Anatomy Lecture Exam #3

Hemopoiesis

- The process of blood formation sometimes called hematopoiesis. o Formed elements of blood are constantly being produced and recycled. •Cells and platelets have a relatively short lifespan (about 120 day for RBCs), also lose some through bleeding. •Very different than most tissues of the body. o Body produces a STAGGERING number of new cells each day. •400 BILLION platelets. •100-200 billion RBCs. •10 billion WBCs. o New formed elements don't come from pre-existing RBCs, WBCs, or platelets. •Mature, circulating cells don't undergo mitosis. •Formed elements are produced in hemopoietic tissues where stem cells reside.

Hemoglobin (Hb)

1 "protein" made of 4 polypeptides: 2 alpha chains, 2 beta chains. •Each chain contains an iron (Fe2+) group called a HEME group. •O2 binds to the heme group of hemoglobin. -Each Hb molecule can transport 4 molecules of O2. •Cooperative binding - When O2 binds to one heme this makes it easier for O2 to bind to the other 3 heme groups. •Competitive binding - Other molecules can also bind to heme group (i.e, they compete). -Carbon monoxide, cyanide prevent O2 from binding (poisonous).

Several very large blood vessels are attached at the base of the heart (great vessels).

1. Aorta - carries oxygenated blood from the left ventricle out to systemic circ. 2. Inferior and superior vena cava - returns deoxygenated blood back to the heart from the systemic circ.

Blood pressure is regulated primarily by three factors:

1. Cardiac output - increased CO leads to increased BP. 2. Blood volume - increased blood volume increases BP. -Largely controlled by kidneys (hydration and Na+ plays a big role). -Dehydration reduces amount of water in plasma → less blood volume. -Na+ causes you to retain water → more water in plasma → more blood volume. 3. Resistance in blood vessels - caused by friction between blood and vessel walls.

Two main functional divisions exist:

1. Conducting division - •Structures which allow air to get to lungs, but do not exchange O2 and CO2. •Nose, pharynx, larynx, trachea, most bronchi. 2. Respiratory division - •Portion of resp. system that carries out gas exchange. •Some smaller distal bronchi and alveoli.

Leukocyte disorders

1. Leukopenia - abnormally low WBC count. •Can be caused by heavy metal poisoning (mercury, lead), radiation exposure, some viral infections. •Very common side effect of glucocorticoid therapies, anti-cancer therapy, and immunosuppressive therapy for organ transplant recipients. 2. Leukemia - very HIGH numbers of WBCs. •Can occur in either myeloid or lymphoid tissues and either be acute (rapidly developing) or chronic (more slowly developing). •A very serious type of cancer since cancerous leukocytes will overpopulate the marrow and prevent normal leukocytes, RBCs, and platelets from maturing. •Many patients die from opportunistic infections or hemorrhage due to lack of platelet function.

Agranulocytes

1. Lymphocytes: •Very common, (25-30% of WBCs). •Usually have a large, rounded nucleus that takes up most of the cell - only a small amount of cytoplasm is visible. •Three different classes (T-cells, B-cells, NK-cells), but all look pretty similar - usually differ slightly in size. •Play various roles including coordinating immune responses and producing antibodies that "flag" invaders and damaged. 2. Monocytes: •Largest of the WBCs, make up 3-8% of all WBCs. •Nucleus usually takes on a U-shape or kidney bean shaped appearance. -Less obvious in very large monocytes, but certainly can distinguish from a lymphocyte since monocytes are much larger overall. •Numbers of monocytes increase rapidly in response to infection. •Monocytes will further differentiate into macrophages and hang out in tissues where they phagocytose pathogens and damaged cells.

Respiratory system anatomy

1. Nose 2. Pharynx •nasopharynx, oropharynx, laryngopharynx. 3. Larynx 4. Trachea 5. Bronchi - airways within the lung 6. Lungs •Most distal portions end in sacs called ALVEOLI. •How we get O2 from atmosphere to blood. -Essentially a "dead end" circuit - air enters resp. system, travels to distal parts of lung, then goes back the way it came in.

One complete heartbeat or cardiac cycle

1. P-wave - represents the depolarization of the SA node and subsequent depolarization of the atria. 2. QRS complex - represents the depolarization of the AV node and then the ventricles. 3. T-wave - represents the repolarization of the ventricles. •NOTE - the repolarization of the atria is not seen on an EKG since the larger QRS complex masks it...

CV system consists of two main divisions based on where the blood is going after leaving the heart

1. Pulmonary circuit - carries blood that is O2-poor/CO2-rich to the lungs so that O2 and CO2 can be exchanged, returning O2-rich/CO2-poor blood back to the heart so it can enter the systemic circuit. 2. Systemic circuit - carries O2-rich/CO2-poor blood from the heart out to all of the tissues of the body, THEN carries the O2-poor/CO2-rich blood back to the heart so that it can enter the pulmonary circuit. •The right side of the heart pumps blood through the pulmonary circuit....left side of the heart pumps blood through the systemic circuit

All arteries and veins consist of three layers or TUNICS

1. Tunica intima - endothelial cells and basement membrane. 2. Tunica media - thickest layer consisting of collagen, smooth muscle. •This layer is thicker in arteries and often contains elastic tissue - higher fluid pressure in arteries than veins. •Smooth muscle allows vessels to alter diameter - important for regulating blood flow and pressure. 3. Tunica externa - loose connective tissue that helps anchor vessels to tissues, other vessels. •Tissues of small vessels exchange nutrients, wastes, gases by diffusion from bloodstream üLarger vessels possess VASA VASORUM.

Blood flow and pressure example

1. Two tissues each weigh 50 g and receive 20mL of blood per minute. •(FLOW and PERFUSION are the same between the two tissues). 2. Tissue A weighs 50 grams and Tissue B weighs 200 grams and both receive 50 mL of blood per minute. •FLOW is the same but PERFUSION is not! •A = 1mL/min/g •B=0.25mL/min/g 3. Tissue A weighs 50 grams and receives 50mL of blood per minute. Tissue weighs 25 g and receives 25mL/min. •Perfusion is same in both (1mL/min/g), but Flow is not!

