Test One Definitions and Concepts Normal varies because all people are different.

e different. Blood glucose, [urine], ADH levels (salt/alcohol intake), location Disease: life beyond normal; homeostasis is threatened or lost Disorder: leads to a restricted life or a loss of life Etiology: causes or reasons for a problem Infection, nutrition, personal habits Pathogenesis: development or evolution of disease Subclinical stage: etiology and pathogenesis exist, but not enough to affect living state Weak heart Clinical stage: individual is aware of problem or symptoms, then signs appear Symptoms: subjective feelings of the patient; cannot physically be measured Signs: things you can physically measure or see Throw up, fever Sequel (sequellae): long-term outcomes or results of a disease or disorder Deformations, limited organ function (leaky heart valve) Complications: new and separate process caused by changes due to the first entity Viral infection in lungs mucous that leads to bacterial pneumonia Lesion: demonstrable structured change Break with bone through skin, low dopamine levels, dead heart tissue

Cellular and Tissue Adaptation Hypertrophy: increased size of cells and organelles without dividing; NOT swelling Hyperplasia: increased number of cells

Degenerative changes in injured cells Response to stress Reversible The plasma membrane is damaged (stretches and leaks) & permeability to sodium increases or there is a decrease in Na+/K+ transport system, which leads to a lack of oxygen delivery. [Na+] in the cell increases; therefore, [ion] in the cell increase & osmosis occurs (H2O diffuses into the cell). The cells vacuoles fill with H2O, the cell swells, and the cell may rupture. Hydropic change: collection of H2O in cells You can see clear vacuoles. Cells will leak certain things when damaged, like creatine phosphokinase (CPK) or glutamic oxalocetic traminase (GOT), usually in the heart, kidneys, and brain tissues. Hyaline degeneration: collection of large amounts of proteins in cells Homogenous, glassy, pinkish tissue appearance

 Fatty change: collection of large amounts of fat in vacuoles that do not normally store fat Foamy appearance (small, clear spheres) Cells enlarge, so the organs of the body also enlarge (possibly 2-3X bigger) Greasy looking and feeling o Hypoxia (low O2 level in cells) decrease in fatty acid oxidation; fat collects because it cannot metabolize in the Krebs cycle. o Alcoholism increases lipid deposits in the liver. o Lipid storage diseases: Tay-Sachs Neiman-Pick Gauchers Atrophy: decrease in cell size resulting from damage or a lack of use Contents of lysosomes are released into portions of the cell, destroying part of the cell but not all of it o Lipofusion: brown atrophy, massive atrophy, aging pigment Color remains when cells break down; caused by an abundance of atrophy Cell death: lysosomes are released into cell and it digests itself Necrosis: biology after cell death 1. Liquifactive Necrosis soup; cell liquefies, then ruptures Surrounding cells are also destroyed. Often found in brain tissue (hole filled with fluid) 2. Coagulative Necrosis Firm substance; outline remains, but proteins are denatured Characteristic ischemic flow (inadequate blood flow) Cell death in non-brain tissue (kidneys and heart) 3. Caseous Necrosis Cottage cheese-like Similar to coagulative necrosis, but cells break down and no form is left Mainly found in TB patients Other names for necrosis: Gangrene: any area of black, smelly tissue Wet gangrene: internal necrosis and putrification caused by microorganism; turns black due to the oxidation of hemoglobin and myoglobin o Cause: Clostridium micro infection (Gas Gangrene) Dry gangrene: ischemic necrosis of the extremities; form of coagulative necrosis; black, dry, and shriveled appearance o Causes: Occlusive vascular disease (blockage of blood vessels) Atherosclerosis (plaque build-up, usually in diabetics) Hypothermia (severe vasoconstriction of blood vessels, frost bite) 2

Somatic death Body death; enough cells die that the organism itself dies Current definition of death: no brain waves Following death: Rigor mortis: 6-8 hours after death; muscles are locked into position because no more ATP is being made o ATP is needed to unbound cross bridge, and without it muscles are stiff. o After 16-20 hours after death, muscle cells deteriorate causing relaxation Algor mortis: cooling of body after death; 1 to 1.5 per hour, depending on the environment Livor mortis: lividity after death (liquids sink to the bottom of the body, resulting in a light color on top and a dark/purple color on bottom); tells us if the body has been moved Genetic Disorders Note: 4% of all live births have some sort of genetic deviation. 25%-40% of all spontaneous abortions have identifiable chromosomal aberrations. Genetic diseases have a familial history that is not necessarily congenital. Congenital: disorders that a person is born with Congenital syphilis Some forms of diabetes are genetic, but not congenital. 1. Polygenic: combination of many genes plus environmental factors involved; vary depending on the number of genes involved and the amount of environmental factor Diabetes mellitus- change based on genes and physical activity Hypertension Schizophrenia Bipolar disorder (manic depression) Rheumatoid Arthritis Gout (hyperuricemia): high amounts of uric acid precipitate into crystals, which leads to the breakdown and inflammation of joints (sandy joints) Tophi- inflammatory spaces caused by the crystals that starts in big toe 2. Single Mutant Genes of Large Effect: one gene involved; Mendelian Disorders; 80%-85% are familial and others are new mutations; 46 chromosomes, 2 are sex chromosomes Autosomes: 44 chromosomes that are not sex chromosomes Gamete: egg/ovum or sperm Zygote: fertilized ovum; full number of genes Allele: trait a gene expresses; one of several possibilities Homozygous: both alleles are the same Heterozygous: 2 different alleles Dominant allele: always expressed Recessive allele: only expressed if two recessive alleles are present (homozygous); often do not affect the phenotype (heterozygous) Phenotype: physical appearance 3

 Genotype: genetic makeup Autosomal Dominant Disorders Dd X dd = 50% chance of having disorder Dd Dd dd dd DD X dd = 100% chance of having disorder Dd Dd Dd Dd Examples: Marfans Syndrome o leads to the production of a defective collagen (protein fibers in connective tissue) and collagen is too elastic, so there is a hyper-extensibility of joints o slender, long bones and limbs (legs, arms, fingers); lens of eye becomes dislocated, leading to visual problems; weak blood vessels, which can lead to aneurysm; weak, floppy mitral and aortic valves o Abraham Lincoln Autosomal Recessive Disorders Dd x Dd = 25% chance of having disorder DD Dd Dd dd Dd x dd = 50% chance of having disorder Dd Dd dd dd Sometimes heterozygous people will show some characteristics of the disorder (ex. PKU), but most do not show the disorder at all. Often the disorder alters enzymes- d makes an incomplete enzyme, and D makes enough to compensate. Over 100 disorders: Cystic Fibrosis o Deficient exocrine secretion (glands with ducts to elsewhere) o Abnormal sweat (increased Na+) and mucous (thick and gooey) builds up and blocks ducts; pancreatic duct can be blocked, which causes ineffective digestion and malnutrition; mucous blocks bronchi, which leads to severe respiratory problems (pneumonia and infection) o Treatment: mucous plugs must be removed/coughed up o 25% dead by 20 years old

 Phenylketonuria (PKU) o Phenylalanine amino acid tyrosine thyroxine, melanin, and dopamine o Inability to produce phenylalanine hydroxylase, so tyrosine becomes an essential amino acid (must be obtained in the diet) o No treatment: phenylalanine buildup in body demyelization retardation; less than 4% have an IQ > 50-60 o Fair skin and blonde hair- lack of tyrosine leads to a lack of melanin o Treatment: restricted diet Sex-linked (X-linked) Disorders Mutant gene or disorder is carried on X chromosome (Y chromosome is little, so it carries only the most important information); Recessive allele on X chromosome Mainly in male children (mother to son); in females, dominant X chromosome wins Lethal; men usually die before reproductive age * next to X represents a recessive allele on the X chromosome X*X x XY = 25% chance of children having disorder; 50% chance males will have the disorder; 50% chance females will carry the disorder X*X X*Y XX XY Hemophilia A: clotting disorder; cannot produce factor VIII; blocks one of two pathways for clotting blood, making small cuts dangerous 3. Aberrations in Karyotype (Chromosomes) Abnormal number or shape of chromosomes Gamete will have an extra or missing allele because of nondysjunction (all cells) Mosaic: some cells nondysjunction during development after fertilization and other cells are normal Most extra chromosomes are fatal; there are no autosomal monosomes (missing chromosomes) Example: Trisomy 21, Downs Syndrome o 3 chromosomes on the 21st set o Frequency depends on age of mother <29: 1/2000 >45: 1/50 Ovaries can be affected by the environment & age o Flat face; epicanthic folds on eyelids; single horizontal palmar crease (Simeon crease); IQ 25-50 o 5% have nondysjunction during development (mosaic); some cells in body have 3 chromosomes and some only have 2 Translocation: movement of one chromosomes genes to another chromosome Klinefelters Syndrome: XXY (extra sex chromosome) 5

o aka testicular dysgenesis because testis are not fully developed o most likely sterile; low testosterone levels o 1/500 live male births Turners Syndrome: XO (missing sex chromosome) o female o only known monosomy (single sex chromosome) o shorter than average, shield-like chest; widely spaced nipples, webbing of neck, digits, and axilla (armpit); secondary sex characteristics decreased (pubic hair, genitalia); amenorrhea (no menstruation) Deletion: chromosome broken; loss of DNA Cri du chat: deletion in part of chromosome 5 o Microcephaly (small head/brain), epicanthic folds on eyes, meowing cry; some retardation Neoplasia New cell growth or division; uncoordinated growth in excess of normal growth (tumor); behaves like a parasite Reversible cell growth Not neoplasia Regeneration: increased division of cells to replace tissue after a wound Hyperplasia: increased division of cells (cell #) Might be physiological (growth of breasts) Might be pathological (ovarian tumor that produces excess estrogen, which increases size of endometrium, leading to heavy/painful periods) Metaplasia: adaptive replacement of one type of cell with a better, new type of cell Ex. Irritated cervix changes from columnar to squamous cells that are more durable. Dysplasia: cells lose uniformity and become pleomorphic (lose size, shape, and appearance) Most disorderly non-neoplastic growth Usually epithelia exposed to chronic irritation or inflammation (bronchi of heavy smokers); can transform to cancer Non-reversible Cell Growth Neoplasia Oncology: the study of tumors Benign neoplasm: non-cancerous, localized tumor; more controlled growth than cancer; can be dangerous in the brain by crushing other areas of the brain and causing a loss of function; usually ends with oma (means innocent) Relatively well-differentiated Relatively low number of mitotic figures (slow cell division) Normal mitosis- forms capsule around itself and stays put

