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• When kidney cells become hypoxic O2 sensitive enzymes can not carry out function
of degrading HIF (hypoxia inducible factor) HIF accumulates and accelerates
synthesis and release of EPO
• Too many erythrocytes or too much O2 decreases EPO production
◦ Dietary requirements- raw materials required include amino acids, lipids, carbohydrates,
IRON, B vitamins also used for DNA production
• Destruction of Erythrocytes
◦ Lifespan 100-120 days
◦ Erythrocytes become fragmented with age and get trapped in small circulatory channels,
often the spleen
◦ Macrophages engulf old erythrocyte, haemoglobin separates and iron is recycled. Protein is
recycled into amino acids and heme group is degraded to bilirubin which is picked up by the
liver and secreted as bile
• Erythrocyte disorders
• Anemias- blood O2 carrying capacity is too low to support normals metabolism (3 categories:
blood loss, not enough blood cells produced, too many RBCs destroyed)
◦ Sickle cell anemia- sickle cell erythrocyte results from a single amino acid change in the
beta chain of haemoglobin, causes beta chains to link together under low O2 conditions,
forming stiff, spiky rods that rupture easily and can clog blood vessels
• Polycythemias- abnormally high amount of erythrocytes causing blood to become too viscous.
◦ Blood doping is artificially induced polycythemia
1% Buffy Coat (leukocytes and platelets)
• Platelets- megakaryocyte cell fragments
◦ Formation regulated by thromopoietin
• Leukocytes- the only true blood cells
◦ Immune functions
◦ 2 groups
▪ Granulocytes (functionally phagocytes)- includes neutrophils (active phagocytes),
eosinophils (attack parasitic worms and increase during allergic reaction) and basophils
(contain histamine, enhance inflammatory response)
▪ Agranulocytes (lack visible granules)- includes lymphocytes (immune cells) and
monocytes (differentiate into macrophages)
◦ Leuokopoiesis- directed by colony- stimulating factors and interleukins released by
supporting cells of the red bone marrow and mature WBCs
◦ Homeostatic imbalance includes leukaemias and mononucleosis
Hemostasis
3 Stages of Hemostasis
1) Vascular spasm- vasonconstriction, a strongly constricted artery can reduce blood loss for 20-30
minutes
2) Platelet plug formation- aggregation occurs, forming a plug that temporarily seals blood vessel
wall
Von Willenbrand factor stabilizes bound platelets forming a bridge between platelets and collagen
Adenosine diphosphate- aggregation agent that causes more platelets to stick to the the area
Serotonin and thromboxane A2- enhance vascular spasm and platelet aggregation
3) Coagulation- reinforcing platelet plug with fibrin threads that act as molecular glue which is
effective in sealing larger breaks
Process involving procoagulants turns blood to a gel
Clot Retraction
Platelets contain actin myosin, as they contract they pull on surrounding fibrin strands, squeezing
serum from the mass, compacting the clots and drawing ruptured edges closer
As this is occuring the vessel is healing
Fibronolysis- removes unneeded clots when healing has occurred
Plasmin- produced when plasminogen is activated, destroys the clot (Begins within two days and
continues until is gone)
Hemostatic Imbalance
1) Thromboembolic Disorders
Thrombus- clot that develops and persists in unbroken vessel
Embolus- clot that breaks away and begins circulation in the blood
Anticoagulant drugs include aspirin, heparin and warfarin, dabigatran is an alternative to warfarin
2) Bleeding disorders
Commonly caused by platelet deficiency and deficits of some clotting factors
Thrombocytopenia- deficiency of platelets
Impaired liver function can cause severe bleeding as liver is unable to synthesize clotting factors
Hemophilias- several hereditary bleeding disorders that have similar signs and symptoms
3) Disseminated Intravascular Coagulation
Widespread clotting in intact vessels, residual blood becomes unable to clot which can lead to blockage
and severe bleeding
Blood Typing
• Blood group is based on agglitinogen (antigen) present on red blood cell membrane
Genotype Phenotype Antigens on Serum Antibodies
Erythrocytes (Isohemaggliutinogens)
(Agglutinogen)
AA or AO A A Anti- B
BB or BO B B Anti- A
AB AB (Universal A and B None
recipient and least
common)
OO O (Universal donor None Anti-A and Anti-B
and most common) (Causes transfusion
reaction)
Bombay Phenotype- Rare blood type where individual with A, B, or AB group will appear as O
Cross matching tests- Tests whether recipient's serum will agglutinate donor's RBCs or vice versa
Antigen- Anything the body perceives as foreign, generates an immune response
Blood Loss
Losing 15-30% of blood causes pallor and weakness
Losing 30%+ causes severe shock and can be fatal
Whole blood transfusions are used when blood loss is substantial
Packed red cells- used in other cases and are preferred for restoring O2 capacity
RH Blood Groups
• 52 Rh agglutinogens called Rh factors (common ones are C,D,E)
• Haemoltyic disease of a newborn
◦ The body of Rh- mothers carrying second Rh+ baby can cause a reaction against the baby
with antibodies, leads to severe clotting and can caused erythroblastosis fetalis
◦ Treatment involves injecting the mother with Rhogam to prevent a reaction
Heart Chambers
• 2 atria
◦ Right atrium
◦ Left atrium
◦ Blood enters right atrium via 3 veins
▪ Superior vena cava- returns blood from body areas superior to diaphragm
▪ Inferior vena cava- returns blood fro body areas below diaphragm
Valves
• 2 AV Valves
◦ One at each atria-ventricular junction
◦ Open in relaxation, closed in contraction, prevents backflow
◦ Right AV valve- tricuspid (3 cusps)
◦ Left AV valve- bicuspid (2 cusps)
• 2 SL Valves
◦ Guard bases of large arteries issuing from ventricles
◦ Aortic semilunar valves
◦ Pulmonary semilunar valves
◦ Open in contraction, closed in relaxation, prevents backflow
◦ Each have 3 cusps
• There are no valves guarding entrance to venae cavae and pulmonary veins, some blood does
spurt back, but it is minimal
• Insufficient values force heart to repump the same blood continuously
• Valvular stenosis- valve become stiff, constricting the opening, compels heart to contract more
forcefully
Coronary Circulation
• Myocardium is too thick to diffuse nutrients, heart gets nourishment through coronary
circulation
• Coronary arteries arise from base of aorta and encircle heart in coronary sulcus
◦ Left coronary artery runs toward left side of heart, divides into 2 major branches
▪ Anterior interventricular artery- supplies blood to interventricular septum and anterior
walls of both ventricles
▪ Cirumflux artery- supplies left atrium and posterior walls of left ventricle
◦ Right coronary artery- courses to right side of heart, gives rise to 2 branches
▪ Right marginal artery- serves myocardium of lateral side of heart
▪ Posterior interventricular artery- runs to the heart apex, supplies posterior ventricular
walls
◦ Blood delivery to the myocardium occurs during relaxation
• Coronary veins- paths roughly follow arteries, veins join to form coronary sinus which empties
blood into right atrium
• Angina pectoris- thoracic pain caused by fleeting deficiency in blood delivery to myocardium,