Granulocytes

1.Neutrophils: •Most abundant of WBCs (60-70% of all WBCs). •Nucleus appears to have several lobes (3-5 per cell). •Function to kill bacteria/viruses: -Phagocytosis (slow). -Can secrete chemicals that kill pathogens in vicinity of neutrophil (stored in granules within cell). •When bacteria/viruses are present, neutrophil generates lots of oxygen free radicals which are then used to create H2O2 (hydrogen peroxide), and sodium hypochlorite (bleach). •These chemicals are stored in granules and then released (degranulation). •These chemicals kill everything around the neutrophil (including the neutrophil itself).

Granulocytes part 2

2. Eosinophil: •Far less abundant (2-4% of WBCs). •Many more reside in membranes of respiratory, digestive, and urinary tract. •Nucleus appears to have 2 lobes. •Function to phagocytose antigen-antibody complexes, allergens, inflammatory cytokines (help limit inflammation). •Proliferation of eosinophils is triggered by allergic reactions, parasitic infections. •Like neutrophils, eosinophils can generate oxygen free radicals that are stored in granules and released to kill pathogens. 3. Basophils: •Very rare type of WBC (less than 1% of WBCs). •Large number of dark staining granules prevents nucleus from being seen. •Play an important role in wound healing and coordinating immune response to infections and inflammation. -Secrete histamine (a vasodilator) that allows more WBCs to get to sites of infection, injury. -Secrete heparin (an anticoagulant) that temporarily prevents blood clot formation (also allowing more WBCs to get where they need to be).

Principles of pressure, blood flow, and the cardiac cycle

A given amount of fluid will occupy a certain volume at a particular pressure. •Assuming there is no outlet to relieve the pressure. -As the volume of a space increases, the pressure decreases. •As the volume of a space decreases, the pressure increases. •PRESSURE GRADIENTS (the difference in fluid pressure between two areas) dictate when and under what pressure fluid will move between two places üThese principles govern how blood moves between chambers and vessels. -Ex. #1 As the pressure inside the right ventricle increases (contraction) blood is forced into the lower pressure area of the pulmonary trunk. -Ex. #2 As the pressure inside the right ventricle decreases (relaxation) blood flows from the area of higher pressure (atrium) into the area of lower pressure (ventricle).

The Electrocardiogram (EKG or ECG)

An EKG measures electrical activity throughout the cardiac cycle. •Electrodes positioned on the wrists, ankles, and chest send info on electrical activity to an electrocardiograph. •Each peak on an EKG represents the depolarization or repolarization of a certain portion of the heart.

RBC and Hemoglobin disorders

Anemia: Disease of low RBC # or low Hb levels hypoxia 3 types: 1. Caused by deficient erythropoiesis or Hb synthesis by erythroblasts. 2. Hemorrhagic anemia - caused by bleeding. 3. Hemolytic anemia - caused by excessive RBC destruction. 4. Pernicious anemia - caused by lack of Vit B12/Intrinsic Factor. Polycythemia: overproduction of RBCs. Sickle cell disease: (anemia). •Individuals contain a mutated Hb gene (HbS). •HbS tends to polymerize into long rods - can't carry O2 efficiently (especially at low oxygen concentrations). •Sickle cells often clump together and clog blood vessels. •Disease requires both Hb genes to be mutated (homozygous recessive). •A "carrier" = person with one good and one mutated Hb gene. ½ Hb is mutated, ½ is OK. •Actually gives person resistance to malaria. •Mutation is in ONE nucleotide (GAG → GTG)....leads to substitution of glutamate → valine.

Blood Vessels

Arteries carry blood FROM the heart. -Decrease in size with distance from heart. -Very small arteries = ARTERIOLES. •Veins carry blood TO the heart. -Increase in size closer to heart. -Very small veins = VENULES. •Capillaries microscopically thin vessels where nutrients, gases, wastes are exchanged with tissues -Essentially link arterial system with venous system.

Chambers and valves of the heart

Atria are chambers that receive blood from lungs or rest of body. Ventricles are chambers that expel blood to the lungs or rest of body. •Atria and ventricles are separated by a muscular wall called a septum. •Atrioventricular (AV) valves prevent backflow of blood from ventricle into atrium. -Tendinous cords and papillary muscles prevent valve prolapse. •Pulmonary and aortic valves ("semilunar valves") and AV valves ensure one-direction blood flow. •Faulty valves cause blood to flow back into atria (AV valves) or ventricles (semilunar valves). •Increased pressures in these chambers force heart to contract more forcefully ...more strain on heart. •Faulty valves often are the cause of heart murmurs (abnormal heart sounds).

Autonomic control of heart rate

Cardiovascular control centers in the brainstem receive info from various parts of the body and direct appropriate changes in HR. • Excellent example of a FEEDBACK LOOP.

Pacemaker physiology

Cells of the SA node will rhythmically fire action potentials without any nerve stimulation and allows heart to beat about every 0.8 sec........But how???? •Remember depolarization requires flow of (+) ions into the cell. -Normally accomplished by opening of ligand- or voltage-gated ion channels. •SA node cells contain 3 important ion channels : Na+ channel, Ca2+ channel, K+ channel. •Some Na+ channels are constantly open (Na+ is flowing into the cell) allowing cell to VERY SLOWLY approach a depolarized state. •When the cell reaches an electrical threshold, LOTS AND LOTS of voltage-gated Ca2+ channels open and Ca2+ rushes in causing rapid depolarization of the cell. •Soon, K+ channels open and K+ quickly leaves the cell allowing it to become repolarized. •BUT!! Na+ channels are still open and slowly depolarizing the cell AGAIN!!! •This cycle allows SA node cells to depolarize rhythmically without stimulation.

Complete blood count (CBC)

Collection of clinical tests designed to assess number and condition of formed elements in blood. •Gives information on # of RBCs, platelets, WBCs. •Hematocrit measures packed cell volume (estimates # of RBCs). •Differential WBC count determines the # of various types of WBCs. -Changes in the # of WBCs often indicate disease (infection, inflammation, cancers, etc). •May also look at morphology (shape) of cells. -Odd shaped cells indicate disease (sickle cell anemia).

Cardiac rhythm and contraction cont.

Conduction of signal occurs very rapidly across atria...allows atrial tissue to contract uniformly. •Ventricular cardiomyocytes receive signal to contract in one of two ways. 1. Signal is received via intercalated disks from a nearby cell (slower). 2. Signal is receive directly from purkinje fibers (faster). •Ventricles are quite large and thick with many more cells than in atria. -Purkinje fibers allow signal to get to most of the ventricle much faster than only by diffusing through intercalated disks.