1. Fibroma: benign tumor of fibrous connective tissue 2. Chondroma: benign tumor of cartilage 3. Adenoma: benign tumor of glandular tissue Malignant neoplasm: cancer; hypocrisies in ancient Greece coined the phrase carcinoma, meaning crabs; cancer spreads in unusual ways; often ends with sarcoma Not well differentiated Anaplastic: cells are undifferentiated Pleomorphic: neighboring cells look different; more primitive Large nuclei (nucleus: cytoplasm=1:1) Atypical mitosis No capsule Cells are not cohesive/stable- leave one area to form tumor(s) elsewhere Sarcoma: arise from connective tissue and named based on where they come from o Fibrosarcoma: fibrous CT o Osteosarcoma: bone o Chondrosarcoma: cartilage Carcinoma: arise from epithelia o Squamous cell carcinoma: type of skin cancer o Adenocarcinoma: adrenal gland o Melanoma: most dangerous skin cancer; not named correctly- should be melanocarcinoma o Seminoma: testicular cancer Metastasis: tumor cells are all over an area of the body o Pap smear to look for cancer (can be done anywhere) o Logical pathways: Blood vessels can transport to the next set of capillaries o Extravasate- leave the blood vessels o Portal- connects organ to organ o Primary tumor in gut; secondary tumor in liver o Primary tumor in limb; secondary tumor in lung Transport through lymphatic system to nodes o Primary tumor in breast; secondary tumor in axilla Radical surgery (entire breast & lymph nodes vs. lumpectomy) o Primary tumor in mouth; secondary tumor in neck (cervical nodes) o Lymph nodes thoracic duct left subclavian heart Seed through a body cavity (travel on liquid in cavity) o Brain subarachnoid space in meninges body o Lung pleural cavity body o Spinal cord nervous system 7

Transformation: process of cells becoming malignant; not well known o Loss of control of cell division o Loss of contact inhibition (stop division when in contact with other cells); cancer cells keep dividing o Desmosomes lost (connections between cells) o Metastasis occurs o Cells become anaplastic (primitive) Carcinogens: agents that induce transformation (biological, chemical, physical) o Some dyes (azo and analine), mutagens (nitrosamine), solvents (benzene), used motor oil, ash or soot o Dose-related: chances depend on how much and how often exposed o Lag time: time after exposure before cancer appears (50 days to 20 years) o Oncogenic virus: virus that can cause cancer (Herpes, Epstein Barr) o Radiation: X-rays, UV light; causes mutation, breaking DNA Roentger (X-rays), Marie Curie (Uranium)

Immune System Inflammation and repair Inflammation: reaction to tissue that is in some way injured in capillaries 5 cardinal (primary) signals: o Redness: due to arterial dilation and hyperemia (increased blood flow); vasodilation due to histamine and serotonin release o Heat: hyperemia brings heat to skin o Pain: mediators released from mast cells (histamines, prostaglandins) bind pain receptors; pressure from swelling o Swelling: movements of fluids and cells into the region of inflammation o Altered function: limited use of inflamed area due to pain Capillary dynamics/fluid aspects o Constriction of arterioles Increases BP in arteriole and decreases BP in capillaries o Loss of blood Interstitial fluids replace loss of plasma without proteins No osmosis- increase in flow out of capillaries o Edema: more fluid is escaping capillaries than is returning; causes swelling (high BP) o Increased permeability of capillary to proteins & increased flow out of capillary (decrease in osmotic pressure, ) o If vasodilation occurs, arteriole BP decreases and capillary BP increases. o Blood plasma is the source for ECF. o Bulk flow: H2O and dissolved substances flow outside of the capillaries o Osmosis: H2O toward higher [solute]

o Exudate: fluid or cells that have leaked from blood vessels that contain protein; not related to BP o Transudate: fluid or cells that have leaked from blood vessels that do not contain protein; does not happen in inflammation o Albumin: primary protein; egg whites

Inflammatory Mediators o Increase in capillary BP o Proteins leak out of capillary (destroys gradient) Amines: histamine and serotonin; short-term; early inflammation Leukotrienes: longer term; vasoactive effects Prostaglandins: can cause pain; aspirin blocks this Mast cells: when bound to IgE, they release eosinophil chemotaxic factor of anaphylaxis o Eosinophils collect wherever IgE is located. Basophil: WBCs that carry mediators; like mast cells in the blood Degranulation: Release of contents into the surrounding cytoplasm Kinins: inflammatory mediator o Bradykinin- complex release based on enzyme cascade Cellular Aspects of Inflammation o Blood becomes more viscous and becomes thicker o WBCs stick to walls and flatten, then move to margins of vessel (margination/pavementing) o WBCs then migrate from blood vessel into cytoplasm (emigration by diapedesis, similar to amoeboid activity) o WBCs go straight to the sight of damage by chemotaxis Chemotaxis: organized chemical trail toward site of inflammation along chemical gradient Blood Cells and Function 1. Agranulocytes: monocytes and lymphocytes o Monocyte: immature macrophage Macrophage: collects at site of inflammation 3-7 days after damage; responds to opsonins and lymphokines that bind to macrophage making it a hyperactive and aggressive angry macrophage; active in chronic inflammation; most active phagocytes o Lymphocyte: B&T cells; travel to thymus or bone marrow and mature there 2. Granulocytes: neutrophils, eosinophils, and basophils; contain enzyme granules Neutrophil: (PMN or polymorphonuclear neutrophil, polys); looks like it contains three nuclei, but only has one; first cells to appear to inflammatory site; 6 hour half-life (do not stay long); phagocytic (increased eating if it has been opsoninized) o Opsonin: flag that attracts foreign cells, usually IgG o Complement system: destroys pathogens by activating neutrophils (and other WBCs) 10

o Eosinophil: collect at sites of allergic reaction and parasitic worm infections o IgE bound mast cells attract eosinophils o IgG binds to worm and eosinophils attach to break down its surface o Basophil: behaves like a mast cell

Patterns of Inflammation Based on the type of fluid that collects o Serous exudate: thin, clear, watery fluid with few leukocytes that collects early in inflammation; contains proteins (ex. liquid inside blister) o Fibrinous exudate: thin, clear fluid with fibrinogen, which helps blood clot Activates, forms fibrin, and begins hardening in body cavity. This causes painful friction rub on serous surfaces (peritoneum, pleura, and pericardium) o Cellular exudate: purulent; fluid has cells (neutrophils) in it Large collection called pus (PMNs rupture, releasing lysosomes that digest surrounding cells) Usually bacterial infection or necrosis o Suppurative exudate: collection of pus; forms an abscess o Abscess: pus-filled hole in tissue

Wound Healing and Repair Minor Damage/No Infection Regeneration: ability of tissue to proliferate the remaining cells Resolution: restoration of the original structure and physiologic function Major Damage/Infection Incapable of resolution Repair: replacement of destroyed tissue with scar tissue Fill in the wound. Cover or seal the wound. Shrink the wound. Collagen: material that scar tissue is made of; fills in the lesion and restores tensile strength, but cannot carry out the physiologic function of destroyed tissue Both regeneration and repair begin during inflammation with phagocytosis of particulate matter in the inflammatory exudate. Fibrin from dissolved clots, microorganisms, and dead tissue cells Debridement: clean-up of lesions; involves dissolution of fibrin clots by fibrinolytic enzymes After debridement: Exudate, toxic products, and particulate matter are drained away. Vascular dilation and permeability are reversed, preparing the lesion for regeneration or repair. 11

Types of Wound Healing Primary intention: wounds that heal under conditions of minimal tissue loss (ex. clean incision) These wounds are the easiest to heal because: o sealing has already been facilitated by minimal tissue loss o apposition (joining) of the wound edges o very little epithelialization (sealing and shrinkage) needed Secondary intention: open wound Epithelialization, scar formation, and contraction take longer.