can lead to MI
Myocardial Contraction
• Myocardial cells at rest usually -85mv
• Automaticity/ autorhythmicity- some cardiac muscle is self excitable
• Events of Contraction
◦ Depolarization
◦ Plateau phase
◦ Re-polarization
• Energy Requirements: Cardiac muscle is abundant in mitochondria and is dependant on aerobic
respiration
• Heart Physiology
◦ Ability of heart to contract is intrinsic, however heart is supplied with autonomic nerve
fibers that can alter the basic rhythm
▪ Intrinsic conduction system – activity of the heart is a result of gap junctions and
conduction system which consists of noncontractile cardiac cells specialized to initiate
and distribute impulses
• Conduction system consists of SA and AV nodes, AV bundle and bundle branches
and subendocardial conducting network
◦ SA node has the fastest response to depolarization and sets the sinus rhythm
• Unstimulated contractile cells maintain a stable resting membrane potential
• Autorythmic cells have an unstable membrane potential that continuously
depolarizes, drifting slowly towards threshold
• These spontaneous changing membrane potentials (pacemaker potentials) initiate
action potentials that spread and trigger contractions
◦ Action potentials of pacemaker cells
▪ Pacemaker potential
▪ Depolarization
▪ Repolarization
◦ Sequence of excitation
◦ SA node generates impulses
◦ Impulse pause at AV node
◦ AV bundle connects atria to ventricles
◦ Bundle branches conduct the impulses through the interventricular septum
◦ The subendocardial conducting network depolarizes the contractile cells of both
ventricles
◦ Excitation- Contraction Coupling
1. Ca2+ induced Ca2+ release upon depolarization
Ca2+ that entered through sarcolemma triggers opening of Ca2+ channels in sarcoplasmic reticulum,
leads to more Ca2+ in cytosol
2. Ca2+ binds to troponin, revealing myosin binding sites of actin
3. Repolarization- cytosolic Ca2+ decreases
Active transport of Ca2+ back to SR
Also exit to extraculluar fluid via Na+-Ca2+ channels
Electrocardiogram
• 3 waves
◦ P wave- results from movement of depolarization wave from SA node through to atria
(Approx 0.08s in length)
▪ Approx 0.1s after P wave begins, atria contract
◦ QRS complex- results from ventricular depolarization and precedes ventricular contraction
(Approx 0.08s in length)
◦ T wave- results from ventricular re polarization (Approx 0.16s)
Cardiac Cycle
• Heart Sounds
◦ Basic rhythm- lub-dub, pauses, lub-dub
▪ Pause indicates period of relaxation
▪ First sound (lub) occurs as AV valves close
▪ Second sound (dub) occurs as SL valves close
◦ Two other weak sounds are audible
◦ Heart murmurs- obstruction causes blood flow to become turbulent and generates abnormal
heart sounds
▪ Incompetent valve- fails to close properly
▪ Stenotic valve- fails to open properly
• Cardiac Cycle- includes all events associated with blood flow through heart during one
complete heart beat
◦ Ventricular filling- mid to late diastole- blood returning from circulation is flowing
passively through atria and open AV valves into ventricles, following depolarization atria
contract, compressing blood into chambers, blood is propelled into ventricles, atria relax,
ventricles depolarize
◦ Ventricular systole (atria is diastole)- As atria relax, ventricles begin contracting, walls close
in on blood in their chambers, AV valves close, isovolumetric contraction phase, then SL
valves are forced open and blood rushes from ventricles into aorta and pulmonary trunk
◦ Isovolumetric relaxation- early diastole- ventricles relax, blood remaining in their chambers
(end systolic volume) is no longer compressed , blood in aorta and pulmonary trunk flows
backward, toward heart, closing SL valves and once again ventricles are completely closed
◦ At a normal heart rate of 75bmp, cardiac cycle lasts 0.8s
Cardiac Output
CO = HR x SV
• Cardiac reserve- difference between resting and maximal CO
• SV represent the difference between EDV and ESV
• Regulation of SV
◦ Preload- degree of stretch of heart muscle before contraction (high preload- high SV)
▪ Frank- starling law of heart- greater EDV gives optimal sarcomere length which gives
better stretch and therefor better contractiblity
◦ Contractility- contractile strength achieved at a given muscle length
◦ Afterload- back pressure exerted by arterial blood (pressure ventricles must overcome to
eject blood)
• Regulation of HR
◦ Autonomic regulation- when emotional or physical stressors act, sympathetic nerve fibres
release norepinephrine which binds to receptors, causing threshold to be reached quicker
◦ Chemical regulation- hormones (epinephrine and thyroxine) and ions (potassium and
calcium)
◦ Other factors include age, gender, exercise and temp
Activation of the sympathetic nervous system increases HR and contractility
Activation of the parasympathetic nervous system decreases HR but has little effect on contractility
Homeostatic Imbalance
• Congestive heart failure- pump is inadequate and can not meet circulation needs
• Coronary atherosclerosis- fatty build up that clogs coronary arteries
• Persistent high blood pressure- myocardium must exert more force to open AV valve eventually
causing myocardium to weaken
• Multiple MI- depresses pumping efficiency as scar tissue replaces dead heart cells
• Dilated cardiomyopathy- ventricles stretch and become flabby, myocardium deteriorates
Developmental Aspects
• The heart begins as a mesodermal tube
• By day 20 the endothelial tubes begin to fuse
• By day 22 the heart starts pumping blood
• By day 24 the heart continues to elongate and bend
• By day 28 the bending continues
• The fetal heart has 2 lung bypasses (foramen ovale and ductus arteriosus)
• Congenital heart defects
◦ Ventricular septal defect- superior part of interventricular septum fails to form (1/500 births)
◦ Coarctation of aorta- part of aorta is narrowed, increasing work load of left ventricle
(1/1500 births)
Physiology of Circulation
• Sources of resistance
◦ Blood viscosity
◦ Total blood vessel length (longer vessel = greater resistance)
◦ Blood vessel diameter
• Blood pressure
◦ Arterial blood pressure reflects how much elastic arteries can stretch and the volume of
blood forced into them
◦ Pulse pressure- the difference between systolic and diastolic pressure
◦ Mean arterial pressure- pressure that propels blood to the tissues
▪ Considers the fact that heart does not spend same amount of time in systole and diastole
▪ MAP= diastolic pressure + pulse pressure/ 3
◦ Capillary blood pressure is significantly lower because of fragility of capillaries
◦ Venous return (3 mechanisms)
▪ Muscular pump
▪ Respiratory pump
▪ Sympathetic venoconstriction
• Short term regulation of blood pressure
◦ Neural controls
▪ 2 main goals
1. Maintain adequate MAP by altering blood vessel diameter
2. Altering blood distribution to respond to specific demands of various organs
• Vasomotor centre- controls diameter of blood vessels, transmits impulse down
vasomotor fibers
◦ Blood pressure is modified by:
▪ Baroreceptor reflexes
• Baroreceptors- stretch receptors, when stretched they send an inhibitory
impulse that decreases blood pressure
◦ 3 mechanisms