Cardiac rhythm and contraction

Coordinated contraction and relaxation of atria and ventricles are essential to efficient pumping of blood through pulmonary and systemic circuits. •Prevents overload of circuits - elevated pressures. •SYSTOLE = contraction of chambers, ejects blood. •DIASTOLE = relaxation of chambers, allows filling of chambers with blood. •All 4 chambers DO NOT contract at same time!!! -BOTH atria contract first, both ventricles contract shortly after. •Depolarization begins at SA node → causes atria to contract first. •Signals travel to AV node and then on to the ventricles. → delay causes ventricles to contract shortly after atria ---- about 100 msec after atria contract. •This delay is VERY important because it allows ventricles time to fill with blood.

Coronary circulation

Coronary arteries and cardiac veins supply blood to the tissues of the heart. Pattern is quite variable from person to person. •Most major vessels run along AV sulci and interventricular sulci. •Most coronary venous blood drains into CORONARY SINUS and then into Rt. Atrium. •Arterial blood comes from 2 coronary arteries that branch directly off of aorta and then give off multiple branches. •Clots in coronary blood vessels cause myocardial infarction.

Cardiac output

Defined as the amount of blood ejected from the heart each minute. Mathematically: • Stroke volume (SV) X Heart rate (HR) in beats per minute = Cardiac output (CO) • So, for a normal resting person..... 70 mL X 75 beats per minute = 5,250 mL/min •Since most people have about 5L of blood, all of the blood in the body passes through the ENTIRE pulmonary and systemic circuits every single minute. •CO will vary slightly from person to person (variations in stroke volume, resting heart rate). •CO is affected by exercise and condition of individual. -Exercise elevates HR → increased CO (most people can increase CO by ~400%...CARDIAC RESERVE). -Well trained athletes often have increased SV.

Blood Pressure

Defined as the force that blood exerts on the wall of a blood vessel. Blood pressure (BP) is most commonly measured within the brachial artery with a sphygmomanometer and is referred to ARTERIAL BP. •A "healthy" BP in an adult is about 120/80 mm Hg. •PULSE PRESSURE is the difference between systolic and diastolic pressures (40 mmHg for "normal" BP). •MEAN ARTERIAL PRESSURE measures the average pressure within an artery over a given period of time (if you measured BP once every 1/10th of a second for 1 second). Not a simple average (i.e., (120 + 80) / 2 = 100 mm Hg -Diastole lasts longer than Systole!! -So, a good estimate = Diastolic pressure + 1/3 of pulse pressure 80 + (40/3) = 93.3 mm Hg.

5 types of WBC

Differ in appearance , number, and in function.Fall into two main categories: 1. Granulocytes: contain many lysosomes and organelles (i.e., granules) that stain darkly on a microscope slide. a) Neutrophils b) Eosinophils c) Basophils 2. Agranulocytes: no visible granules. a) Lymphocytes b) Monocytes

Heart Rate Regulation

Easily measured by counting pulsations in a superficial artery (pulse). "Normal" resting heart rate is around 75 beats/min. •Tachycardia - resting heart rate about 100 beats/min. -Can be result of stress, drugs, heart disease, etc... -Can also compensate for low SV. •Bradycardia - resting heart rate below 60 beats/min. -Common during sleep, and in very well trained athletes -Can also be caused by some medications (depressants). •Factors (hormones, drugs, etc..) that change the HR are known as CHRONOTROPIC AGENTS: -Positive chronotropic agents INCREASE rate. -Negative chronotropic agents DECREASE rate.

Pharynx

Fivided anatomically into 3 regions: 1. Nasopharynx - posterior to the nasal cavity, slightly superior to oral cavity. Lined by mucus membrane •Lymphoid tissues (tonsils) located here are exposed to inhaled particles/pathogens. •Eustachian tube (auditory tube) opens here. 2. Oropharynx - posterior to the oral cavity, inferior to the soft palate (roof of mouth). •Also well supplied with lymphoid tissues. 3. Laryngopharynx - inferior to oropharynx. •Laryngopharynx and oropharynx transmit BOTH food/liquid and air. •Lined by non-keratinized, stratified squamous epithelia. -Nasopharynx ONLY transmits air. •Lined by pseudostratified columnar epithelium.

Circulatory system regulation

Fluids can be released into or absorbed from tissues to help regulate fluid distribution throughout body. •Blood contains buffers that help stabilize pH of body tissues. •Dilation and constriction of blood vessels are important for thermoregulation.

Balanced ventricular output

Imbalances in ventricular output lead to abnormal blood pressures in the pulmonary and systemic circuits. •If RV output exceeds LV output (failure of left ventricle), blood backs up in the lungs → pulmonary edema. -Under high pressures fluid escapes from blood vessels and accumulates in tissues. •So, if the RV ejects 60 mL of blood into the lungs, the LV needs to be able to accept 60 mL of blood from the left atrium (which is receiving blood from the lungs. •Pulmonary edema is a serious complication of cardiovascular disease. •Often the result of LV failure (less ejection means less filling). •Patients have extreme difficulty in breathing and cough up blood.

Normal v. damaged contraction

In a normal heart rhythm, the contraction is triggered by the SA node, spreads throughout atria → AV node → bundle fibers, purkinje fibers→ spreads throughout ventricle. -SINUS RHYTHM •Damage to conduction system (SA node, AV node, bundle branches, purkinje fibers) alters heart rhythm and is known as HEART BLOCK. •Some electrolyte imbalances, drugs, or damage to the SA node can cause part of heart to depolarize BEFORE SA node fires (either the atria or ventricles). -ECTOPIC FOCUS. -Often causes FIBRILLATION. •Any heart rhythm where depolarization initiates away from the SA node is an ARRHYTHMIA.

Respiratory system function and anatomy

In biology, RESPIRATION can have several meanings: 1. Movement of air in/out of the lungs (really known as ventilation). 2. Exchange of O2 for CO2 in the bloodstream. 3. Use of O2 during aerobic respiration (ATP generation).

Circulatory system protection

Inflammatory agents and cells in blood help coordinate wound healing and contain infections. •Immune cells (leukocytes) work together to clear infections by bacteria, viruses, parasites. •Phagocytosis, antibody production, secretion of cytotoxic chemicals. •Clotting factors and platelets coordinate formation of blood clots, limit blood loss.