Phases of Wound Healing Reconstruction phase Begins 3 to 4 days after the initial injury and continues as long as 2 weeks Aka proliferative, fibroblastic, or connective tissue phase 1. Seal off wound o A blood clot is formed containing fibrin and trapped cells (RBCs and WBCs). o The cross-linked mesh of fibrin is created by activation of the coagulation cascade. o One fibrin mesh traps platelets, which further seals damaged vessels by forming a platelet plug. o Most wounds are completely sealed hours after they have been closed. o Sealing creates a barrier against bacterial invasion. Tissue formation o Plasma fibrinolytic system or the release of lysosomal enzymes from dead neutrophils digests the clot. o The fibrin clot is dissolved and replaced by normal tissue or scar tissue. o Macrophages enter and phagocytize debris and dead cells. Regeneration/repair o Minor damage: regeneration of destroyed cells (process ends here) o Major damage: replacement with scar tissue (process continues) Granulation tissue grows inward from surrounding healthy connective tissue. Granulation tissue is filled with new capillaries that give it a red, granular appearance surrounded by fibroblasts and macrophages. Collagen synthesis o Fibroblast proliferation: Fibroblast-activating factor causes fibroblasts (CT cells) to enter the lesion and secrete procollagen (collagen precursor). This process happens about 6 days after the fibroblasts have entered the lesion. o Epithelialization: the process by which epithelial cells grow into the wound from surrounding healthy tissue to protect the healing wound Macrophages secrete a factor that attracts epithelial cells, and they migrate under the clot or scab using proteolytic enzymes (digest 12

2.

3.

4. 5. 6.

proteins) to sever the connection between the clot and the wound surface. The migrating epithelial cells contact similar cells from all sides of the wound. After the wound is sealed, migration and proliferation cease. 7. Remodeling o Scar tissue is dissolved and reformed along the mechanical stress zones. 8. Contraction o Inward movement of the wound edge approximately .5 mm/day o Noticeable 6 to 12 days after the injury Maturation phase Begins several weeks after injury and is normally complete within 2 years Aka differentiation, remodeling, or plateau phase Continuation of reconstructive phase Scar tissue is remodeled Capillaries disappear, leaving an avascular scar Within 2 to 3 weeks from beginning of maturation phase, the scar tissue has gained about 2/3 of its eventual maximum strength. Compensatory hyperplasia: the ability of complete mitotic regeneration Epithelia, liver, or bone marrow only Dysfunctional wound healing Insufficient repair, excessive repair, or infection Dysfunction during inflammatory response: Hemorrhage- bleeding is not stopped during acute inflammation o A clot increases the amount of space that granulation tissue has to fill and serves as a mechanical barrier to oxygen diffusion. It also prolongs the inflammatory process because the cells must be cleared before repair. o Accumulated blood is a perfect culture medium for bacteria promoting infection. It prolongs inflammation by increasing exudate and pus formation. Excess amounts of fibrin o Fibrous abhesion: unabsorbed fibrin that can stick to organs and bind them together o Hypovolemia: decreased blood volume, which inhibits inflammation Dysfunction during reconstructive phase: Impaired collagen synthesis o Most factors that affect the ability to make collagen are related to nutrition. Ex. Scurvy leads to fibroblasts that do not release collagen. Ex. Ehlers-Danlos Syndrome: defect in collagen synthesis that prevents the formation of normal connective tissue, causing thin and fragile skin. 13

Overproduction of collagen o Causes surface over-healing o Keloid: raised scar that extends beyond the original boundaries of the wound o Hypertrophic scar: a raised scar that remains within the original boundaries of the wound; tends to regress over time Impaired epithelialization o Epithelialization suppressed by anti-inflammatory steroids, hypoxemia, ionizing radiation, and zinc deficiencies Wound incorporated into clot will increase epithelialization time Wound disruption o Dehiscence: wound pulling apart at suture line Usually 5 to 12 days after injury 50% associated with wound sepsis Impaired contraction o Contraction is necessary for healing. o Contraction is mediated by fibroblasts. o Contracture: deformity of wounds, common in burns Proper positioning and physical therapy can overcome contracture. Smooth muscle inhibitors can overcome contracture.

Immunity Antibodies and Immune Response Specific Immunity Lymphocyte: white blood cells that determine the specificity of the immune response to infectious microorganisms and other foreign substances; T and B cells Humoral immunity: Antibody-mediated; antibody (Ab) released from plasma cells (subclass of activated B-cells) o Antibody (Ab): immunoglobulin that binds to antigens (Ag) Antigen specific- contain specific protein capable of binding to Ag Made from B-cells o Antigen (Ag): compound that an Ab can bind to; anything to which you can make an Ab o Immunoglobulin (Ig): four protein chains linked together making a Y shape that recognize and neutralize foreign objects IgG: gamma globulin o Most common group o Small enough to cross the placenta & gives immunity to babies Erythroblastosis Fetalis Note: Rh Factor Rh: Rhesus antigen Rh-positive: Rh antigen present o Rh Ab absent 14

Rh-negative: Rh antigen absent o Rh Ab absent (normally) o Ab is only made if exposed to Rh-positive cells (Ag) Erythroblastosis Fetalis Rh-negative mother and Rh-positive baby Blood from the placenta in after-birth enters mothers body, causing mother to make Rh-positive Ab. During second pregnancy with an Rh-positive baby, the fetus is attacked by mothers Ab. Rhogam: Rh gamma globulin; anti-Rh Ab; Ab destroys any fetal cells & then the Ab is destroyed over time. Mothers immune system is not activated, and she does not make any anti-Rh Ab. It is common for such a small amount of blood to mix that the mother does not make enough antibodies to be fatal to the next Rh-positive fetus. This leads to jaundice.

Type A B AB O

Ag A B A&B -

Ab B A A&B

Blood transfusions If recipient has Ab, then transfusion is fatal. If donor has Ab, then transfusion is not fatal. Antibody to incoming blood = reaction In type 0, Ab is spread thinly. IgE: associated with the anaphylactic system (allergic reactions) o Attach to mast cells and basophils to activate them to release histamines, serotonin, etc. (degranulation) Only works if Ag is also bound o Basic Y shape o Made near body surfaces IgA o Found along mucosal surfaces (any hollowed structure open to the outside of the body) Digestive, urogenital, & respiratory systems o 2 Y structure hooked tail to tail IgM: early and short term protection against bacterial or viral infections o Largest in terms of size o 5 Y structure; snowflake 15

o IgD o o o

IgG Ab comes a week later Not well understood Basic Y shape Theory: activation of B-cells

o Functions of Antibody Agglutinate and precipitate Ag o Bunch together and form a solid Bind to bacteria and become opsonins Initiate complement activation o Enzyme divides a protein in blood making 2 molecules o Pattern continues , forming many molecules, which destroys cell integrity B B1 & B2 C C1 & C2 D D1 & D2 o Anaphylatoxins: mast cell degranulation; stimulates smooth muscle contraction and chemotaxis Cell-mediated Immunity: involves T-cells T-cells divide and send daughter cells to inflammation/infection T-cells destroy infecting body at sight of infection Can be sensitized by contact with Ag o T-cell receptor site available to receive Ag o Pre-existing clone theory: theory that all possible Ag T-cell receptors exist in everyone Upon activation, T-cells rapidly divide & attack infection Some T-cells: o Bind to target cells and release toxic compounds that destroy the cell (cytotoxicity) o Release lymphokines: mediators that stimulate macrophages making them angry o Can recruit new lymphocytes to attack a specific Ag (transfer specific reactivity) o Are involved in chemotaxis Cell-mediated Immunity: Ag is cellular or large Ex. bacteria Humoral Immunity: Ag is small Ex. protein Hypersensitivity: unwanted/inappropriate immune reaction (allergic reaction) 16

Old definitions: o Immediate type: Humoral; involves antibodies o Delayed type: Cell-mediated; involves T-cells Modern definitions: o Type I: involves IgE in individuals who have prior sensitization/exposure to Ag IgE-Ag complex molds with mast cell/basophil, which releases vasoactive mediators Common in epithelia Examples: penicillin and bee allergies Signs and symptoms: o Decreases blood volume and BP leading to anaphylactic shock o Laryngeal edema: voice box constriction/blockage of air pipe respiratory failure o GI cramping, vomiting, and diarrhea o Uriticaria: itching; hives; common in palms and scalp o Angioedema: localized swelling, common in hands, feet, scrotum, and tongue o Any of these signs/symptoms can happen in minutes. Treatment: epinephrine shot (epi pen) o Prevents degranulation of mast cells/basophils o Makes breathing easier by increasing BP and dilating bronchioles o Decreases smooth muscle activity (gut, etc.) o Decreases histamine release from mast cells Atopic diseases: not life threatening; localized allergic responses o Allergic Rhinitis: inflammation of the nose; Hay fever; stuffiness, secretion, and sneezing ; eosinophil collection; might develop blockage of the Eustachian tubes leading to Otitis media Pruritis: itching (nose, throat, and ears) o Otitis media: inflammation of the middle ear; leads to fluid collection causing earaches o Type II: Cytotoxic disorder; cells are attacked and destroyed; tissuespecific; Ag is specific to a certain cell type and makes antibodies against the whole cell (auto-antibodies) IgG or IgM Examples: o Autoimmune Hemolytic Anemia: attack of RBCs by: Compliment- receptor blockage forms nonfunctional tissue, but does not destroy the cell o Goodpastures Syndrome: attack of basement membrane glomerular kidney failure Macrophages T-cells 17

o Graves Disease- thyroid is activated by antibodies, which produce hyperthyroid hormones o Type III: caused by immune complexes; Ab (usually IgG) attack freefloating Ag; collect in one area, increasing inflammation and causing tissue damage Arthus reaction: Large amounts of Ag and Ab simultaneously by injection of Ag into body, which increases Ab-Ag complex, causing massive inflammation and damage o Artificial in animals; can occur naturally in any tissue that collects large amounts of Ab and Ag o Can be a chronic auto-immune disorder due to infection Disorders: o Glomerulonephritis kidney failure o Severe arthritis o Damage to heart valves heart failure o Long-term bacterial infection without treatment Syphilis o Leprosy o Malaria o Lupus (SLE) o Type IV: cell-mediated; no antibody; delayed type hypersensitivity Destruction by T-cells o Contact dermatitis- poison ivy Ab protein on poison ivy is incorporated into cell membrane and cells are seen as foreign, so T-cells attack Rash and pruritis o Transplant rejection Histocompatibility Ags- identify cells as self or non-self Cells have Ag complex not recognized by your body, so they are attacked. Anti-inflammatory drugs (steroids) Immunodeficiency Diseases: improper immune response o Brutons Agammaglobulinemia: body cannot make Ab because of a lack of B-cells; sex-linked genetic disorder (only cell-mediated responses) o DiGeorges Syndrome: lack of or reduced thymus, so little or no T-cells (no cell-mediated responses) o Swiss Agammaglobulinemia: decreased or absent thymus and lymph nodes (decreased Ab and T-cells); generally die before first birthday when moms antibodies disappear (no responses)

