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Blood:
- Plasma and Cellular Elements of Blood
- Hematopoiesis
- RBC Physiology
- Coagulation
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Plasma:
- 92% water
- 7% proteins
- 1% organic mol (AA, glucose, lipids, N wastes), ions (Na+, K+, Cl-, H+, Ca2+), trace elements, vitamins, O2, and CO2
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Plasma Proteins:
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
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Cellular Elements:
- RBCs (erythrocyes)
- WBCs (leukocytes)
- platelets (thrombocytes)
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RBCs:
- 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
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WBCs:
- 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
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Platelets:
- 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
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Hematopoiesis:
- 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
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Cytokines:
- 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
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Erythropoiesis:
- 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
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Hemoglobin:
- 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
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RBC Disorders:
- 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)
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Sickle Cell Anemia:
- 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
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Hemostasis:
- 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
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Instrinsic Pathway:
collagen exposure; all necessary factos present in blood; slower
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Extrinsic Pathway:
Uses TF released by injured cells and a shortcut
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Common Coagulation Pathway:
Intrinsic/ Extrinsic pathways -> active Factor X -> prothrombin -> thrombin -> fibrinogen -> fibrin -> reinforces platelet plug -> clot
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Structure of Blood 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
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Clot Busters:
- dissolve inappropriate clots
- enhance fibrinolysis
- t-PA: tissue plasminogen activator; dissolves clot faster
- *Vit K necessary for liver to make clotting proteins
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Anticoagulants:
- "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
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Hemophilia:
- coagulation disorder
- coagulation cascade lacking or defective
- Hemophilia A, factor VIII deficiency, most common
- sex linked, ususally affects only males
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Hematocrit:
- ratio of RBCs to plasma
- column of packed red cells is measured
- normal range of hematocrit 40-54% male 37-47% female
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Mechanics of Breathing:
- structure and function of respiratory pumps
- gas exchange with blood
- role of surfactant and pressure differences on rate of exchange
- regulation of respiration
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Functions of Respiratory System:
- O2 exchange: air -> blood, blood -> cells
- CO2 exchange: cells -> blood, blood -> air
- Regulation of body pH: retaining/ excreting CO2
- Protection of alveoli -> blood
- Vocalization
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On its way to the lungs, air passes through
the pharynx, the larynx, then the trachea
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External Respiration:
- 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
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The ciliated epithelium of the trachea and bronchi helps:
move mucus to the pharynx
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The Airways:
- 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
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Pulmonary Circulation:
- 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
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Gas Laws:
- 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
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Bends:
- N2 is important for divers
- come up too fast N2 bubbles in blood -> Nitrogen Narkosis
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Exchange of gases between lung and lung capillaries:
external respiration!
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Ventillation:
- 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
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Spirometry:
- for pulmonary function tests
- measures lung volumes during ventilation
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Aveolar and Intrapleural Pressures:
- lungs unable to expand and contract on their own
- during development intrapleural pressure becomes substomospheric; necessary to keep lungs inflated
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Surfactant:
- 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
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Lung Compliance and Elastance:
- 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
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Airway Resistance:
- influences work of breathing
- determinant: airway diameter
- CO2: bronchodilation
- parasympathetic neurons: contricts
- no sympathetic neurons but Beta2 receptors: bronchodilation
- histamine: contriction
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Efficiency of Breathing: Rate and Depth
- 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
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Matching Ventilation with Aveolar Blood Flow:
- 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)
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Gas Exchange and Transport:
- Dissolve CO2 and 02 for transport
- Transport 02 - role of hemoglobin
- Transport CO2
- Regulate ventilation
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Diffusion and Solubility of Gases:
- 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
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Review Dalton's Law:
Total atmospheric pressure as sea level = 760 mmHg
- 21% 02 P02= 160 mmHg
- 78% N2 PN2= 593 mmHg
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Gas Exchange in Lungs and Tissues:
- 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
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Lower Aveolar P02:
- 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
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Pathological Conditions that Reduce Aveolar Ventilation:
- 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
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Aveolar Membrane Changes:
- aveolar P02 may be normal but respiratory membrane changes affect gas exchange
- increased membrane thickness = fibrotic lung disease
- decreased surface area = emphysema
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Oxygen Transport in Blood:
- 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
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02-Hb Dissociation Curve:
- 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)
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C02 Transport in Blood:
- 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
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Regulation of Ventilation:
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
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The Kidneys:
- regulation of ECF volume and BP
- regulation of osmolarity
- maintenance of ion balance