Regulation of blood pressure depends on a constant series of NEGATIVE FEEDBACK LOOPS

Involves sensors and receptors in body, cardiovascular control centers in brainstem, as well as many EFFECTORS: heart, blood vessels, kidneys, etc... all working together to maintain homeostasis •Keep in mind that this loop can go in BOTH directions depending if BP is too high or too low!!!

Heart Sounds

Listening to the sounds of the body (heart, lungs, etc...) is known as AUSCULTATION, an Important part of a physical exam. •Normal adult heartbeat has two sounds "LUBB....DUBB". •First sound is caused by closing of AV valves during ventricular systole (lubb). •Second sound is caused by closing of semilunar valves during diastole (dubb). -Abnormal heart sounds often indicate damaged or impaired AV or semilunar valves.

Proprioceptors

Mechanical sensors in joints and muscles tell cardiac center to increase HR (via sympathetic division of ANS). - these sensors detect movement of limbs.

Alternative forms of Hb

Most adult Hb is known as HbA, contains 2 alpha chains and 2 beta chains. •A small amount (~3%) is known as HbA2, containing 2 alpha chains and 2 delta chains - not a big deal physiologically. Fetuses contain a different type of Hb known as fetal hemoglobin (HbF). •Disappears shortly after birth. •HbF has a greater affinity for O2 than HbA. •Allows fetal blood to "steal" O2 from mother's bloodstream and deliver it to the fetus.

Control of stroke volume

Other way to regulate cardiac output is by changing stroke volume. Stroke volume is influenced by three factors: 1. Preload - amount of blood in ventricles (EDV) dictates stroke volume. •Remember ventricle needs to eject as much blood as it receives. •STARLING LAW OF THE HEART basically says that the more you stretch the heart (larger EDV), the more forcefully it will contract (TO A CERTAIN LIMIT!!!!). •Unlike skeletal muscle, resting cardiac muscle is not naturally at optimal resting length.....so some stretching is good for contraction. 2. Contractility - describes the force with which the heart contracts for a given PRELOAD. •Positive and negative INOTROPIC agents increase or decrease contractility of heart. •Ca2+ and agents that increase Ca2+ levels make the heart muscle cells contract more forcefully (more myosin heads binding to active sites on actin). •Elevation in Ca2+ also lengthens the plateau phase of cardiac muscle cell depolarization (longer contraction). •Ca2+ channel blockers reduce CO by decreasing force of heart contraction.....sometimes used to treat hypertension, heart disease. 3. Afterload - describes the pressure of blood "after" the heart beats. •Basically the amount of blood pressure in the pulmonary trunk or aorta. •A very large afterload limits how much blood the ventricles will be able to eject into the circulation. •Afterload is very high in pulmonary and systemic hypertension. -Eventually, ventricles have to beat so hard to overcome afterload, that they fail.

All formed elements can be traced back to a pluripotent stem cells.

Platelets are fragments of a larger cell called a megakaryocyte (which also can be traced back to a pluripotent stem cell).

Platelet formation

Pluripotent stem cells mature into megakaryocytes. •Huge cell that is actually visible to the naked eye. •Maturation of megakaryocytes can be triggered by several factors: -Thrombopoietin , inflammatory cytokines, EPO. •Following maturation, the platelets bud off from the large megakaryocyte. -One megakaryocyte can produce 1000's of platelets. -Platelets have a very short lifespan (~10 days).....so platelets need to be constantly produced.

Baroreceptors

Pressure receptors located in various parts of the body that send info to cardiovascular centers. •Elevation in blood pressure causes decrease in HR. •Decrease in blood pressure causes increase in HR.

Rh blood group

RBCs also may contain an antigen known as the Rh antigen. -Either you have it or you don't → i.e, Type A positive (A+) or A negative (A-), etc. •Unlike ABO antigens, our plasma normally doesn't have any antibodies against Rh antigen. -unless we are exposed to Rh antigen. 1. Rh+ blood into an Rh- person. 2. Rh- mother carrying an Rh+ fetus (small amt of blood is exchanged during childbirth). -Production of Rh antibodies is slow, so first exposure (transfusion, or pregnancy) is ok. -However, second pregnancy can be a problem. -Mother's anti-Rh antibodies may pass into fetal circulation causing fetal blood to agglutinate. -Today most pregnant Rh- women receive an injection of anti-Rh antibodies that will bind up any Rh+ cells she is exposed to......this prevents her own immune system from producing Rh-antibodies,

Chemoreceptors

Receptors that sense levels of CO2, 02, and pH. •CO2 in blood gets converted to carbonic acid (lowers blood pH) - need to get rid of CO2 through the lungs → increase in HR. •Low O2 levels also increase HR.....need to pump more blood to satisfy tissue needs for O2.

Osmolarity

Refers to the concentration of dissolved molecules in the blood (mainly proteins and electrolytes). •High osmolarity leads to removal of water from tissues→hypervolemic hypertension. •Low osmolarity prevents water from leaving tissues → edema (swelling of tissues). •Electrolyte levels are mainly regulated by kidneys. -Kidney disease, dehydration, diarrhea can alter levels. •Liver produces most plasma proteins. -Liver disease can lead to reduced osmolarity of blood → accumulation of fluids in tissues (edema). •Severe dietary protein deficiency → kwashiorkor.

Platelets

Relatively small proportion of whole blood (~1% of formed elements). •Are actually small fragments of larger cells known as megakaryocytes. -No nucleus, but do have lysozomes and a number of other organelles and granules. •Carry out a variety of functions: 1. Secrete vasoconstrictors - cause blood vessels to constrict. 2. Stick together to form a platelet plug. 3. Secrete factors that promote clotting (early) as well as clot dissolving substances (late). 4. Secrete chemicals and growth factors that attract neutrophils and monocytes, as well as cause proliferation of fibroblasts (wound healing). 5. Can also act as phagocytes (not their main function).

Cardiovascular system

Remember that the cardiovascular system refers to the (1) heart and the (2) blood vessels.

Trachea

Rigid tube found ANTERIOR to the esophagus, continuous with inferior part of larynx. •C-shaped rings of hyaline cartilage offer structural support. -Rings get smaller, thinner as you go deeper into the lung tissue (more distal). •Interior lined by pseudostratified columnar epithelium and many GOBLET CELLS (mucus cells). -Particles get trapped in mucus and cilia on columnar cells sweep upwards. -Dirty mucus gets moved towards esophagus where it can be swallowed. -Referred to as the MUCOCILIARY ELEVATOR.