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o Wiscott-Aldrich Syndrome: decreased or absent IgM; reduced immune activity against polysaccharide Ag (pneumococcus pneumonia); prone to bacterial pneumonia o AIDS (acquired immunodeficiency syndrome): final stage of HIV disease, which causes severe damage to the immune system Theory: chimpanzees in Africa in the 1950s, who do not die from HIV Retrovirus (RNA) that can integrate into cells DNA Primarily attacks T-helper cells; lymphocytes cannot be activated Late stage virus attacks the nervous system, causing dementia Some people are immune because they only have one receptor and HIV must have 2 receptors to attach to cells. Nervous System

Synapse: junction between 2 neurons Neurotransmitter (ACH) binds to post-synaptic neuron, which opens Na+ channel Na+ fluids into post-synaptic neuron depolarizing it and causing an action potential (AP) to occur Acetylcholine (ACH) is released, along with ACH-esterase enzyme from the postsynaptic neuron ACH-esterase eats the ACH or it returns to the pre-synaptic neuron o Some are inhibitory: stop/slow flow to the next neuron o Some are excitatory: increase the flow to the next neuron Diseases Tetanus: inhibitory synapses are locked, but excitatory synapses still work so there is constant stimulus; Clostridium tetani bacterium is the toxin that blocks the receptors Botulism: Clostridium botulinum toxin prevent ACH release at neuromuscular junctions 19

o Nerve gas destroys the esterase, which leads to a constant stimulus; antidote is atropine (leads to paralysis) Neuromuscular junction:

Simple Nervous System Structure

Brain Stem: Pons: motor control and sensory analysis Medulla: autonomic vital body functions (blood pressure, breathing, heartbeat) Midbrain: vision, hearing, eye movement, and body movement Cerebellum: regulation and coordination of movement, balance, and posture Diencephalon: contains the thalamus and hypothalamus Thalamus: sensory and motor functions Hypothalamus: homeostasis, emotion, thirst, hunger, circadian rhythms, and control of the autonomic nervous system Cerebrum: main part of the brain; higher brain function Central sulcus/fissure: divides the brain into frontal and parietal lobes Frontal lobe: portion of the brain in front of the central sulcus Parietal lobe: part of the brain behind the central sulcus Occipital lobe: caudal portion of the brain; divided by the parietal-occipital fissure Temporal lobes: thumb portion on the sides of the brain o Red nucleus

Areas that Detect Sensory Input Visual cortex: occipital lobe; vision Auditory area: temporal lobes; hearing Post-central gyrus: primary somatosensory area; behind the central sulcus on the parietal lobe; sensory interpretation 20

Somatosensory association area: behind the post-central gyrus; input from memory and PSA, but no visual input Ex. 2 cubes of the same size and weight; one is a building block and one is an ice cube; differences

Areas that Detect Motor Input Pre-central gyrus: primary motor area; in front of the central sulcus on the frontal lobe; voluntary movement initiation; down in front to remember motor area is precentral Frontal association area: pre-motor cortex; helps coordinate complex motor movements (ex. hand skills) Brocas area: left side of the brain above the temporal lobe; major speaking area Lesions can cause non-purposeful words to be said. (You know what you want to say, but you cannot say it.) Motor apraxia: non-purposeful and non-coordinated movement caused by lesions on the pre-motor cortex Motor aphasia: inability to speak due to lesions on the pre-motor cortex Basal ganglia: motor control center Thalamus, subthalamic nuclei, & red nucleus work with basal ganglia Have synapses in basal ganglia, along with extrapyramidal pathways Extrapyramidal pathways: synapses found in the basal ganglia; do not pass through the pyramid of the medulla on the way out of the brain Lesions can cause Parkinsons Disease Stop here for test #1.

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Test Two Spinal Tracts Group of axons that run up & down the spinal cord Names: 1st part is where the nerve originates. 2nd part is where the nerve ends. Sensory go from the PNS to the brain. Motor go from the brain to the PNS. Spinothalamic tract: spinal cord to thalamus; sensory Rubrispinal: red nucleus to spinal cord; motor Corticospinal: cerebral cortex to spinal cord; motor

Common tracts: Sensory o Spinothalamic: spinal cord to thalamus Lateral: pain and temperature senses Ventral: touch senses o Posterior white column: carries information for touch, pressure, and proprioception (muscle length, muscle pressure, tension, etc.); used to make coordinated movement o Spinocerebellar: proprioception from muscle spindle organs (knee jerk reactions) Spastic, uncontrolled movement without this Allows for coordinated movement (tells stretch, tension, etc.) Motor o Corticospinal: cerebral cortex (primary motor cortex) to spinal cord Lateral and ventral tracts Initiation of voluntary organs Pyramidal pathways (run through pyramids of medulla) o Rubrispinal: red nucleus to spinal cord o Reticulospinal: Reticular formation to spinal cord Group of synapses that extend down the spinal cord NOTE: First Order: crosses over at level of entry Second Order: crosses over in medulla Third Order: thalamus to sensory cortex Road maps Spinothalamic tract: o Lateral: pain and temperature 1st PNS to spinal cord 2nd crosses over spinal cord to brain 22

3rd thalamus to primary somatosensory cortex o Ventral: crude touch Same pathway, but different part of spinal cord Posterior white columns: o Fine touch discrimination (2-point/vibratory) 1st peripheral through spinal cord to medulla o Does not cross over in the spinal cord 2nd medulla cross over to thalamus 3rd thalamus to primary somatosensory cortex o Ex. Cut on left side of spinal cord- lose senses on left side o Cut on left side after medulla- lose senses on right side Pyramidal tracts: o Lateral corticospinal tract 1st primary motor cortex to medulla (through pyramids) 2nd crossover in pyramids through spinal cord to level of exit, then motor neuron to muscle Final common pathway: motor neuron to muscle; does not have to be this tract; can be another one (reflexes) Decussation of pyramids: crossover point in the medulla o Ex. same side of cut in spinal cord; brain lesion opposite side Extrapyramidial pathways: o Synapses occur in these o Does not pass through pyramids of medulla o Subconscious gross movement o Coordinate activity initiated by pyramidal tracts o Red nucleus, basal ganglia, reticular formation, cerebellum o Ex. Reticulospinal & rubrispinal tracts

Brown Sequard Syndrome: cut through the spinal cord half way through and perpendicular in the body Crosses over in medulla All motor and sensory activity below the cut is lost These things will happen: o Pain and temperature is lost opposite from the lesion o Fine touch/vibration is lost on the same side of the lesion o Crude touch is lost on the opposite side form the lesion o Voluntary motor is lost on the same side of the lesion Babinski response: Normally: o Plantar flexion: taking an object from the heel to the toes on the bottom of the foot quickly causes the toes to curl; means pyramidal neurons are normal Negative Babinski response 23

Reflexes

Abnormally: o Dorsi flexion: toes spread out/extend from the body; means there is extensive pyramidal neuron damage Damage to corticospinal tract upward fanning of big toe Positive Babinski response Children under the age of 2 will have a normal Dorsi flexion response.

Deep Tendon Reflex (DTR) Stretch muscle and the SC responds Ex. knee jerk reaction (aka muscle stretch reflex) Continuous loop from the muscle to the SC Anti-gravity: maintains muscle tone motor neurons go to every muscle fiber in the muscle cell except the intrafusal fiber Intrafusal fiber: sensory muscle inside normal muscle motor neurons end in intrafusal fibers SC to intrafusal fiber on gamma efferent neuron (motor neuron), which stretches the intrafusal Stronger AP= stronger reflex Spindle organ: found in intrafusal fiber (attachment of muscle to tendon); very sensitive to stretch; when stretched, sends an impulse to the SC Rounds in SC and returns to muscle on final common pathway (alpha motor neuron) Too much activity by brain kick more & vice versa Look for brain damage Inhibition Areas (-) Basal ganglia Most of the cerebellum Bottom portion of the reticular formation (medulla) Stroke in basal ganglia (- area) o Increases reflex (kick harder) o Inhibition lost o Clonus: extreme reflex excitation Tip-toes to heels, bounce back up

Excitatory Areas (+) Reticular formation (medulla) Portion of the cerebellum Stroke in reticular formation of medulla (+ area) o Decrease reflex o Excitation lost

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Grading System of Reflexes +4 o Very brisk (quick & strong) o Clonus may be present Clonus: loss of inhibitory responses, but excitatory parts are still working (causes a stronger reflex) o Typically associated with upper neuron damage (CNS) +3 o Brisker than average o More reflex than normal +2 o Average/normal +1 o Somewhat diminished o Less reflex than normal 0 o No response Types of Rigidity Note: Arm is relaxed and extended toward the clinician (nurse/doctor). The clinician bends the arm at the elbow toward the patients body.