▪ Arteriolar vasodilation- decreased output from vasomotor centre
allows arterioles to dilate, peripheral resistance and MAP fall
▪ Venodilation- decreased output from vasomotor center allows veins to
dilate, decreases venous return and CO
▪ Decreased cardiac output- as CO falls, so does MAP
▪ Chemoreceptors
• Transmit impulse to cardioaccelery center which activates reflexes
(regarding O2)
Lymphoid cells
1. Lymphocytes- arise in bone marrow and mature into T lymphocytes (immune responses) and B
lymphocytes (production on plasma cells which release antibodies)
2. Macrophages
3. Dendritic cells- capture antigens and return them to lymph nodes
4. Reticular cells- produce reticular fiber- stroma which is the support network
Lymphoid tissue
• Roles
1. Houses and provides proliferation site for lymphocytes
2. Furnishes an ideal surveillance point for lymphocytes and macrophages
• Largely composed of reticular connective tissue
• Diffuse lymphoid tissue- loose arrangement of lymphoid cells
• Lymphoid follicle (nodules)- solid, spherical bodies consisting of tightly packed cells
Lymph nodes
• Functions
1. Filtration of lymph
2. Immune system activation (site of immune response)
Lymphoid Organs
1. Primary Lymphoid Organs
• Lymphocyte development
• Fetal liver, bone marrow and thymus
2. Secondary Lymphoid Organs
• Lymphocyte activation
• Lymph nodes, spleen, and mucosa associated lymphoid tissue (Tonsils, appendix, Peyer's
Patches)
Immune System
• Two intrinsic dense systems:
1.Innate Defences
• Surface barriers- skin and mucosa, produce various substances including acid, enzymes, mucin,
defensins (antimicrobial peptides) and other chemicals
• Internal defences- phagocytes (neutrophils and macrophages), natural killer cells (kill cancer
cells and virus infected cells before adaptive defence is activated by detecting general
abnormalities, induce apoptosis) inflammation, antimicrobial proteins
◦ Antimicrobial proteins
▪ Interferons- secreted by infected cells in an effort to save adjacent cells
▪ Compliment proteins- plasma proteins that compliment immune response
◦ Opsonization- process of coating a pathogen in opsonins (complement proteins or
antibodies that provide handles for phagocyte receptors to bind)
◦ Roles of inflammation- prevents spread of damaging agents, disposes of cell debris and
pathogens, alerts adaptive immune system, sets stage for repair
2.Adaptive Defences
• “Third line of defence”
• Attacks particular foreign substances
• 4 properties
◦ Specificity
◦ Diversity
◦ Memory
◦ Tolerance
• Humoral immunity (B cells) and cellular immunity (T cells)
◦ Humoral immunity
▪ A naive B cell is exposed to an antigen, the cell is activated and cell division occurs, one
of these daughter cells becomes a memory cell, the other divides and produced
antibodies that cirulate and destroy the corresponding antigen by clumping (indirect
attack)
◦ Cellular immunity
▪ Naive T cell recognizes abnormalities that have been presented in fragments on infected
cells surface, T cells bind and are activated, T cells divide similarly to the B cell but
destroy the infected cell by poking holes in it and injecting enzymes (direct attack)
• Helper T cells are required for full activation of most B and T cells.
Antibodies
• Antibody monomer- 4 polypeptide chains, each has a constant region which determines the
antibodies function and class and a variable region which enables the antibody to recognize its
specific antigen
• Five classes
◦ IgM
◦ IgA
◦ IgD
◦ IgG
◦ IgE
• Antibody functions
◦ Complement fixation
◦ Antigen neutralization
◦ Precipitation
◦ Agglutination
Homeostatic imbalance
• Immunodeficiency- includes AIDs caused by HIV and SCID syndromes, overwhelming
infections are fatal
• Autoimmune diseases- occurs when body regards its own tissues as foreign and mounts an
immune attack against them. Ex rheumatoid arthritis and multiple sclerosis
• Hypersensitivities- abnormally intense reaction to an otherwise harmless antigen
Components
• 2 zones
◦ Respiratory zone- site of gas exchange (bronchioles, alveolar ducts, alveolar)
◦ Conducting zone- all other resp passages, provide passage and cleanse, humidify and warm
air
• Respiratory membrane
◦ Walls of alveoli are single layer of squamous epithelium cells (type 1 alveolar cells)
surrounded by a thin membrane
◦ External surface of alveoli are densely covered with cobweb of capillaries forming
respiratory membrane with other structures
▪ Gas exchange occurs by simple diffusion through respiratory membrane
◦ Type 2 alveolor cells (cubodial epithelium) are scattered amid type 1 cells and secrete
surfactant and antimicrobial proteins
• Lungs
◦ Terminal bronchioles feed into respiratory bronchioles
◦ Left lung divided into superior and inferior lobes, separated by oblique fissure
◦ Right lung divided into superior, middle and inferior lobes by oblique and horizontal
fissures
◦ Lobules- smallest division of lung visible with naked eye
◦ Blood supply and innervation
▪ Pulmonary circulation- pulmonary arteries deliver systemic venous blood, pulmonary
arteries branch and feed into pulmonary capillary network, pulmonary veins convey
blood to heart
• Low pressure, high volume
▪ Bronchial circulation- bronchial arteries provide oxygenated systemic blood to lung
tissue
• High pressure, low volume, circulation to everything but alveolar
▪ Innervation- parasympathetic and sympathetic motor fibres and visceral sensory fivers
all enter lung through pulmonary plexus
• Parasympathetic fibres- cause constriction
• Sympathetic fibres- cause dilation
◦ Pleurae- form thin serosa, produces pleural fluid which fills pleural cavity allowing for
gliding of lungs during breathing
Breathing
• Pressure relationships
◦ Described relative to atmospheric pressure which is pressure exerted by air surrounding the
body
▪ Negative pressure indicated pressure lower than atmospheric pressure by a certain
amount
◦ Intrapulmonary pressure- pressure in alveoli
▪ Rises as falls with phases of breathing but always eqaulizes with atmospheric pressure
eventually
◦ Intraplueral pressure- pressure in pleural cavity
▪ Fluctuates with breathing, always about 4mmHg less than intrapulmonary pressure
• Pulmonary ventilation
◦ Volume changes lead to pressure changes, leading to the flow of gases to equalize pressure
▪ Boyles law
• P1V1 = P2V2
• Inspiration
◦ Diaphragm contraction causes height of thoracic cavity to increase
◦ Intercostal muscles- contraction lifts rib cage and pulls sternum superiorly, expanding
diameter or thorax
▪ These actions expand the thoracic dimensions by nearly 500ml
▪ As thoracic dimensions increase, lungs stretch, intrapulmonary volume increases,
intrapulmonary pressure drops 1mmHg, air rushes into lungs along pressure gradient
▪ Inspiration ends when intrapulmonary pressure = atmospheric pressure, intrapleural
pressure declines 6mmHg
• Expiration
◦ Passive, dependant on lung elasticity
◦ As inspiratory muscles relax, thoracic and intrapulmonary volumes decrease, compressing
alveolar
◦ Intrapulmonary pressure rises 1mmHg, when intrapulomary pressure in greater than
atmospheric pressure, pressure gradient forces air out of lungs
• Lung properties
1. Compliance- lungs can stretch
2. Elasticity- lungs can recoil after stretch
