for pregnancy; if pregnancy does not occur the corpus luteum ceases to function after about 2wks; ovarian cycle begins again
• changes in endometrial lining-
• menses: ovary corresponds to menstrual bleeding from the uterus
• proliferative phase: endometrium adds a new layer of cells in anticipation of pregnancy
• secretory phase: hormones from the corpus luteum convert the thickened endometrium into secretory structure; no pregnancy = loss in layers of secretory endometrium during menstruation

• GnRH from hypothalamus
• FSH and LH from anterior pituitary
• estrogen, progesterone, inhibin, AMH from ovary
• estrogen dominant in follicular phase
• ovulation is triggered by surges of FSH and LH
• progesterone is dominant in luteal phase (estrogen is also present)

• erection: parasympathetic activation, sympathetic inhibition; NO brings blood -> penis
• ejaculation: sympathetic activation of duct system smooth muscle
• erectile dysfuction: stress and age; physiological, hormonal, neural, vascular insufficiency

• takes place in the distal part of the fallopian tube
• of the millions of sperm only about 100 make it
• to fertilize the egg the sperm must penetrate both an outer layer of granulosa cells and zona pellucida
• to get past barriers sperm release powerful enzymes that dissolve cell junction and zona pellucida
• the first sperm to reach the egg finds sperm binding receptors on egg membrane and fuses membranes
• the sperm nucleus then sinks into eggs cytoplasm
• once the egg is fertilized it becomes a zygote and undergoes mitotic division

• zygote moves from distal fallopian tube -> uterine cavity over 3-4 days
• under influence of progesterone
• implantation on uterine wall - 7days after fertilization
• ovulation -> fertilization 1 -> cell division 2-4 -> blastocyte reaches uterus 4-5 -> blastocyte implants 5-9

• peptide hormone secreted by chorionic villi and developing placenta
• structurally related to LH and binds to LH receptors
• under the influence of hCG the corpus luteum keeps producing progesterone to keep endometrium intact
• 7th week placenta takes over progesterone production and corpus luteum degenerates
• hCG production by placenta peaks at 3 months then diminishes
• hCG also stimulates testosterone by developing testes in male fetuses
• chemical detected by pregnancy tests

• paturition = birthing process:
• fetus is normally head down -> rhythmic uterine contractions push head against softened cervix stretching and dialating it -> once the cervix is fully dialated and stretched the uterine contractions push fetus out through the vagina -> placenta detaches from the uterine wall and is expelled
• 38-40 weeks of gestation
• initiation of postive loop requires a uterus that is ready to respond to these stimuli
• fetus drops lower in uterus -> cervical stretch -> uterine contractions -> cervical stretch -> oxytocin from posterior pituitary prostagladins from uterine wall -> uterine contractions