Pyramidal Pathway Lesions Spasticity of extensors Clasp-Knife Reflex o Initial resistance o Collapse o No resistance o *Regular pocket knife Extrapyramidal Lesions Lead Pipe Rigidity o Resistance throughout o *Lead pipe does not break. It bends with constant resistance. Cog Wheel Rigidity o Resistance o Loss of resistance o Jerk o Repeat o *2 gears of uphill train

Other signs and symptoms (S&S) of Extrapyramidal Lesions Tremor: involuntary tremulous/vibratory movement Rest tremor: constant tremor o Common in Parkinsons Disease 25

Intention tremor: movement tremor o Common in cerebellar lesions or lesions on motor/sensory pathways that travel in and out of the cerebellum o Patient cannot determine the proper location of the object of interest. Overshoot is involved.

Chorea: involuntary movements of face, extremities, or trunk Rapid, purposeless, and jerky movements Typical of lesions to the basal ganglia Athetosis: slow, twisting, sinuous (worm-like) movements, especially of the face or hands; postural issues Seen in Cerebral Palsy & lesions of the globus pallidus (nucleus of the basal ganglia) Dystonia: parts of the body are held in abnormal positions for a period of time, then move rapidly to a different position

Note: Cerebellum coordinates motor activity. In rapid muscular activity (e.g. typing, running, & talking), it makes sure you are where your cortex wants you to be. A lesion can lead to unsmooth motor activity & intention tremors. Lesions to the cerebellum include the following symptoms: Dysmetria: overshoot; unable to determine distance from object(s) Ataxia: uncoordinated movements (e.g. staggering gait/drunk walk) Common in spinal pathway lesions (spinal-cerebellar tracts) Dysarthria: ataxia of the mouth, larynx, & respiratory system; uncoordinated speech Jumbled vocalization & scanning speech Scanning speech: variations in power of speech, as well as usual breaks in words Nystagmus: intention tremor of the eyeball; vibration when you look to the side Hemiballism/Hemiballismus: involuntary violent movements of large body areas (e.g. kick legs); caused by lesions of the sub-thalamic nuclei

Specific Syndromes of the Nervous System Include previous signs and symptoms Parkinsons Disease Paralysis agitans Most common neurological disorder of aging Idiopathic: unknown etiology (aka essential) Antipsychotic drugs can induce Associated with dopamine deficiencies Too much excitatory activity in sub-thalamic nuclei 26

Initial rest tremor of hands Spreads over time to arms, face, and tongue Lead pipe/cog wheel rigidity Substantia nigra regeneration (the black substance below red nucleus) is found in autopsy Brady kinesia: slowness in initiating movements; leads to: Slow, slurred speech and walking Poor balance Festinating gait: lean forward and shuffle feet Akinesia: no extra movement; arms do not swing while walking Hyperactive glabellar reflex: blink reflex; cannot keep eyes open when tapped between the eyes Palmomental reflex: stroke palm of hand with thumb, & chin wrinkles on ipsilateral side Mask-like facies: wide-eyed, unblinking, staring expression Blink only 2-3 times per minute (normal is 12-20 times per minute) Kyphosis: hunched over Monotone speech Micrographia: tiny writing

Multiple Sclerosis Hardening in the NS due to a buildup of connective tissue around the neurons where myelin should/used to be (demyelination) Unknown etiology Cyclic: cycle of active phases and relief/remissions with progressive degeneration Common demyelination in : Pyramidal pathways Posterior white columns Around ventricles of the brain Optic nerve Pons Medulla Acute phases of inflammation and edema Macrophages actively remove myelin Reactive gliosis: rapid increase in the number of glial cells; laying down of fibrous CT (scar tissue) in place of myelin Disrupts transmission of action potentials (slow or none) Symptoms depend on where inflammation takes place Effects depend on pathway involved Could result in: o Paresthesias: sensory input disorder o Visual disorders blurred vision/blindness Blindness in one eye in 40% of patients o Spastic weakness of limbs (tired and heavy) o Hyperactive reflexes + Babinski possible 27

Cerebellum involved ataxia, nystagmus, intention tremors, etc. o Bladder dysfunction Retention or incontinence Common pathway: disablement in 10-15 years

Myasthenia Gravis Neuromuscular junction disorder; grave muscle weakness Decrease in surface area & increase in gap of neuromuscular junction Lack of Ach or Ach receptors= lack of AP Muscle fatigues rapidly during repetitive muscle use (10-20X longer) Treatment Increase in acetyl cholinesterase Neostigmine o Weak nerve gas o Destroys the esterase causing the Ach to stay in the synapse longer) May be an autoimmune disorder; remove thymus symptoms are reduced Clinical signs and symptoms: Rapid, profound muscle fatigue Loss of power with any repetitive action Long recovery time Tensilon test: o Rapid activity inject tensilon recover in 30 seconds o Anti-cholinesterase- allows Ach to build up For 90%, first symptoms in eye muscles o Ptosis: dropping eyelid o Diplopia: double vision and loss of depth perception Heavy feeling limbs (arms and legs) Chewing and swallowing difficult (nose regurgitation possible) Breathing inhibited (repetitive action) o Inability to clear secretions o Some die of respiratory fatigue Cerebral Vascular Accident (CVA) Stroke 3rd leading cause of death in the United States Anoxic encephalopathy: brain cell death at random 20% of the bodys oxygen is utilized by the brain & constant circulation is required for glucose (brain food) The brain is vulnerable to [localized] hypoxia, which causes CVA. Hypoxia in the brain can be caused two ways: infarct or hemorrhage, both caused by blood clot, which is usually caused by atherosclerosis or hypertension. 28

Defenses that help to prevent tissue damage: Cerebral vasodilation: If there is decreased PO2 (partial pressure) or a decreased BP as well as an increased PO2, then the dilation automatically occurs Collateral circulation: As ischemia develops, the body begins to develop altered circulatory routes to the same area. Other vessels slowly vasodilate and blood can enter from other pathways. This takes time, and it is often found in the Circle of Willis. It can lead to unusual connections. Enastimosis Infarct: blockage resulting in ischemia and tissue damage; localized *myocardial infarct: heart attack Thrombus (stationary clot that adheres to the vessel wall; composed of fibrin and blood cells) thrombosis (blockage) o Predisposing factors: Atherosclerosis: buildup of blood vessel plaque that activates clotting factors; most common type of artery blockage o Most frequent site of plaque build-up is arterial branches o Hyperlipidemia & diabetes o Wettable surface induces blood clots Hypertension blood vessel rupture Age Cigarette smoking Embolus: anything flowing in the blood (clot, plaque, air, etc.) o Heart is the primary source o Typically formed during atrial fibrillation Slowed blood flow Clots are apt to form in the heart and break loose o Clinical S&S: Sudden onset More damage than thrombus o No time for collateral circulation Confusion; consciousness may be lost May lead to hemorrhagic infarct & stroke o Brain tissue and blood vessel(s) die o Clot is reabsorbed o Clot flows back into weak vessel & hemorrhages

Intracranial hemorrhage: profuse bleeding inside the brain; localized damage 3rd most frequent cause of CVA Highest death rate Typically inside brain substance proper or subarachnoid mater 29

Usually follows long-standing hypertension, often from exertion or emotion Saccular aneurysm: (Berry aneurysm); tunica intimae is the only layer left of a blood vessel; often found in the Circle of Willis Clinical S&S: o Sudden onset o Typically involves an intense headache, possibly vomiting, and unconsciousness within minutes o Contralateral hemiplegia: paralysis on the side of the body opposite the cerebral stroke; flaccid to spastic o Usually blood is present in the CSF o Poor survival rate o 80% bleed into cerebrum Pool of blood expands rapidly & can bleed into entire hemisphere Bleeding in the lateral ventricle = death o Might develop into massive cerebral edema, leading to herniation (parts of the brain are shoved into places they should not be)

Herniation of the Brain Protrusion of a bodily structure through the wall that normally contains it Falx cerebri & tentorium cerebelli: meninges between and below cerebral hemispheres One cerebral hemisphere is shoved through the falx cerebri to the other hemisphere. The medulla is shoved through the tentorium cerebelli to the foramen magnum. Note: Circle of Willis Sits in the middle of the brain pan Best chances of collateral circulation Best chances of thrombus formation Basallar artery: where vertebral arteries connect to the coratid Transient Ischemic Attack (TIA) Mini-stroke Slow/partial blockage of blood flow Collateral circulation Stroke-like S&S, then return of function Temporary episodes of contralateral hemiparesis, contralateral hemiparasthesia (sensory disorders), and ipsilateral monocular blindness (one eye) May cause aphasia Transient contralateral paralysis: hemiparesthesia (paralysis on one side) and ipsilateral monocular blindness Thrombotic Stroke Same S&S as TIA, but they do not recede Gradual onset Do not lose consciousness 30