• Respiratory Volumes
◦ Tidal volume (TV)- amount of air that moves in and out with each breath
◦ Inspiratory reserve volume (IRV)- amount of air that can inspired forcibly beyond TV
◦ Expiratory reserve volume (ERV)- amount of air that can expelled from lungs after a normal
tidal volume expiration
◦ Residual volume (RV)- air remaining in lungs
• Respiratory Capacities
◦ Inspiratory capacity (IC)- total amount of air that can be inspired after normal TV expiration
(sum of TV and IRV)
◦ Functional residual capacity (FRC)- amount of air remaining in lungs after normal TV
expiration (sum of RV and ERV)
◦ Vital capacity (VC)- total amount of exchangeable air (sum of TV, IRV, ERV)
◦ Total lung capacity (TLC)- sum of all lung volumes
• Pulmonary function tests (spirometry)
◦ Forced vital capacity (FVC)- amount of gas expelled when a subject takes a deep breath and
forcefully exhales maximally and rapidly
◦ Forced expiratory volume (FEV)- amount of air expelled during specific time intervals of
FVC test
• Anatomical dead space is the air-filled volume (about 150ml) of the conducting passageways. If
alveoli become nonfunctional their volume is added to dead space
• Alveolar ventilation is the best index of ventilation efficiency because it accounts for
anatomical dead space
◦ AVR= (TV- dead space) x respiratory rate
◦ Internal respiration- gas exchange that occurs between the systemic capillaries and the
tissues
▪ CO2 enters the blood, O2 leaves the blood and enters the tissues
• Dalton's law of partial pressures- total pressure exerted by a mixture of gases is the sum of the
pressures exerted independently by each gas in the mixture
• Henry's law- when a gas is in contract with a liquid, the gas will dissolve in the liquid in
proportion to its partial pressure
◦ Blood O2 and Henry's Law
▪ For a liquid and gas at equilibrium, the amount of gas dissolved depends on solubility of
gas in fluid and partial pressure of gas (changes will altitude)
• O2 Transport
◦ Cooperative binding- once one O2 binds, the others bind more easily, unloading of one also
facilitates the unloading of others
◦ Rate of Hb binding and release of O2 is regulated by various factors including:
▪ PO2
▪ Temperature (higher temp= lower affinity for O2)
▪ Blood pH (increased Co2= more acidic= lower affinity for O2)
▪ PCO2
◦ Bohr effect: tense configuration (low O2 affinity)
▪ Stabalized by deceased pH, increased PCO2 in blood and increased temperature
◦ Hb has a higher affinity for O2 in lungs, lower affinity in tissues (related to Bohr effect,
allows for drop off of O2 in tissues)
◦ % saturation = (# of O2 molecules bound) / (# of binding sites) x100
◦ 2,3-biophosphoglyceric acid (2,3-BPG)
▪ Biproduct of anaerobic respiration
▪ Bonds with deoxyhaemoglobin and stabilizes it
• Favours O2 unloading (lowers affinity for O2)
• CO2 Transport
◦ 3 forms
▪ Dissolved in plasma (small amount)
▪ Chemically bound to haemoglobin (carbaminohaemoglobin)
▪ Bicarbonate ions in plasma
◦ Haldane effect- reflects greater ability of reduced hemoglobin to form
carbaminohaemoglobin and buffer H+ by combining with it (dissociation of O2 allows more
CO2 to combine with Hb)
Control of Respiration
• Neural mechanisms
◦ Medullary respiratory centres are the ventral and dorsal respiratory groups
▪ Ventral group likely responsible for rhythmicity of breathing
◦ Pontine respiratory centres influence the activity of the medullary respiratory centres
Breathing Rate and Depth
• Rising CO2 levels cause reflexive increase in breathing rate and depth, low CO2 levels depress
respiration
• O2 levels affect breathing only indirectly by influencing peripheral chemoreceptor sensitivity to
change in CO2 levels
• Arterial O2 levels below 60mmHg is a major stimulus for respiration
• Changes in arterial pH act indirectly through peripheral chemoreceptors to alter ventilation
• Response to hypoventilation
◦ Hypoventilation leads to hypercapnia (high CO2) which leads to acidosis
◦ The response is hyperventilation which leads to hyopcapnia leading to alkalosis
◦ Response is then to lower breathing, cycling through until normal levels are achieved
• Response to exercise
◦ Exercise leads to hyperpnea (not hyperventilation) (arterial PO2 , PCO2 and pH remain
fairly constant)
• Response to altitude
◦ PO2 decreases with altitude, causing hyperventilation initially, PCO2 drops and alkalosis
occurs, affinity for O2 increases
◦ Over time -2,3-DPG increases, this decreases the affinity for O2 and there is more
unloading of O2 in the tissues
◦ In a long term scenario kidneys increase their erythropoitin production, RBC count
increases and there is more O2 carried in the blood
1. Motility
2. Secretion
3. Digestion
4. Absorption
5. Storage
6. Elimination
Digestive Processes
1. Ingestion
2. Propulsion
3. Mechanical breakdown
4. Digestion
5. Absorption
6. Delectation
Components
• 2 main groups of organs
◦ Alimentary canal- GI tract
▪ Digests, breaks down and absorbs
▪ Mouth, pharynx, esophagus, stomach, intestines
▪ Layers of alimentary canal
• Mucosa- secretes, absorbs and protects
◦ Simple columnar (stratified squamous in mouth,esophagus and anus)
• Submucosa- contains lymph vessels and never fibres
◦ Areolar connective tissue, abundant elastic fibers
• Muscularis externa- responsible for segmentation and peristalsis
◦ Inner circular layer, outer longitudinal layer
◦ Often form spincters
• Serosa- outer most layer
◦ Areolar connective tissue covered in mesothelium
◦ Accessory digestive organs
▪ Teeth, tongue, gallbladder, digestive glands, salivary glands, liver, pancreas
▪ Produce secretions that help breakdown food
• Functional anatomy
◦ Mouth- digestion starts here, saliva contains amylase and antimicrobial agents, lubricate
mouth and dissolves chemicals, stimulates taste buds
◦ Salivary glands
▪ Extrinsic (major) salivary glands- outside oral cavity
▪ Intrinsic (minor) salivary glands- throughout oral cavity
▪ Saliva- mainly water, contains antibodies, enzymes and defensins
▪ Salivation- controlled by parasympathetic NS by salivary nuclei in brain stem
◦ Esophagus
▪ Skeletal muscle for upper, smooth muscle for lower
▪ Swallowing
• Buccal phase (upper esophageal sphincter contracts, tongue presses against hard
palate
• Pharyngeal esophageal phase (uvula and larynx rise, tongue blocks off mouth,
esophageal spincter relaxes, food enters)
• Constrictor muscles of pharynx contract
• Paristalsis
• Gastrointensinal sphincter opens (food enters stomach)
◦ Stomach
▪ Regions
• Cardia- surrounds cardial orifice, where food enters, has mucous glands which
secretes protective secretions
• Fundus- dome-shaped area
• Body- mix of food and stomach secretions
• Pyloris- allows food to pass to intestines, funnel-shaped, narrows to pyloric canal,
terminating at pylorus
• Lining of stomach- simple columnar epithelium, mucus cells
◦ Contains gastric pits and glands
▪ Cells and Secretions
• Mucous neck cells- muscous
• Parietal cells- HCL
• Chief cells- pepsinogen
• Enteroendocrine cells (G cells [gastrin] and ECL cells [histamine, seratonin])
▪ Mucosal barrier- createe from thick coating of bi-carbonate rich mucous on stomach
wall, joined by tight junctions that prevent leaking of gastric juices, damaged cells are