Erythrocytes (red blood cells)

Round, disc shaped with an indentation in the center. •2 main jobs: 1. Carry O2 from lungs to tissues. 2. Carry small amount of CO2 from tissues to lungs (most CO2 is dissolved in plasma). •One of the only cells in the body without a nucleus •Basically are disc shaped bags of hemoglobin. -No nucleus, DNA, organelles (lost during development). -Can't carry out protein synthesis or cell division. -Without mitochondria they make energy via anaerobic fermentation. •Interior of cell is supported by small amount of ACTIN and spectrin (allows RBCs to squeeze through small capillaries and venules). •RBCs do contain some enzymes that function to buffer pH.

Ventricular fibrillation

Signals are not carried through the conduction system normally, causes ventricle to quiver or flutter. •Blood is not pumped efficiently →no systemic circulation→ no coronary circulation (myocardium dies quickly). •Abnormal rhythm can often be corrected in a number of ways: 1. Anti-arrhythmic drugs. 2. Cardioversion - delivery of an electrical shock at a very specific time of the cardiac cycle. 3. Defibrillation - normally only done in extreme circumstances. Large shock of electricity depolarizes the ENTIRE HEART at the same time. •Hope is that normal sinus rhythm will resume - like a "reset" button

Signal conduction through the heart

Sinoatrial node (SA node) is a patch of cells in the right atrium known as the "pacemaker" of the heart. •SA node cells depolarize much easier than other muscle cells and will spontaneously depolarize at regular intervals. •Depolarization of SA node triggers depolarization of both atria. -Intercalated disks are critical. •Atrioventricular node (AV node) is another patch of cells lying near the bottom of the interatrial septum -Detects depolarization of atria and sends signal that triggers depolarization of ventricles. •Fibers from the AV node travel down the interventricular septum and split into right and left bundle branches, then travel up along the surface of both ventricles. •These branches give off modified nerves called PURKINJE FIBERS that stimulate the entire ventricle to contract. -The depolarization (electrical activity) of different parts of the heart are detected and reported on an ELECTROCARDIOGRAM (ECG).

Influence of ANS on heart rate: Heart Rate Acceleration

Sympathetic nerve fibers travel from medulla oblongata to SA node, AV node, and myocardium. •Nerve fibers release norepinephrine that binds to β-adrenergic receptors. -Norepinephrine increases HR. -"Beta-blockers" are often prescribed to treat hypertension - reduces heart rate and therefore CO and therefore BP.

Formed elements of blood

The 7 visible structures in blood. A. Erythrocytes. •Transport O2 and CO2 (a little). •95% of formed elements. B. Platelets (small cell fragments). •Critical for clotting, wound healing. C.Leukocytes 1.Neutrophils 2.Eosinophils 3.Basophils 4.Lymphocytes 5.Monocytes

Plasma

The ground substance of blood (remember blood is connective tissue). •Mostly water (<90%) the remaining 10% is: -Nutrients :glucose, amino acids, lipids, etc... -Electrolytes :Na, Ca, K, Cl, etc... -Nitrogenous waste (byproducts from metabolism). -Gases (O2, CO2, N2 ). -Enzymes. -Hormones (many). -Plasma proteins (most produced by liver). -Albumin - helps pull water into circ. system, acts as a carrier for some hormones, drugs, lipids. -Globulins-generic term for many proteins (including antibodies). -Fibrinogen - converted to fibrin, critical for blood clotting.

Pericardium

The heart is contained within a double-layered sac known as the PERICARDIUM. •PARIETAL PERICARDIUM is the outer layer. -Consists of a outer fibrous layer and an inner serous layer. •VISCERAL PERICARDIUM is the inner layer closest to the heart (also known as the EPICARDIUM). -Basically a continuation of the serous layer of the parietal pericardium. •Between the two layers is the PERICARDIAL CAVITY. -Filled with PERICARDIAL FLUID that allows the heart to operate in a low friction environment.

Nerve supply of the heart

The heart is innervated by both divisions of the autonomic nervous system which allows us to regulate rate and force of heart contraction. 1. Sympathetic division - generally increases force and rate of contraction, as well as increasing blood flow through coronary blood vessels. •Important for "fight or flight" response. 2. Parasympathetic division - generally reduces heart rate. •Main influence is through the VAGUS NERVE (CN X). •Innervation by ANS is important for REGULATION of rate and force of contraction, BUT heart will still beat even if all innervation is removed. -Heart will naturally beat at about 100 beats/min without innervation. -Regular, rhythmic beating of the heart is stimulated by SINOATRIAL NODE of the right atrium.

Heart Wall

Three layers: 1. Epicardium (visceral pericardium) - a simple layer of squamous epithelia directly on the surface of the heart. 2. Myocardium - thickest layer composed of the cardiac muscle cells that carry out contraction. 3. Endocardium - another simple layer of squamous epithelial cells lining the interior of the heart and valves. •These three layers make up the wall of each of the 4 chambers of the heart. -2 upper atria, 2 lower ventricles. -Thickness of the walls will vary.

Circulatory system transport of a variety of chemical products, cells, and energy (heat)

Transport of a variety of chemical products, cells, and energy (heat). •Carries O2 and CO2 back and forth from lungs to tissues. •Carries nutrients from GI tract to tissues and metabolic wastes to the kidney for excretion. •Carries hormones from glands to effector organs and tissues. •Carries immune cells throughout the body to sites of infection. •Transports heat to skin surface for release when needed (thermoregulation).

Blood composition

Two main components : Plasma (55%) and Formed elements (45%). •"Average" person has about 5L of blood (8-10% of body weight).

Erythrocyte recycling

Typical lifespan of RBC is 120 days: •Cell membrane gets more fragile with age. •Spleen is key organ in RBC recycling. -Blood is forced through VERY small passageways in spleen. -Old, fragile RBCs get trapped and are broken down. •Bilirubin is a by-product of hemoglobin breakdown -Bilirubin is removed from bloodstream by liver - ends up in digestive system (gives feces its color). -Liver disorders can cause JAUNDICE. -Bilirubin accumulates in bloodstream causes skin to look yellowish.

EPO and RBC productio

Typical negative feedback loop. •Body senses abnormally low O2 levels and takes steps to increase # of RBCs allowing more O2 to be carried in bloodstream. -Body assumes that low RBC # is the cause of the hypoxemia (not always true). -Smokers with emphysema have chronic hypoxemia - body reacts by constantly making more RBCs (POLYCYTHEMIA). -Living at high elevations (less oxygen in air) can also trigger RBC production.