Related to atherosclerosis

Central Nervous System Infections Meningitis: meningial inflammation (dura, arachnoid, and pia mater) Spinal meningitis: meningitis of the spinal cord Encephalitis: infection of parenchyma of the brain (neural tissue) Parenchyma: functioning tissue Myelitis: Infection/infalmmation of the spinal cord (ex. polio myelitis) Encephalomyelitis: infection of the entire CNS (brain and spinal cord) Head Trauma Closed Head Trauma Dura mater is intact; possibly skull fracture Coup injury: injury on the same side of the brain as trauma Contracoup injury: injury to the opposite side of the brain as trauma Edema of the brain: fluids collect in the brain; must be controlled, or can destroy brain tissue Concussion: loss of consciousness with no structural brain damage (transient = <5 minutes) Contusion: bruising of the brain; small amount of blood leakage Laceration: actual tearing of brain tissue Buildup of edema and fluids (increased pressure) Epidural hematoma: hemorrhage between the brain and the skull Typically an arterial bleed Can cause pressure problems Stroke-like symptoms can occur Can cause herniation Can cause headache, confusion, and vomiting Subdural hematoma: hemorrhage between the dura mater and arachnoid mater Typically a venous bleed (can cause clots) Acute form: accident/skull fracture Chronic form: elderly/alcoholics Pressure May cause confusion, headache, and/or coma Can cause temporal herniation

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Open Head Trauma Skull fracture and torn dura mater Usually lose consciousness Requires surgery ASAP Same S&S as closed head trauma Cardiovascular System Route of blood through the body: Oxygenated blood leaves the lungs through the left pulmonary vein. Blood enters the left atrium and travels through the mitral valve to the left ventricle. Blood travels through the aortic semilunar valve in the aorta. The aorta leads to systemic circulation (arteries to capillaries). Venous end of capillaries carries unoxygnated blood to the vena cava. Blood enters the right atrium. Blood travels through the tricuspid valve into the right ventricle. Blood flows through the pulmonic semilunar valve to the left pulmonary arteries. Arteries enter the lung (right or left) and become oxygenated. Pulmonary circulation: supplies blood to the lungs to be re-oxygenated; occurs specifically in the bronchioles Systemic circulation: supplies blood to the body (except lungs)

Heart Anatomy Left heart systemic circuit Right heart pulmonary circuit (lungs) Ventricle: chamber of the heart that pumps blood from the atrium out of the heart Atrium: chamber of the heart that pumps blood into the ventricle Auricle: small conical pouch projecting from the upper anterior portion of each atrium Arteries: carry blood away from the heart Veins: carry blood to the heart Papillary muscle: in the ventricles; extension of the myocardium that pulls the cusps (leaflets) together and downward at the onset of ventricular contraction, thus preventing backward expulsion into the atria; attached by chordate tendineae Chordae tendineae: connective tissue that connects the papillary muscle to the leaflets; stabilize the leaflets and keep them from leaking

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Diastole: the heart is in a period of relaxation and dilation AV valves open Semilunar valves closed Greater pressure in the atria than in the ventricles Blood flow: atrium ventricle Systole: the heart is contracting AV valves closed Semilunar valves open Greater pressure in the ventricles than in the atria Blood flow: ventricle atria (AV valves close to prevent backflow)

**Systole and diastole is based on ventricles. This is common practice. Heart Valves Semilunar valves: aortic and pulmonic valves Thick leaflets can hold pressure; do not have chordae tendineae o Aortic valve: left ventricle aorta o Pulmonic valve: right ventricle pulmonary artery Sinus of valsalva: U-shaped valley between the arteriole wall & the aortic valve A-V valves: mitral valve & tricuspid valve Thin tissue Stabilized by papillary muscle & chordae tendineae o Chordate tendineae: threadlike bands of fibrous tissue that attach on one end to the tricuspid and mitral valves and on the other end to the papillary muscles, which anchor the valves Left atrial-ventricular valve (left A-V valve) o Aka bicuspid/mitral valve Right atrial-ventricular valve (right A-V valve) o Aka tricuspid valve

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Definitions Preload: related to ventricular end diastolic pressure and ventricular end diastolic volume; as ventricular volume increases, pressure increases; therefore, preload increases (increased work ventricle has to do to initiate contraction) Afterload: related to arterial end diastolic pressure and arterial end diastolic volume; as arterial volume increases, pressure increases; therefore, afterload increases Cardiac output (CO): stroke volume (SV) multiplied by heart rate (# of beats per minute); usually 5 L/min (up to 25 L/min during exercise); levels necessary to maintain adequate tissue oxygenation Ex. SV=70 mL/beat & pulse=72 beats/minute; CO=5,040 mL/minute (5 L/minute) Cardiac index: related to body surface area; cardiac output (CO) divided by body surface area; should be about 2.8 to 3.3 L/min/m2; surface area is equal to (0.11 X body weight)2/3 Ejection fraction: stroke volume (SV) divided by ventricular end diastolic volume (VEDV); ratio of the blood starting in the heart that was actually pumped into the body; measure of efficiency of the heart; as stroke volume decreases or VEDV rises, EF decreases (and vice versa) Total peripheral resistance/systemic vascular resistance (TPR/SVR): total resistance to blood flow through blood vessels of the systemic circuit; vasodilation= decrease in TPR; vasoconstriction= increase in TPR; heavily influenced by oxygen levels in the tissues Mean arterial pressure (MAP): equal to cardiac output (CO) times total peripheral resistance (TPR); average blood pressure in arteries; constant for activity taking place (compensation occurs) If TPR decreases, CO increases; If CO decreases, TPR increases Ventricular end diastolic volume (VEDV): the volume in the ventricle at the end of diastole Ventricular end systolic volume (VESV): the volume in the ventricle at the end of systole Stroke volume (SV): VEDV-VESV Phonocardiogram: records the sounds of the heart Handout Left heart through one heart beat: Semilunar (aortic) valve opens. Mitral (A-V) valve closes. Semilunar (aortic) valve closes. Dicrotic notch: area on the EKG when the aortic valve closes, blood slams into the newly closed valve the blood is forced out of the aorta. Mitral (A-V) valve opens. Ventricular systole ends when semilunar valve (aortic/pulmonic) closes.

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Heart noises: 1st and 2nd are normally heard in a healthy person. 3rd heart noise (faint sound of blood swishing into the heart) is not normally heard in a healthy person without a phonocardiogram, but it is there. It is called a ventricular gallop. If you can hear it, it is usually a pathology. 4th noise is called an atrial gallop. It is considered a pathology, and it is believed to have to do with resistance to ventricular filling.

Electrocardiogram (EKG/ECG) Movement of blood through the heart chambers P: Depolarization of atrium (inside to +) Reaching action potential Movement of depolarization through cells QRS complex: Depolarization of ventricles (inside to +) Initiates ventricular contraction ST: Ventricle contracts T: Repolarizaiton of ventricles (inside + to -) Beginning of ventricular relaxation Cardiac Conducting System Purkinje System Electrical path in the heart AV node & Bundle of His are the only pathway for electrical conduction (AP) from atrium to ventricle *See figure 13-5: The events of the cardiac cycle. 1. SA node AP initiated Atrial systole 2. AV node Conducts AP slowly (1/10 second from one side to the other) Delays ventricular contraction, allowing the atrium to fill 3. Bundles Conduct AP rapidly 35

4. Purkinje fibers 5. Up both sides (apex to base) & out of the great vessels Similar to squeezing toothpaste out of a tube Atrial kick: forceby atrial contraction before ventricular systole that increases the efficiency of ventricular ejection due to acutely increased preload; fills ventricle from 80% full to 100% full Splitting times: time between the first and second heart sounds Normal: o Exhalation- shorter splitting time o Inhalation- longer splitting time Abnormal: o Paradoxical splitting Aortic valves close late Longer splitting time during exhalation Left bundle branch block causes AP to reach the left ventricle late compared to the right side o Aortic Valvular Stenosis Prolonged dejection Difficult to get blood through the left semilunar valve Semilunar valve does not open fully due to scarring o Ventricular gallop rhythm Third heart sound louder Du du du = galloping horse o Atrial gallop rhythm Possible fourth heart sound Atrial systole Due to high resistance to ventricular filling (heart disease)

Note: Pressure is very different on either side of the heart, but blood volume pumped is the same. Cardiovascular Disorders High Output Heart Failure If TPR falls sufficiently, the heart cannot pump out a sufficient amount of blood, so CO increases and overexerts the heart. Pathologies: o Ex. anaphylactic shock (massive vasodilation), anything that causes extremely low tissue oxygenation (pulmonary disease, anemia, Beri Beri [B1/thiamin deficiency that causes systemic vasodilation])

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Low Output Heart Failure If there is severe hypertension, TPR could rise enough to cause low output failure; usually related to weakening of the heart Myocardial infarction (MI): blockage of blood flow causing ischemia, and the heart dies Valvular heart disease: problem with the heart valve leading to its not working properly o Stenosis of the valve Narrow valve; when it opens, it cannot open enough; could be due to scarring of the valve; could be congenital; less blood is permitted through the valve, causing increased blood pressure o Regurgitation (valvular incompetence/insufficiency) Leaky valve leading to the backwards direction of blood flow (aorta ventricle) o Cardiogenic Shock Cell deathMI gets bigger and weaker BP crashes shock Progresses in circles Cardiac Factors Regulating Cardiac Output CO= SV X heart rate Heart Rate: Autonomic Nervous System Sympathetic NS increases heart rate through beta receptors Parasympathetic NS decreases heart rate Stroke Volume Increased sympathetic NS activity Increased VEDV (Sterlings Law) Changes in heart rate (until it doubles) are most important; after it doubles, SV is the most important If the heart is pumping faster, the time between heart beats is less, causing SV to fall at very high rate During systole, there is very little blood flow in the muscles because the pressure is high. During diastole, there is maximum blood flow in the muscles because the valves are closed. Note: Max blood flow in the coronary vessels is during diastole. Therefore, if the heart rate is too high, then the heart does not have time to let the blood flow in the coronary vessels. The heart is being starved for oxygen, which can lead to an infarct.