shed and quickly replaced
▪ Essential function of the stomach- intrinsic factor (polypeptide needed for vitamin B12
absorption in intestine)
▪ Digestive processes in stomach
• Gastric secretion
◦ Cephalic (reflex) phase- before food enters stomach
◦ Gastric phase- 3-4hrs
▪ Stimuli- distension, peptides and low acidity
▪ ACH release increases gastric juice output
▪ Neural influences- gastrin
◦ Intestinal phase
• Gastric motility
◦ Propulsion
◦ Grinding
◦ Retropulsion
• Stomach filing
◦ Receptive relaxation of smooth muscle and stomach fundus with food moving
through esophagus into stomach
◦ Gastric accomodation- smooth muscle plasticity, stretch without increasing
tension
• Gastric contractile activity
◦ Peristalsis begins at gastroesophageal sphincter, rippling movement, stronger as
they reach plyoris
• Gastric emptying
◦ 4hrs after meal
◦ Liquids pass straight through
◦ Dependant on duodenum contents
◦ Small Intestine
▪ Duodenum
▪ Jejunum
▪ Ilieum
▪ Intestinal juice- largely water, contains some mucus, enzyme poor
• Stimulation- hypertonic or acid chyme
◦ Pancreas
▪ Posterior to stomach, endocrine function by pancreatic islets (release insulin and
glucagon)
▪ Pancreatic juice- enzymes for food breakdown, includes bicarbonate solution and
digestive enzymes
◦ Liver
▪ Metabolic and hematological regulation, blood detox, carbohydrate metabolism, lipid
metabolism, vitamin storage (A,D,E,K,B12), iron storage (as ferritin), synthesis os
plasma proteins, bile production and secretion
▪ 4 lobes, tissue arranged in lobules, central vein in the middle
▪ Liver blood flow- hepatic portal system
• Digestion products absorbed into intestinal blood capillaries delivered to liver before
general circulation
◦ Extra capillary network- Intestinal capillaries-> hepatic portal vein -> hepatic
capillaries-> hepatic vein
▪ Liver gets venous blood from intestine, arterial blood from hepatic artery
▪ Bile- bilirubin, bile salts, phospholipids, cholesterol, inorganic ions
• Enterohepatic cirulation- recirculated between liver and intestine
• Gallbladder- stores, concentrates bile, sphincter of Oddi in common bile duct
▪ Large intestine- absorption of water, electrolytes, B, K vitamins and folic acid, no
digestion
• Columnar epithelium, goblet cells, no villi, bacterial flora
◦ Defecation
▪ 12-24hrs to reduce meal residue to feces
• Feces 75% water, 24% solids (bacterial, fibre, small amounts of protein,
sloughed epithelial cells, salts, mucous)
▪ Rectal pressure rises as feces accumulates
▪ Longitudinal rectal muscles contract to increase rectal pressure
• Stretch stimulates defecation reflex
◦ Intrinsic defecation reflex
◦ Parasympathetic defecation reflex
Digestion and Absorption
• Digestion of carbs
◦ Salivary amylase- digests starch
◦ Pancreatic amylase- digests other starch in small intestine
◦ Dextrinase and glucoamylase- act on oligosccharides composed of more than 3 simple
sugars
• Digestion of protein
◦ Pepsinogen- activaed to pepsin- breaks down proteins
◦ Trypsin and chymotrypsin- cleave proteins into smaller peptides
◦ Carbooxypeptidase- splits off one amino acid at a time
◦ Aminopeptidase and dipeptidase- breakdown final amino acid products
• Digestion of fat
◦ Lipases- fat digesting enzymes
◦ Bile salts form emulsions with fat, increasing surface area exposed to enzymes
• Digestion of nucleic acids
Week 7- Metabolism
Metabolic Reactions
Metabolic Pathways
• Many steps
• Starts with specific molecules
• Finish with products
• Catalysed by enzymes
Metabolism
• Sum of all chemical reactions in the body
Anabolism and Catabolism
• Anabolism- the general term for all reactions that build larger molecules or structures from
smaller ones
◦ Uses energy
• Catabolism- all process that break down complex structures to simpler ones
◦ Release of energy
◦ Cellular respiration- foods are broken down in cells and some of the energy released is
captured to form ATP
▪ ATP then serves to links energy releasing catabolic reactions to cellular work
• Energy from catabolism drives anabolism
Catabolic Pathways
• Oxidize organic fuels produced by plants
• Yield ATP
◦ ATP provides energy for cellular work
◦ Involves transfer of electrons
• Fermentation
◦ Partial breakdown of sugars
◦ Without O2
• Cellular respiration
◦ Uses O2 and organic molecules to yield ATP
Phosphorylation
• Note: Reactions driven by ATP are coupled, enzymes shift its high energy phosphate groups to
other molecules which then said to be phosphorylated
• Phosphorylation primes a molecule to change in a way that increases its activity, produces
motion or does work
◦ Substrate level phosphorylation- occurs when high energy phosphate group is transferred
directly from a substrate to ADP to form ATP. This reaction occurs in both the cytosol and
mitochondrial matrix
▪ ATP formed directly during glycolysis and citric acid cycle
◦ Oxidative phosphorlyation- occurs in the mitochondria, carried out by electron transport
proteins that act as proton pumps to create a protein gradient across the inner mitochondrial
1)Carbohydrates
• Glucose breakdown
1. Gylcolysis
Converts glucose to pyruvate
2. Krebs cycle (TCA Cycle or citric acid cycle)
Oxidized pyruvate to CO2
3. Electron transport chain and oxidative phosphorylation
Coverts chemical energy to make ATP
Electron Transport Chain and Oxidative Phosphorylation- carries out final catabolic reactions that
occur on mitochondrial cristae
• Oxidative phosphorylation
2)Lipids
• Triglycerides are energy source lipids
• Lipogenesis- triglyceride synthesis
• End products of lipid digestion and cholesterol are transported in blood in the form of
chylomicrons
• Glyercol is converted to gylceraldehyde 3-phosphate and enters the Krebs cycle or is converted
to glucose
• Fatty acids are oxidized by beta oxidation into acetic acid fragments. These are bound to
coenzyme A and enter the Krebs cycle as acetyl CoA. Dietary fats not needed for energy or
structural materials are stored in adipose tissue.
• There is a continual turnover of fats in fat deposits.
• Lipolysis- breakdwon of fats to fatty acids
• When excessive amounts of fats are used the liver converts acetyl CoA to ketone bodies and
releases them into the blood. Excessive levels of ketone bodies (ketosis) can lead to metabolic
acidosis
• All cells use phospholipids and cholesterol to build their plasma membranes. The liver forms
many functional molecules from lipids
• Triglyceride structure- glycerol and 3 fatty acids
• Proteins
• To be oxidized for energy, amino acids are converted to keto acids that can enter the Krebs
cycle. This involves transamination, oxidative deamination and keto acid modification
• Amine groups removed during deamination (as ammonia) are combined with CO2 by the liver
to from urea which is excreted in urine
• Deaminated amino acids may also be converted to fatty acids and glucose
• Amino acids are the body's most important building blocks. Nonessential amino acids are made
in the liver by transamination
• In adults, most protein synthesis serves to replace tissue proteins and maintain nitrogen balance
• Protein synthesis requires the presence of all 10 essential amino acids. If any are lacking, amino
acids are used as energy fuels.