Blood viscosity

Viscosity basically refers to the "thickness" or "stickiness" of blood. •Thick fluids have greater viscosity, thin fluids have less -Consider viscosity of honey versus wate. •Affects flow through small vessels (venules, capillaries). •Variations in # of cells (RBCs, WBCs), body temperature, and protein content affect viscosity. -Polycythemia (too many RBCs), some leukemias (WBCs). -Hypothermia - contributes to limited blood flow to extremities. •High OR low viscosity has negative consequences. -Low viscosity can trigger over-perfusion, damage to capillaries, venules. •High viscosity can limit perfusion, damage vessels. •Both cause excess strain on heart.

Water distribution in body

Water is distributed between three "compartments". •Intracellular, extracellular (interstitial), and plasma. •Osmolarity determines distribution of water in these compartments.

Larynx

a.k.a. the "voicebox". •Obviously hugely important for its social and psychological function. •Also very important for keeping food, fluids out of the airways. -Epiglottis - larynx is PULLED upwards when we swallow and closes opening of larynx. -Vestibular folds - also close shut when we swallow. •Very well protected by a number of thick cartilage structures. -Thyroid cartilage - forms "Adam's Apple". •Cricoid cartilage - connects larynx to trachea below. -Many smaller cartilages that are important for vocal portion of larynx.

Leukopoiesis

•All WBCs develop from pluripotent stem cells and begin development in red marrow. •Stem cells mature into WBC colony forming cells (CFUs) which have receptors for hormones and growth factors that trigger their further development. •Some specific growth factors are released by MATURE WBCs in response to allergens, pathogens, etc. •Some immature lymphocytes migrate to LYMPHOID tissues (thymus, spleen) to undergo final maturation. •Other WBCs stay in red marrow until needed.

Circulatory Routes

•All blood leaving heart eventually needs to return. •This is accomplished in several different ways. •Most common way is from L.V. → artery → capillary bed → vein → R.A. •In a PORTAL SYSTEM, blood flows through TWO capillary beds prior to returning to the heart. -Usually these two capillary beds are in different organs. •In an ARTERIOVENOUS SHUNT, blood is able to be "re-routed" and bypasses the capillary bed. -Blood flows directly from arterial system to venous system. -Helps regulated flow to specific organs/tissues. •ANASTAMOSES - location where several arteries or veins converge/diverge before or after a capillary bed. -Allows blood to enter or exit a capillary bed by more than one route.

ABO blood typing

•All cells in our bodies have a variety of cell-surface proteins that identifies them as belonging to us (surface antigens). •RBC antigens don't vary as much. •A, B, and O antigens differ in monosaccharide attached to galactose. -"O" antigen does not have the extra monosaccharide attached to galactose. •If we receive the wrong type blood, antibodies in our plasma will bind to the foreign cells and cause them to clump together (agglutination).

Veins

•Also known as CAPACITANCE VESSELS since they can accommodate large volumes of blood by expanding (~65% of blood is on venous side of circulation). •Relatively thin walled, with little smooth muscle. -Don't need to withstand high pressures like arteries. •Also broken down roughly on the basis of size: 1. Venules - smallest veins that drain blood from the capillary bed. Somewhat porous like capillaries and allow leukocytes to exit into tissues. 2. Medium veins - mid-sized veins such as ulnar or tibial veins. üContain valves that prevent low pressure venous blood from flowing backwards. 3. Venous sinuses - very thin walls with no smooth muscle (i.e., Coronary sinus). 4. Large veins - Relatively small amount of smooth muscle, but large diameters. -Sup. and inf. vena cava, common iliac veins, common jugular are examples.

Cardiac muscle

•Although purkinje fibers carry the electrical signal, not every cell is DIRECTLY stimulated by these fibers. •Cardiac muscle cells (cardiomyocytes) are linked to each other by INTERCALATED DISKS. •These connections are VERY strong and contain gap junctions that allow signals to rapidly pass from one cell to the next. -So...contraction of one cell can trigger contraction of other cells nearby, and so on, and so on. •Allows the heart to contract in coordinated fashion. -Allows for efficient ejection of blood from one chamber to the next.

Atrial fibrillation

•Atrial fibrillation (A-fib) occurs when depolarizations occur at areas other than the AV node. Causes atria to flutter or quiver. •Often goes undetected since adequate amounts of blood often still enter the ventricles. •Normally not immediately life-threatening, episodes can come and go, but can be chronic. •Dramatically increases risk of stroke due to formation of blood clots. -Clots could eventually get pumped out of the heart. -Many people with diagnosed A-fib take anticoagulants each day (Coumadin is an anticoagulant drug).

Blood pressure varies with distance from heart and between arteries and veins

•Blood in larger arteries (closer to heart) is under very high pressure and is PULSATILE - pressure varies with phase of cardiac cycle. •However, arteries expand during systole and absorb some pressure thereby reducing pressure as you get farther from the heart. -As a result, pressure in your brachial artery will be greater than in an artery in your foot. •As blood flows through smaller and smaller arteries, more pressure is absorbed so that blood returning to the heart is under very LOW pressure. -Venous blood flow is generally not pulsatile.

Arterial Sense Organs

•Blood is very closely monitored for pressure and chemistry to maintain homeostasis. •BARORECEPTORS - monitor blood pressure. •CHEMORECEPTORS - monitor blood pH, O2, CO2, glucose levels. •Send information to brainstem that regulates heart rate, vascoconstriction/dilation, and respiratory rate. 1. Carotid sinuses - located in the internal carotid artery. Detects changes in BP. 2. Carotid bodies - located in external carotid artery. Detect changes in O2, CO2, and pH and alter resp. rate. 3. Aortic bodies - located in aortic arch. Chemoreceptors similar to carotid bodies.

Circulatory system

•Blood: liquid connective tissue. •Blood vessels: carry blood from heart, to lungs, to every part of our body and back again. •Heart: contraction generates the force to push blood through the vessels.

Located in center of the thoracic cavity (mediastinum) between the two lungs:

•Broad, superior portion is the BASE •Narrower inferior portion is the APEX •Heart is angled to the left so that about 2/3 of the heart is to the left of the mid-saggital plane (despite what every cartoon would have you think).