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Starlings Law of the Heart: VEDV SV If you pump more blood into the heart, then the heart will pump more blood out (to a certain point). Percent Muscle Length Why? o As muscle stretches, it gets weaker because sarcomeres stretch & actin/myosin filaments no longer overlap each other and cannot form cross bridges. o As VEDV increases, the muscle is stretched and is contracted with more force, increasing SV. o Intrinsic control: automatic (no NS/hormones involved) o SV is heavily dependent on VEDV, which is heavily dependent on the amount of venous return.

Blood Pressure Things that Regulate/Change Blood Pressure Control CO Control resistance (vasodilation and vasoconstriction) Control blood volume Water intake (drinking) Defecation Sweat Exhalation o More water is lost during exhalation than is gained during inhalation. Urination o Kidneys are major blood volume controllers. **Note: Cardiac/respiratory/kidneys- If one fails, then the other two will soon follow. Secondary BP Control Capacitance System Internal carotid artery blood supply to brain External carotid artery blood supply to face Aortic arch vagus nerve medulla Carotid sinus: stretch receptor inside the internal carotid artery; contains neural stretch receptors passing through Herings nerve and the glossopharyngeal nerve to the medulla (vasomotor centers) Medulla can then play games with autonomic NS to get BP close to normal using action potentials (negative feedback) Short-term BP control; keeps constant blood flow to brain from moment to moment

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Baroreceptor: located in carotid sinus and aortic arch; (*carotid sinus & aortic arch are interchangeable in negative feedback mechanism)
AP @ medulla (vasomotor center) -Sympathetic NS

BP @ coratid sinus (CS stretches)

+ Parasympathetic NS

BP

CO

heart rate

BP BP BP CO

CO

SV

or

HR

+ resistance SV

+ vasodilation VEDV venous return

If BP increases: Carotid sinus stretches. There is an increase in action potentials in the vasomotor center of the medulla. Vasomotor centers in the medulla interpret the APs. Autonomic NS is activated. Parasympathetic NS: o Decrease in heart rate o Decrease in CO o Decrease in MP o PNS inhibited Sympathetic NS: o Decrease in heart rate or decrease in SV o Decrease in CO o Decrease in BP o Vasodilation o Increase in resistance o Decrease in BP o o o o o o Vasodilation Decrease in venous return Decrease in VEDV Decrease in SV Decrease in CO Decrease in BP

**This system sets itself to normal, so it can be set to a hypertensive state 39

Primary BP Control Renin-Angiotensin System Kidneys induce hypertension most. Massive BP control by kidneys 1 million nephrons/kidney Juxtaglomerular apparatus: measures BP/flow through afferent arteriole to glomerulus When the juxtaglomerular apparatus detects a decrease in BP, renin is released into the blood through the efferent arteriole. Renin: a hormone with enzymatic activity that circulates body-wide; binds and activates angiotensinogen, splitting it into angiotensin I Adrenal cortex: wrapped around the medulla; makes steroids, mainly aldosterone Angiotensin II: massive vasoconstrictor (increases BP) ACE inhibitors: treatment for BP control; block ACE, which converts angiotensin I into angiotensin II Aldosterone: hormone made in the adrenal cortex that stimulates the active transport of sodium from the nephron back into the body Coupled to the active transport of potassium from the body into the nephron (sodium out of nephron and potassium into nephron) More sodiums return to the body than potassiums are lost from the body, causing a net solute movement into body, which causes osmosis (passive diffusion), a net outflow of water. There is now more fluid in the body, which means more blood in the body and increased BP.

Renin-Angiotensin System
BP @ afferent arteriole BP + Juxtaglomerular apparatus Renin released @ afferent arteriole Angiotensin II Aldosterone released from adrenal cortex Angiotensinogen (binds to) Angiotensin I

+vasoconstriction Na+ reabsorption from nephron H2O reabsorption

ACE*

blood volume

If blood pressure decreases: JG apparatus releases Renin. Renin binds to Angiotensin (protein in blood), splitting it into Angiotensin I. 40

Route #1: Angiotensin I is split into Angiotensin II (active) by ACE (Angiotensin converting enzyme) This stimulates vasoconstriction. Increased resistance to flow increases blood pressure. Route #2: Angiotensin II stimulates the adrenal cortex. Adrenal cortex releases aldosterone (to nephrons). Aldosterone stimulates Na+ and H2O reabsorption at the distal tubule of the nephron. Blood volume is increased, which increases blood pressure.

WHAT IF there is severe renal artery atherosclerosis (arteriosclerosis)? BP increases (SV and pulse pressure) until kidney considers the BP higher than normal. Less blood gets in, so blood pressure decreases in the kidney. Juxtaglomerular apparatus is stimulated & BP is driven up to make JA BP normal. The rest of the body has severe hypertension because the kidneys have changed what BP is normal (above what the body is used to). If ACE inhibitors block that step, BP gets down to normal. Definitions: Blood pressure: systolic pressure/diastolic pressure Normal 120/80 120=systolic, 80=diastolic Pulse pressure: Systolic pressure diastolic pressure Typically higher SV= higher pulse pressures Compliance (of the arteries): measure of elasticity of an organ (blood vessels); volume / pressure Compliance is good. No compliance=ultimate hardening of arteries and increase in heart size; greatly increases systolic pressures; increase in pulse pressures Loss of compliance means pulse pressure increases (change in SV) Hypertension: high blood pressure Difficult to define hypertension; insurance defines it as: Systolic > 140 Diastolic > 90 Normal can be as high as 160/100 for elderly people (BP tends to increase with age) Signs and symptoms of heart problems: Angina: precordial pain: pain in upper chest and sternum; pain of ischemic muscle, commonly pain in left shoulder and arm (referred pain from heart); caused by anything causing ischemia of the heart Pulmonary edema: collection of fluid in the lungs; anything that limits venous return to the left heart can lead to pulmonary edema; blood cannot get into/out of heart (most 41

likely severe left side heart failure); alveoli fill with fluid (transudate) and can cause drowning; breathing is difficult, which leads to dyspnea Dyspnea: difficulty of breathing, especially during exercise Orthopnea: dyspnea in which breathing is difficult in the recumbent (horizontal) position, not in the upright position; gravity-induced/postural issue; lay propped up on pillows or sleep sitting up Paroxysmal nocturnal dyspnea: awaken with a sudden shortness of breath and wheezing respiration; orthopnea that has a gradual onset and reset; seen in people with severe left side heart failure Peripheral edema: body-wide systemic edema; very rare; collection of blood in the systemic circuit capillaries, so that blood cannot get back to the right heart (typically secondary to left-side heart failure); happens where gravity aids (e.g. feet and legs); typically you see renal failure at the same time (requires blood pressure to operate) Palpitations: heart gets out of rhythm (beats out of time); recurrent palpitations can lead to heart problems Syncope: transient loss of consciousness (fainting); can be caused by inadequate blood flow to the brain Fatigue: weakness due to inadequate cardiac output; tired

**Using these S&S, you can classify kinds of heart failure. Progressive heart failure: Weak heart Decrease in SV Decrease in pulse pressure Increased sympathetic NS activity Vasoconstriction Increased diastolic BP (mean BP falls over time) *indicates left side ventricular dysfunction Severe hypertension without atherosclerosis (have elastic arteries) Fully extended at diastolic BP, cannot expand for systolic BP Behaves like arteriosclerosis **Major athletes- increased pulse pressures WHAT IF stroke volume decreases? Decrease in systolic pressure Decrease in pulse pressure To fix- stimulation of vasoconstriction & increase in diastolic pressure New York Heart Association Guidelines for Patient Classification (for heart failure) Class 1: asymptomatic with ordinary exertion Class 2: symptomatic with ordinary exertion Class 3: symptomatic with less than ordinary exertion Class 4: symptomatic at rest

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Valvular Problems: Stenosis: valve that does not open properly and/or Regurgitation: valve that does not close properly (leaky valve) **These can happen at the same time. Scarring secondary to Rheumatic Fever: (Ag-Ab complexes cause body-wide inflammatory responses, including inflammation in joints that cause Rheumatoid Arthritis-like symptoms Involves stenosis and regurgitation Leads to death by heart failure Valvular hamstring: huge enlargement of the atrium, leading to regurgitation in the mitral valve Syphilis: can cause aortic regurgitation Congenital problems leading to stenosis (e.g. lack of leaflet) = developmental foul It is possible to have multiple valvular diseases. This is more likely to happen on the left side and in lightweight valves (A-V) because of greater pressures. Therefore: 1. Mitral valve 2. Aoritc valve 3. Tricuspid valve 4. Pulmonic valve