Kidney Functions
• Regulating the total volume of water in the body and the total concentration of solutes in that
water (osmoality)
• Regulating the concentrations of various ions in the extracellular fluid
• Ensuring long-term acid base balance
• Excreting metabolic wastes and foreign substances
• Producing erythropoietin and renin
• Converting vit D to active form
• Carrying out gluconeogensis during prolonged fasting
Urinary system also includes
• Ureters- tubes that transport urine from kidneys to urinary bladder
• Urinary bladder-temporary storage reservoir
• Urethra- tube that carries urine from bladder to body exterior
Kidney Anatomy
• Three layers of supportive tissue
◦ Renal fascia- outer layer of dense fibrous connective tissue that anchors kidney and adrenal
gland to surrounding structures
◦ Perirenal fat capsule- a fatty mass that surrounds the kidney and cushions it against blows
◦ Fibrous capsule- a transparent capsule that prevents infections from surrounding regions
Renal ptosis- when one or both kidneys drop to a lower position because of change to fat capsule, may
lead to urinary backup which can lead to water in the kidney (hydronephrosis) which can lead to tissue
damage
Nephrons
• Structural and functional units of the kidneys
• Carry out processes that form urine
• Collecting ducts collect fluid from several nephrons and convey it to renal pelvis
• Renal corpuscle- consists of a tuft of capillaries called glomerulus and a glomerular capsule
◦ Glmoerulus- fenstrated, large amounts of solute rich but protein free fluid passes from blood
into glomerular capsule
◦ Glomerular capsule
▪ Parietal layer- structural functions only
▪ Visceral layer- podocytes terminate into foot processes which interdigitate as they cling
to the basement membrane. Filtration slits at food processes that allows filtrate to enter
capsular space
Classes of Nephrons
• Cortical nephrons- most abundant, located almost entirely in cortex
• Juxtamedullary nephrons- originate near cortex medulla junction, play important role in kidneys
ability to produce concentrated urine, long nephron loops that deeply invade the medulla
◦ Granular cells- act as mechanoreceptirs that sense blood pressure in afferent arteriole
◦ Extraglomerular mesangial cells- pass regulatory signals between macula densa and
granular cells
Micturition
• Urination/ voiding
• For this to occur, 3 things occur simultaneously
◦ Detrusor must contract
◦ Internal urethral sphincter must open
◦ External urethral sphincter must open
• Accumulating urine stretches bladder wall which initiates the micturition reflex
Fluid Compartments
• Intracellular fluid compartment
◦ Consists of trillions of tiny compartments (cells)
• Extracellular fluid compartments
Influence of ADH
• ADH levels low- most water reaching ducts is not reabsorbed resulting in dilute urine and
reduced volume of body fluids
• ADH levels high- aquaporins inserted in principal cell apical membrane and nearly all filtered
water is reabsorbed, small volume of concentrated urine is excreted
Electrolyte Balance
• Role of Sodium- exert bulk of ECF osmotic pressure and control water volume and distribution
in body
• Regulation of sodium balance
◦ linked to ECF volume and blood pressure regulation, involves neural and hormonal controls
◦ Aldosterone promotes sodium reabsorption to maintain blood volume and pressure
◦ Declining blood pressure and falling filtrate NaCl concentration stimulate granular cells to
release renin which enhances systemic blood pressure, Na+ reabsorbtion and water
excretion
◦ Atrial natruretic peptide causes systemic vasodilation and inhibits renin, aldosterone and
ADH release
◦ Estrogens and glucocorticoids increase retention of sodium, progesterone promotes sodium
and water excretion
◦ Cardiovascular system senses changing blood pressure and prompts changes in sympathetic
vasomotor activity
Regulation of Phosphate
• Needed for bone minerization
• Reabsorbed in PCT (stimulated by calcitriol, inhibited by PTH)
• Fecal loss (but intestinal absorption supported by calcitriol and PTH)
Chloride Regulation
• Most abundant anion in ECF
• Absorbed across digestive tract with Na+
• Follows Na in PCT
• Less Cl- absorbed during acidosis (HCO3- favoured)
• Minimal loss in sweat and urine
Buffers
• Stabalize pH by providing or removing H+
Homeostatic Imbalances
▪ Lined with ciliated columnar epithelium which secretes fluid to support sperm
▪ Smooth muscle wall moves sperm along
◦ Vas deferens
▪ Continues from epididymis
▪ Passes through inguinal canal in abdomen
▪ Reaches posterior side of bladder
▪ Lined with partially ciliated columnar epithelium
▪ Ampulla- expanded portion
▪ Joins with duct of seminal vesicle and together for ejaculatory duct which passes
through the prostate gland to join the urethra
◦ Seminal vesicles
▪ Posterior side of bladder
▪ Coiled membranous pouches
▪ Lining secretes fluid into ejaculatory duct
• Alkaline (pH modifies pH of sperm)
• Fructose (provides energy for sperm)
• Prostoglandins (promotes muscular contractions of female genital tract)
◦ Urethra
▪ Conveys both urine and semen
▪ 3 regions
• Prostatic urethra- portion surrounded by prostate
• Intermediate part of urethra- membranous urethra, in urogenital diaphragm
• Spongy urethra- runs through penis and opens to outside of external urethral orifice
• Accessory Organs
◦ Prostate
▪ Encircles urethra, inferior to bladder
▪ Has capsule with fibrous connective tissue that divides gland into lobes each with 40-50
tubules
▪ Secretes fluid into urethra
• Thin, milky, alkaline
• Adjusts sperm pH
• Enhances sperm motility
◦ Bulbo-Urethral Glands
▪ Inferior to prostate
▪ Enclosed by fibers if urethral sphincter
▪ Tubules secrete fluid into urethra
• Mucus like, lubricates the penis
• Semen
◦ Sperm is 2% of semen
◦ Remaining
▪ Fluids from seminal vesicles (60%)
▪ Fluids from prostate gland (35%)
▪ Fluids from bulbourethral glands (3%)
◦ Typical ejaculation is 2-5mL, approx 20-100 million spermatozoa per mL
◦ pH 7.2-8.0
◦ Contains prostaglandins, relaxin, ATP, ingredient to suppress female immune response,
antibiotic chemicals, clotting factors
• Physiology of Male Resproductive System
◦ Erection
▪ Sexual excitment tirggers a parasympathetic reflex that promotes release of nitric oxide
locally which relaxes smooth muscle in penile blood vessel walls, dilating arterioles and
allowing erectile bodies to fill with blood
▪ Expansion of corpora cavernosa compresses drainage veins in order to retard blood
outflow
▪ Corpus spongiosum expands slightly, main function is to keep urethra open during
▪ CNS responds to sexual stimuli by activating parasympathetic neurons that innervate
internal pudendal arteries ejaculation
◦ Ejaculation
▪ Under sympathetic control
▪ When impulses provoking erection reach critical level a spinal reflex is initiated and
discharge of nerve impulses occurs over sympathetic nerves
▪ Bladder sphincter constricts preventing expulsion of urine or reflux of semen into
bladder
▪ Reproductive duct and accessory glands contract, emptying contents into urethra
▪ Semen in urethra triggers a spinal reflex through somatic motor neurons, semen is
propeeled from urethra
▪ Activity of sympathetic never fibres constricts the internal pudendal arteries, reducing
blood flow to penis and forces blood out
• Spermatogenesis
◦ Sequence of events in seminiferous tubules of testes that produces male gametes
◦ Healthly adult produces 400 million sperm per day
◦ Diploid chromosomal number- normal chromosome number in most body cells, symbolized
as 2n, in human 46
◦ Haploid chromosomal number- number of chromosome in gametes, symbolized as n, in
humans 23
◦ Mitosis- type of division that occurs with most body cells, distributes replicated
chromosomes equally between daughter cells so that each daughter cells receives a full set
of chromosomes identical to the mother cell
◦ Meiosis- type of nuclear division that occurs in gonads, consists of 2 consecutive nuclear
division that follow one round of DNA replication, product is 4 daughter cells instead of 2,
each with half as many chromosomes as diploid body cells (reduces 2n to n) introduces
genetic variation because each of the haploid daughter cells only has some of the genes of
each parent
▪ 2 nuclear divisions, each consisting of 4 phases
• Meiosis 1- reduction division of meiosis
◦ Reduces chromosome number from 2n to n
◦ Similar to mitsosis expect in prophase 1 the replicated chromosomes seek out
their homologous partners and pair up with them (synapsis) forms tertad.