Cardiac muscle metabolism

•Cardiac muscle cells rely almost exclusively on AEROBIC RESPIRATION to generate ATP needed for contraction. -Lots of myoglobin. -Lots of large mitochondria. -Lots of stored glycogen. •Makes heart very resistant to fatigue, BUT very vulnerable when O2 is not available (myocardial infarction).

Capillary beds

•Complex network of capillaries that surround tissues of the body. •Exchange of gasses, nutrients, hormones, waste products occurs here. •Every cell in the body is very close to a capillary. •Essentially link between arterial and venous systems.

Hemopoietic Tissues

•During development, formed elements are produced in a variety of tissues. -Bone marrow, liver, spleen, thymus. •After birth, most formed elements are produced by red marrow. -Skull, ribs, pelvis, head of femur, sternum. -All 7 types of formed elements are produced here. -Red marrow is considered myeloid tissue. -Blood production here is known as myeloid hemopoiesis. •However, some lymphocytes are produced or travel to lymphoid tissues (thymus, spleen, lymph nodes, tonsils) where final maturation occurs. -Known as lymphoid hemopoieses. -T-lymphocytes (T-cells). •Myeloid and lymphoid tissues both contain very important stem cells known as pluripotent stem cells. -Pluripotent means they can differentiate or mature into several different cell type. -Pluripotent stem cells give rise to all formed elements.

Pressure gradients

•Generally, pressure gradients cause fluids to flow. -Blood from pulmonary or systemic circuits → atria, or atria→ ventricles, or ventricles → great vessels. •However, AV and semilunar valves prevent this flow even though there is a gradient!!! -Positive pressure in RV and LV force the AV valves to close (no flow back into atria). -Positive pressure in pulmonary trunk and aorta force semilunar valves closed (no back flow into ventricles).

Blood flow and pressure

•In order to sustain life, the circulatory system needs to exchange O2, nutrients, and waste at a pace based on the that tissue's metabolic rate. •Blood supply to a tissue can be expressed as FLOW or PERFUSION. -Flow is defined as the volume of blood flowing into a tissue per minute (mL / min). -Perfusion relates flow of blood to the mass of a tissue or organ (mL / min/ g).

Ventricular contraction

•In reality, the entire ventricular myocardium doesn't contract at EXACTLY the same time. •Path of signal along bundle branches and purkinje fibers cause apex to contract first and the contraction spreads upward (superiorly). •This pattern of contraction helps "push" blood up and out through pulmonary or aortic valves. -Ventricles sort of wring themselves out to ensure adequate ejection of blood.

Lung structure

•Inferior is BASE, superior is APEX. •Surfaces : -Costal surface: anterior, lateral, posterior (faces the rib cage). -Mediastinal surface - medial surface. -Diaphragmatic surface: portion of the base that rests on the diaphragm. •There is a large impression on the left lung where the heart projects laterally - CARDIAC IMPRESSION.

Arteries

•Known as RESISTANCE VESSELS because they resist high pressure of blood leaving the heart -Also due to the fact that constriction of arteries increases resistance in the circulatory system → increases blood pressure. •Arteries are broken down into 3 categories loosely based on size. 1. Conducting arteries: •Largest arteries (aorta, common iliac, subclavian). •Contain a great deal of elastic tissue in tunica media. •Expand during systole and contract during diastole. •Expansion prevents high pressure from reaching smaller arteries. •Contraction ensures blood pressure remains high enough in between heartbeats (WINDKESSEL EFFECT). 2. Distributing arteries: •Smaller arteries that branch off of conducting arteries. •More smooth muscle than elastic tissue in tunica media. •Femoral, brachial, renal arteries are distributing arteries. •Named for their role in distributing blood to a given organ. 3. Resistance arteries: •Smallest arteries that branch off distributing arteries. •Majority of tunica media is smooth muscle. •Usually not named, smallest resistance arteries are ARTERIOLES. •Critically important for regulating the flow of blood to a tissue/organ (a.k.a., perfusion).

Leukocytes (WBCs)

•Least abundant of the formed elements in blood. -However, #'s are actually higher since many leukocytes exit bloodstream and enter tissues. •Unlike RBCs, WBCs possess nuclei, other organelles -More complex functions than RBCs.

Erythropoiesis

•Like all formed elements, RBCs develop from pluripotent stem cells in bone marrow. •The hormone erythropoietin (EPO) stimulates maturation of RBCs -Produced by kidney cells in response to blood loss or low O2 levels in the bloodstream (hypoxemia). -An old-fashioned performance enhancing drug for cyclists, runners, swimmers.

WBC development

•Like all formed elements, WBCs originate from pluripotent stem cells. -Originate in myeloid tissues, but some (T-lymphocytes) travel to and mature in lymphoid tissues (thymus, lymph nodes, tonsils, etc). •Maturation of specific WBCs is triggered by a variety of hormones, biological agents, and environmental agents. -Allows proliferation of specific WBCs in response to need. -Allergens, bacteria/viruses, inflammatory cytokines trigger maturation of specific WBCs.

Pleura

•Like the heart, the lungs reside in the thoracic cavity and are surrounded by two layers of serous membranes. •VISCERAL PLEURA - lies directly on top of the lung. •PARIETAL PLEURA - lines part of the thoracic cavity, mediastinum, and diaphragm. •The PLEURAL CAVITY is space between the pleurae filled with pleural fluid that has three functions. 1. Reduces friction during ventilation. 2. Creates pressure gradient. 3. Compartmentalization of organs.

Conducting Division

•Main function is to move air from outside → inside → back outside. •Several organs also play other roles and contribute to normal function of respiratory system. •Nasal cavity - -Conditions the air as it enters the body. -Nasal conchae create turbulence in air. -Nasal cavity lined by MUCOSAL MEMBRANE. •GOBLET CELLS that secrete mucous, pseudostratified ciliated cells that "sweep" material back so that it can be swallowed. -Air is warmed and humidified •ERECTILE TISSUE in inferior conchae fills with warm blood (common site of nosebleed). -Dust, allergens, other particles get trapped in nasal hairs VIBRISSAE and in mucous that lines the nasal cavity. •OLFACTORY MUCOSA - patch of cells located mostly in superior portion of nasal cavity. •Contains nerve fibers (C.N. I) that pass through cribiform plate.