- homeostatic regulation of pH
- excretion of wastes
- production of hormones
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Processes of Urinary System:
- Filtration
- Reabsorption
- Secretion
- Excretion
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Filtration:
- 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
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Renal Corpuscule: Passage across 3 barriers
- filtration takes place in the Renal Corpuscule
- 3 barriers:
- glomular capillary endothelium (fenestrated capillaries= large pores)
- basement membrane
- epithelium of bowmans capsule
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3 Types of Pressures Influence Filtration:
- 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
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Glomerular Filtration Rate (GFR):
- 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
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GFR Closely regulated:
- 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
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GFR Regulation:
- 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
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Myogenic Response:
- 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
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Tubuloglomerular Feedback:
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
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GFR Regulation:
- 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
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Reabsorption:
- 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
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Reabsorption may be active or passive:
- Na+ reabsorbed by active transport
- Anion reabsorbed by electrochemical gradient
- water moves by osmosis following solute reabsorption
- urea/permeable solutes are reabsorbed by diffusion
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Na+ reabsorption in the proximal tubule:
- 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
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Na+-linked glucose reabsorption in the proximal tubule:
- 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
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Characteristics of Renal Transport:
- 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
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Secretion:
- 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
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Excretion:
- 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
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Clinical importance of GFR and Clearance:
- 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
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Micturition:
- 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
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Renal Failure:
- 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
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Fluid and Electrolyte Balance:
- explain homeostasis of:
- water balance (ICF/ECF volumes)
- electrolyte balance (osmolarity)
- acid-base balance (pH)
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Body's Integrated Responses to Changes in Blood Volume and Pressure:
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
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Water Balance:
- kidneys maintain H20 balance by regulating urine concentration
- kidneys cannot replenish lost water, all they can do is conserve it
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Renal Medulla Creates Concentrated Urine:
- 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)
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ADH- Vasopressin:
- 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
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Diabetes Mellitus:
- 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
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Concentrated Vs. Dilute Urine:
- 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
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Loop of Henle- Countercurrent Multiplier:
- 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
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Na+ Balance and ECF Volume:
- 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
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Aldosterone:
- 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
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Acid-Base Balance:
- 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
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Acidosis:
- 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
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3 Mechanisms for Regulating pH Changes:
- 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
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Alkalosis:
- 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
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Digestion:
- 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)
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Motility:
- 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
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Different Patterns of 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
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Secretion:
- 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
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Digestion Overview:
- mechanical breakdown aids enzymatic breakdown
- enzymatic breakdown converts macromolecules into absorbable units
- optimal pH of enzymes indicates location of activity
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Absorption:
- 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
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COH Digestion and Absorption:
- 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
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Lactose Intolerance:
- cannot absorb lactose
- lactose left in GI tract
- osmotic diarrhea, polydipsia, polyurea
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Colon Cancer:
- 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
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Protein Digestion and Absorption:
- 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)
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Fat Digestion:
- 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
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Vitamin and Mineral Absorption:
- 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
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Absorption of H20 and Na+:
- 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
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Cephalic Phase:
- 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
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Gastric Phase:
- 3 functions of stomach:
- storage
- digestion
- protection
- bicarbonate creates a chemical buffer barrier underlying the mucus
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Intestinal Phase:
- 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
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The Immune System:
- protection from disease causing invaders
- removal of dead/ damaged tissues and cells
- recognition and removal of abnormal cells
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Vocabulary:
- 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
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Leukocytes:
- 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
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Immune Response:
- 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
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