Crossovers (chiasmata) then occurs where one end of one maternal and one
paternal chromatid wrap around each other within the tetrad.
◦ During metaphase tetrads line up randomly and during anaphase the sister
chromotids and homologous chromosomes are distributed to opposite end of the
cell
◦ Results in two copies of one member of each homologous pair and none of the
other in each daughter cell and a haploid chromosomal number but twice the
amount of DNA
• Meiosis 2- equal division of meiosis
◦ Mirror mitosis in every way except that chromosomes are not replicated before it
begins, instead sister chromatids are parcelled out among four cells
◦ Reduces chromosomal number by half
◦ Introduced genetic variability
◦ Events in Seminiferous Tubules
▪ Spermatogenic cells- give rise to sperm in a series of division and cellular
transformations
▪ Mitosis of Spermatogonia- forming spermatocytes
• Spermatogonia- outer most tubule cells, divide continuously by mitosis, until
puberty all daughter cells become spermatogonia. After puberty each mitotic
division of a spermatogonium results in type A and type B daughter cells
◦ Type A remain basal lamina
◦ Type B get pushed to lumen and become a primary spermatocyte destined to
produce 4 sperm
▪ Meiosis- Spermatocyte to Spermatids
• Each spermatocyte undergoes meiosis 1, forming two smaller haploid cells
(secondary spermatocytes)
• These continue rapidly to meiosis 2, producing spermatids
• Midway through spermatogenesis the developing sperm turn off all the their and
compact their DNA
▪ Spermatogenesis- Spermatids to sperm
• Sperm must undergo speriogenesis during which is elongates, sheds its excess
cytoplasmic baggage and forms a tail, result is a spermatozoon
• Head of sperm contains DNA, acrosome adheres to the top of the nucleus, midpiece
contains mitochondria spiraled around tail . Long tail is a flagellum
• Sustenocytes- sertoli cells, divide seminiferous tubule into two compartments.
◦ Basal compartment- contains spermatogonia and earliest primary spermatocytes
◦ Adluminal compartment- includes meiitically active cells and tubule lumen
◦ Tight junctions between sustenocytes form the blood testis barrier
• Hormone Regulation
◦ Gonadotropin releasing hormone (GnRH)
▪ From hypothalamus
▪ Stimulates FSH and LH release
◦ Follicle stimulating hormone (FSH)
▪ From anterior pituitary
▪ Stimulates spermatogenesis
◦ Luteinizing hormone (LH)
▪ From anterior pituitary
▪ Stimulates androgen production
◦ Inhibin
▪ From sertoli cells
▪ Blocks FSH secretion
◦ Ovary has an outer cortex which houses forming gametes and inner medulla containing
largest blood vessels and nerves
◦ Ovarian follicles- each consists of an immature egg (oocyte) surrounding cells are follicle
cells if there is a single layer present, granulosa cells when more than one layer is present
◦ Primordial follicles- single layer of follicle
◦ Vesicular follice- fully mature, central fluid filled cavity
• Female Duct System
◦ Fallopian tubes- receive the ovulated oocyte, site of fertilization
▪ At time of ovulation the uterine tube bends to drape over the ovary while the fimbriae
stiffen and sweep the ovarian surface cilia on fimbriae create currents that carry an
oocyte into the uterine tube
▪ Peristalsis and cilia carry oocyte microvilli produce secretions that keep oocyte moist
and nourished
◦ The Uterus
▪ Receives, retains and nourishes a fertilized ovum
▪ Major portion- body, rounded region- fundus, narrowed region- isthmus
▪ Uterine wall
• Perimetrium- incomplete outermost serous layer
• Myometrium- middle layer, contracts during childbirth
• Endometrium- muscosal lining of uterine cavity, embryo implants here, two layers
◦ Stratum functionalis- functional layer undegoes cyclic changes
◦ Stratum basalis- basal layer, deeper, thinner, forms a new functionalis when
menstruation ends
◦ The Vagina
▪ 3 coats
• Outer fibroelastic adventita
• Smooth muscle muscularis
• Inner mucosa
• Vagina has an acidic pH which helps destroy bacteria but is also hostile to sperm
◦ External Genitalia
▪ Mons pubis
▪ Labia majora and labia minora
▪ Clitoris
▪ Greater vestibular glands- release mucous into vestibule and help keep it moist and
lubricated
◦ Mammary glands
• Oogenesis
◦ In fetal period oogonia (diploid stem cells of ovaries) multiply rapidly by mitosis,
primordial follicle appear as oogonia transform into primary oocytes and become
surrounded by follicle cells
◦ Primary oocytes begin first meiotic division but do not complete prophase 1
◦ At birth female has lifetime supply of eggs, by puberty 300, 000 remain
◦ Before puberty all recruited primordial follicle undergo atresia, at puberty FSH rescues a
small number of growing follicles each month
◦ In each cycle one rescued follicle is the dominant follicle and continues meiosis 1,
producing 2 haploid cells, the smaller one is the first polar body and the larger one is the
secondary oocyte
◦ First polar body may continue meiosis 2, secondary oocyte arrest in metaphase 2 and is
ovulated and deteriorates if not fertilized, if fertilization does occur the oocyte completes
Time line
• Gestation period- development occurs
• Fertilzation- 8 weeks- conceptus is called an embryo
• 9 weeks- brith- conceptus is called a fetus
• First trimester- months 1-3 (fertilization, implantation, placenetation, embroyogensis)
growth
◦ Goal- to produce smalls cells with a high surface to volume ratio which enhances their
uptake of nutrients and O2 and disposal of wastes
◦ Provides large number of cells to serve as building blocks
◦ 36 hours after fertilization- first cleavage division of zygote produced 2 identical cells
(blastomeres) which divide to form morula
◦ Transport of embryo to uterus continues
◦ By day 4-5 consists of 100 cells
◦ Blastocyst hatches from inner structure and tropoblast cells begin to display L- selectin
adhesion molecules
◦ They take part in placenta formation and secrete several factors with immunosuppresive
effects
◦ Inner cell mass becomes embryonic disc which forms embryo proper and 3 extraembryonic
membranes
• Implantation
◦ Window of implantation is opened by surging levels of ovarian hormones in blood
◦ If mucosa is properly prepared, integrin and selectin proteins on trophoblast cells bind
respectively to extracelluar matrix and endometrial cells and blastocyst impants high in the
uterus
◦ Endometrium thickens at point of contact and takes on characteristics of an acute
inflammatory responses
◦ Takes about 5 days
◦ Viability of corpus luteum is maintained by LH-like hormone (human chorionic
gonadotropin. HCG)
▪ This is detectable in a pregnancy test
• Placentation
◦ Formation of a placenta
• Early embryonic development
◦ Woman is clinically pregnant