Capillaries

•Microscopic blood vessels consisting of only an endothelium and basement membrane. •All are relatively porous to allow exchange of products between blood and tissues. 3 main types: 1. Continuous capillaries - most common type of capillary. Contain small clefts between endothelial cells - allow glucose, gasses, small molecules to move into tissue. 2. Fenestrated capillaries - found in organs that need to filter or exchange large quantities of materials (kidney, endocrine glands, intestines). Endothelial cells contain many FILTRATION PORES. 3. Sinusoids - found in organs such as liver, spleen, bone marrow where entire cells and large quantities of proteins are able to pass between endothelial cells. Actually have more open space than endothelial cells.

Main function of respiration is to replenish O2 and expel CO2

•Need O2 for aerobic respiration. •Need to eliminate CO2 waste. •CO2 + H2O → H2CO3 → HCO3- + H+→ acid build up in blood and tissues. •Additional, important functions: -Need to move air for vocalization (speech, laugh, cry, etc...), sense of smell -Respiratory pump aids blood flow back to heart Breath holding - allows us to survive underwater briefly, aids in urination, defacation, childbirth. -Blood pressure regulation via actions of ACE.

Life cycle of WBCs

•Once released into bloodstream, most WBCs rapidly enter tissues to carry out their assigned jobs (within hours). •Most WBCs only live for a few days (neutrophils, eosinophils, basophils), but some can live for years (macrophages) or decades (some lymphocytes).

Influence of ANS on heart rate: Heart Rate Inhibition

•Parasympathetic nerve fibers (via VAGUS nerve) travel to SA and AV nodes. •Nerve fibers release acetylcholine(ACh). -ACh binds to ligand-gated K+ channels causing K+ to flow OUT of S.A. node cells making them HYPERPOLRIZED and very difficult to depolarize. -Slows down depolarization of node cells → slows HR. •Vagus nerve is always affecting HR. -Called VAGAL TONE - reduces HR to normal 75 beats/min (SA node normally fires at rate of about 100 beats/min). -VASOVAGAL SYNCOPE - fainting due to overactivation of vagus nerve.

Blood Vessel Resistance

•Resistance to flow creates pressure within vessels. -Resistance INCREASES blood pressure. •Resistance is influenced by: 1. Blood viscosity - thicker blood flows less easily and is under greater pressure. •Largely affected by RBC# and protein content. 2. Vessel length - blood encounters more friction the farther it travels in a vessel causing a decrease in blood flow → decrease in pressure. 3. Vessel radius - probably the most important and variable factor affecting resistance in a vessel. •Blood flowing through a vessel demonstrates LAMINAR FLOW - essentially flowing in "sheets". -Blood near the walls flows slower due to friction. -Blood in center flows faster. •As a vessel constricts, more blood flows closer to the walls → more friction → more resistance → greater pressure.

Balanced ventricular output cont.

•Similar situation develops if LV output exceeds RV output. •LV is ejecting more blood into the systemic circuit than the RV is sending to the lungs. •Pressure builds up in systemic circuit → systemic edema. -Swelling of legs, feet, and hands can be indicative of heart failure. •Both situations can be caused by damage to the ventricles after a heart attack. -A damaged ventricle cannot pump as much blood. -If one ventricle fails, eventually the other fails too.

Bronchial Tree

•Trachea branches at a point known as the CARINA to form a right and left PRIMARY BRONCHUS. •After 2-3 cm the primary bronchi enter the lung tissue and branch into successively smaller SECONDARY and TERTIARY bronchi. •Distal to the bronchi are the BRONCHIOLES. •Each bronchiole branches into TERMINAL BRONCHIOLES - the end of the conducting system.

Regulation of BP and Blood Flow cont.

•Vasoconstriction/dilation can be controlled in 3 ways: 1. Local control - a form of autoregulation where the blood vessel tissues control diameter üAccumulation of waste products, release of NO (nitric oxide), and prostacyclin from endothelial cells can trigger relaxation of smooth muscle. -As these products get washed away, the vessel constricts again. 2. Neural control - control of vessel diameter by ANS. -Cardiovascular centers in medulla oblongata process information received by baroreceptors and chemoreceptors. -Neural control of vessel diameter is primarily controlled by the SYMPATHETIC division of ANS. -More stimulation of smooth muscle by sympathetic fibers causes constriction, less stimulation causes relaxation. 3. Hormonal/chemical control - a variety of hormones produced by the brain, liver, adrenal glands that alter blood vessel radius and/or fluid balance in the blood. •Angiotensin II - released into bloodstream by liver as angiotensinogen. -Gets converted to Ang II by ANGIOTENSIN CONVERTING ENZYME (ACE). -Ang II is a potent vasoconstrictor. -ACE inhibitors are potent drugs to treat hypertension. •Atrial naturetic peptide - promotes excretion of Na+ → H2O loss→ decrease in blood volume→ decrease in BP. -Also acts as a mild vasodilator. •Nitric Oxide (NO) - a gaseous signaling molecule produced by vascular endothelial cells. -Triggers relaxation of smooth muscle in blood vessels → vasodilation. •Antidiuretic hormone (ADH) - promotes H2O retention and also is a vasoconstrictor. •Epinephrine/norepinephrine - released into bloodstream by adrenal glands and also is the neurotransmitter released by sympathetic nerve fibers. -Causes smooth muscle contraction → vasoconstriction → increase in BP. •Aldosterone - hormone released by adrenal gland that promotes Na+ retention. -Receptor for aldosterone is called the MINERALOCORTICOID RECEPTOR. -The stress hormone CORTISOL can also bind that same receptor - explains increase in BP when you are under stress!!!

Regulation of BP and Blood Flow

•Vasodilation/vasoconstriction have a huge impact on resistance and flow. -Resistance and flow is proportional to the 4th power of the radius (r4) of a vessel. -So very small changes in diameter lead to big changes in resistance and flow. -For example, a doubling in vessel diameter results in a 16-fold increase in flow (i.e., from 1mm to 2mm or 2mm to 4mm). •Ultimately, blood pressure is dependent on resistance (increase in resistance causes increase in BP). •But, blood FLOW is dependent on both pressure and resistance üAt a given pressure, flow can be altered by changing resistance (and vice versa).

Several INTRINSIC muscles and ligaments allow opening/closing of glottis (opening of larynx) as well as movement of vocal cords

•Vestibular fold controls opening of glottis - prevents choking. •Vocal fold - fold of tissue overlying the vocal ligaments. -Inferior to vestibular fold. -Vibrate as air moves over them. -Varying tension on vocal cords allow us to create various "rough" sounds.