◦ Even while implantation is occurring the blastocyte is being converted to a gastrula in which
the 3 primary germ layers form and extraembryonic membranes develop
▪ Formation of membranes and layers
• Before becoming three-layered, inner cells divided in 2 (epiblast and hypoblast) and
subdivided inner cell mass is embryonic disc
• Extraembryonic membranes that form during the first 2-3 weeks are amnion, yolk
sac, allantois and chorion
• Amnion provides buoyant protective environments and prevents organs from fusing
together during development
• Yolk sac forms digestive tube and is source of earliest blood cells and blood vessels
• Allantois forms at end of yolk sac and functions for waste removal
• Chorion helps form the placenta
▪ Morphogenesis- shaping of embryo
▪ Gastrilation- during week 3 2 layers transform into ectoderm, mesoderm and endoderm
▪ Organogensis- formation of body organs and organ systems (differentiation, starts with
nervous system)
◦ Development of fetal circulation
▪ First blood cells arise is yolk sac
▪ By end of week 3 embryo has a system of paired blood vessels and two vessels forming
the heart have fused and bent into an S shape
Paturation
• Rise in estrogen in last stages of pregnancy, 3 important implications
◦ Stimulates myometrial cells of uterus to form abundant oxytocin receptors
◦ Promotes formation of gap junctions between the uterine smooth muscle cells
◦ Antagonizes progesterone’s quieting influence on uterine muscle
• Braxton Hicks contractions- false contractions caused by relaxation of uterus muscles
• Fetal cells begin to produce oxytocin which causes placenta to release prostalglandins which
stimulate synthesis of more gap junctions in uterine smooth muscle, both are strong muscle
strimulants and contractions become more frequent and vigorous
• Increasing cervical distension activate hypothalamus which signals for oxytocin release by
posterior pituitary
• Several postive feedback mechanisms involving prostaglandins and oxytocin are propelled into
action
• Fetal fibronectin changes to lubricant just before true labor beings
• Antiprostalgandins (ibuprofen) can inhibit early stages of labor
• Stages of labor
◦ Dilation
▪ Time from labors onset until cervix is fully dialted (10cm)
▪ Weak but regular contractions begin
▪ At first 15-30 min apart and in superior uterine muscles, last for 10-30 seconds
▪ Lower uterus gets involved and contractions are faster and more vigorous
▪ Eventually amnion ruptures
▪ Last 6-12 hours of more
▪ Engagements occurs when infants head enters the true pelvis
▪ Descent continues and babies head rotates so that its greatest dimension is in the
anteroposterior line
◦ Expulsion
▪ From dilation to delivery
▪ Strong contractions every 2-3 minutes, lasting 1 minute
▪ May last up to 2 hrs, usually 50 min, 20 minutes in subsequent births
▪ Crowning when largest dimension of babies head distends vulva
▪ Episiotomy may be done to reduce tissue tearing
◦ Placental Stage
▪ Delivery of placenta and its attached fetal membranes
▪ Usually within 30 minutes after birth
Genetics
• Nuclei of all human cells except gametes contain the diploid number of chromosomes (46)
consisting of 23 pairs of homologous chromosomes
• Two are the 46 are sex chromosomes which determine the genetic sex
• The other 44 are 22 pairs of autosomes that guide the expression of other traits
• Diploid genome makeup represents two sets of genetic instructions, one from egg, other from
sperm
Types of Inheritance
• Dominant- recessive inheritance
◦ Reflect the interaction of dominant and recessive alleles
◦ Punnett square is used to determine the possible gene combinations for a single trait that
would result from the mating parents of known genotypes
▪ Only predicts the probability of particular genotypes
▪ Larger number of offspring means a greater chance that ratios will conform to the
prediction
▪ Production of each child is an independent event and does not effect the outcome of the
next child
◦ Dominant traits- human traits dictated by dominant allels includes widows peak, dimples,
freckles
▪ Huntington's disease
◦ Recessive traits- recessive traits include normal vision
▪ Albinism, cystic fibrosis, Tay- Sachs disease
▪ Recessive genetic disorders are more frequent because those who carry a single
recessive allele for a recessive genetic disorder do not express the disease but can pass
the disease on
▪ Few individuals will dominant traits live long enough to pass the trait on
◦ Incomplete dominance- the heteroxygote has a phenotype intermediate between those of
homozygous recessive individuals
▪ Sickling gene- individuals who have double does of the sickling allele have sickle cell
anaemia, those who are heterozygous for the sickling gene have sickle- cell trait
• Multiple Allele Inheritance
◦ Some genes exhibit more than two allele forms
◦ Co-dominant genes are both expressed when present
Nontraditional Inheritance
• Beyond DNA- Regulation of Gene Expression
◦ Three basis levels of gene control- protein coding genes (1st level), small RNAs (2nd level),
epigenetic marks (3rd level)
◦ Smalls RNAs
▪ Product of abundant RNA only genes found on non-protein coding DNA, form parallel
regulatory system that generates single-stranded microRNAs and short interfering RNAs
▪ These small RNA can act directly on DNA or RNA and can tame transposons
▪ Small RNA control timing of programmed cell death during development and can also
prevent translation of another gene
◦ Epigenetic marks
▪ Continually changing information is stored in proteins and chemical groups that bind
DNA
▪ Chemical tags within cells determine whether DNA is available for transcription or
silenced.
▪ Also accounts for inactivation of one of females X chromosomes in the early embryo
▪ Underlies genomic imprinting which tags genes as paternal or maternal and confers
important functional differences in the embryo
• Extranuclear Inheritance
◦ Not all genes are in the nuclues, 37 genes are in mitochondria and are transmitted almost
exclusively by mother
future
• Blood tests- can detect presence of other unexpressed recessive genes
• Fetal testing
◦ Used when there is a known risk of genetic disorder
◦ Most common type is aminocentesis
▪ Fluid is drawn from amniotic sac and checked for enzymes and other chemicals that
serve as markers for certain disease
◦ Chorionic villus sampling- suctions off bits of the chorionic villi from placenta for
examination
• Human gene therapy
◦ Human Genome Project has allowed research on diagnosis of genetic disease and on its
treatment to improve
◦ Single gene disorder correction is fairly successful
◦ Most common approach is transferring a corrected gene via a virus to affected cells to
restore normal function