Handout: Pathophysiology of Valvular Heart Failure: Mitral stenosis, mitral regurgitation, and aortic stenosis & regurgitation Mitral Stenosis Stenotic valve does not fully open High velocity of blood flow through the narrow opening Turbulent flow = ventricular diastolic heart murmur Presystolic murmur: diastolic murmur that can only be heard during systole Blood collecting in the left atrium and the mitral valve cannot all get into the ventricle due to a narrow mitral valve (low SV). As the left atrium dilates, it contracts with more force and hypertrophies. A long P-wave notch may develop. If the muscle of the left atrium is strong enough to push normal blood flow through the valve, then compensated heart failure occurs. If it is not strong enough to get enough blood into the ventricle: Pressure in the lungs and pulmonary circuit will rise above normal to get more blood into the atrium, forcing excessive plasma into capillaries. Pulmonary venous congestion Pulmonary congestion Pulmonary hypertension (edema)

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The right heart now dilates and contracts harder to get the blood through the lungs in order to compensate the left mitral valve weakness. Blood flow could get back to normal. If the right atrium is not strong enough to push an adequate amount of blood out, the right atrial pressure rises, it dilates, and hypertrophies. If the right side fails, pressure in systemic capillaries rise and you could develop systemic edema. Ascites: collection of fluid in the abdominal cavity that could happen in systemic edema

Review: Right heart failure = systemic capillary pressure rises/systemic edema Left heart failure = Pulmonary capillary pressure rises/pulmonary edema Dilation of the atrium could also cause the valve to leak, and during ventricle contraction blood could flow backwards. This would make the failure more serious. If the atrium is too enlarged, you could have atrial fibrillation that could eventually lead to ventricular tachycardia. Mitral Regurgitation o Leaky mitral valve o Ventricle contracts and some blood goes into the aorta, while some goes back into the atrium. o Stroke volume falls. o The blood that went back into atrium goes back into the ventricle, and the left ventricle enlarges to get more blood into the aorta. o Eventually left ventricular hypertrophy occurs to compensate. If it works, there will be normal systemic blood pressures. o If the ventricle cannot get normal stroke volumes, then blood collects in the left ventricle, and the left atrium dilates and hypertrophies to get more blood flow from the ventricle to the aorta. o The left atrium cannot get all the blood out, so it collects in the atrium. o If it fails, pulmonary circuits rise and edema occurs. Pulmonary venous congestion Pulmonary congestion Pulmonary artery hypertension o As pulmonary pressures rise, the right heart begins to fail. It dilates and hypertrophies. o The murmur will be systolic and quite obvious. Blowing murmur: swishy, high frequency murmur **The difference between Stenosis and regurgitation: Regurgitation has ventricular hypertrophy and stenosis does not; greater increase in stroke volume in regurgitation. Fulminating Pulmonary Edema: rupture of the papillary muscles; the valve leaflets are not controlled and could swing backwards. Therefore, you will have massive regurgitation and almost immediate pulmonary edema occurs.

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Aortic Stenosis & Regurgitation Net stroke volume will fall in the aorta. Less blood is getting out. Initial problem: left atrium will collect fluid and left ventricle will contract with more force. Left aortic valve has a problem- left ventricle dilates and hypertrophies. Compensated heart failure: If the left ventricle dilates enough to compensate, the problem is solved. The left atrium then dilates and hypertrophies to push more blood into the left ventricle. If it cannot compensate, the pulmonary circuit pressures rise and edema occurs. The right ventricle contracts harder, dilates and hypertrophies. Systemic edema and capillary pressures rise. Heart failure Mitral regurgitation, aortic valve regurgitation, and aortic valve stenosis are all the same! Note: flow through the coronary arteries is at maximum in diastole. Signs and symptoms: Angina Water hammer pulse: huge, sudden pressure changes o Huge SVs o Enormous systolic pressures o Decreased diastolic pressures o Huge pulse pressures Quinkes Capillary Pulsation: If you have severe regurgitation, during diastole the systemic capillary pressures comes to a halt and nail beds will be white in diastole and pink in systole. Thrill: loud systolic murmur; can be heard in severe cases several feet from the patient; can also be felt as a vibration on the upper chest or neck (due to aortic stenosis and a high velocity of blood flow) Tricuspid Valve Stenosis and Regurtitation Right atrium dilates and hypertrophies. Systemic edema and high pressures in systemic capillaries occur due to a build- up of the right heart and strong, normal functioning of the left heart. Systemic edema will be severe. These people could look anorexic (due to the GI engorgement of fluid) They could also have a taller than normal P-wave (P-Pulmonale?) because of an enlarged right atrium. Pulmonic Stenosis/Regurgitation Pulmonary valve has problem The right ventricle dilates and hypertrophies. The right atrium dilates and hypertrophies. Severe systemic edema occurs.

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Valve Replacement

Other Heart Definitions: Sclerosis: was first mentioned by Leonardo daVinci Atheroma: Pourige; primarily a disorder or a disease of large arteries, with lipids deposited in and under the tunica intima (in the epithelial layer of blood vessels) Atherosclerosis: Coined in 1904 Primarily a disorder of large arteries Lipids are deposited in and under the tunica intima Plaque build-up due to fibrous build-up joins the lipids In severe cases calcium could also be deposited, making the blood vessels like concrete. Not common in women until after menopause Following menopause or hysterectomy, womens cholesterol skyrockets. Plaque tends to be laid down at the beginnings and branches of blood vessels. People do not have clinical symptoms until the artery is 60-75% closed. o The resistance is exponential. It will change by the 4th power of the diameter of the lumen of the vessel. o Could develop an acute occlusion: blood clots can develop over the atherosclerosis and completely block the blood flow This could also cause a thrombus, which can loosen and cause an embolism. o Could also have a hemorrhage of an artery due to weakness caused by the plaque The hemorrhage fills the plaque with blood which will swell and close the blood vessel. o Could also develop a coronary spasm 46

The critical areas for atherosclerosis o Major branches of arteries and arterioles Weakness in the vessel walls could cause aneurysms in the brain due to blockage of vessels and stroke. In kidney: blocks blood flow in kidney; cannot properly produce urine and hypertension occurs.

Aneurysm Weak blood vessel wall just before blockage (bulging) Atherosclerosis occurs, blocking the blood vessel and causing it to swell. The walls are weak and they break. False: A ruptured blood vessel causes the connective tissue around it to swell. Multiple kinds: Dissecting aneurysm: the tunica intima is broken, and blood is forced under it, causing it to separate and close off the vessel

Coronary Arteries Left anterior descending artery Circumflex branch Right coronary artery Right posterior descending branch Crux of heart: o Whatever cardiac artery crosses over the crux of the heart, supplies blood to the A-V Node. o Right Dominant: 90% RCA crosses o Left Dominant: 10% LCA crosses SA node is supplied by the RCA or the circumflex. Collateral Circulation is possible in the heart.

Coronary Veins Great cardiac vein Coronary sinus: into the right atrium Middle cardiac vein Small cardiac vein **Note: All veins go into the coronary sinus.

Pathophysiology of Coronary Arteries: Angina Pectoris: strangling of the chest; caused by ischemia of the heart muscle Causes: effort, emotion, cold weather, meal, smoking 47

Relieved by: Nitroglycerine or Amyl Nitrite, which cause vasodilation 1/3 of all deaths are related to Coronary Artery Disease (most likely a thrombus, but can be atherosclerosis or infarct) Without oxygen, the muscle dies. The severity depends on location. Septum is the most dangerous because left and right branch of bundle of His is there. As muscle dies, it relaxes because it cannot contract anymore. Transmyral Infarct: all the way across the wall of the muscle Subindocardial Infarct: infarct does not go all the way through the muscle Stages of Recovery: The dead cells are reabsorbed. Systolic Stretch: The wall thins, then balloons out during contractions. Cardiac output decreases, as well as stroke volume, due to the stretch. Fibroblasts come in and lay down the scar tissue (fibrous connective tissue). This area never contracts, so the other muscle around it hypertrophies to compensate. Blood clots have a tendency to form in the scar tissue, then can become an embolism. Problems go backward from damaged area: Left ventricle fails, left atrium hypertrophies, pulmonary edema occurs, right ventricle hypertrophies, and so forth. Cardiac Tamponade: During systolic stretch, it can blow, filling up the pericardial sac (does not stretch), causing heart to be unable to contract. Pansystolic Murmur: septum infarct that ruptured; left side contracts causing too much pressure to go into the right heart, blowing it out. Papillary Muscle Infarct: Papillary muscle ruptures, which causes the chordae tendineae to detach from the muscle. The valves are no longer being held in place, and the pressure blows out the atrium.

Problems with Muscle Infarcts: Cells surrounding the myocardial infarct barely get enough oxygen. MI cells leak their insides out into the surrounding area (neutral but behave like area). MI cells start to pull + charges into surrounding cell membranes, meaning less changes are needed to fire the AP. Therefore, they are more likely to fire at the wrong time (not in rhythm with surrounding cells). Leads to extra-ventricular beat (Premature Ventricular Contraction, PVC) Circus Movement: PVC that wanders around the heart (often times enlarged hearts) until it meets at the first cell that caused the fire again; repeats pattern until the cells die o Fibrillation: the heart has random firing, and it dies from lack of oxygen Stop here for test #2.

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Test Three Results of Ischemia and Infarct HR BP EKG: Inverted T-wave Modified S-T segments Angina Depressed left ventricular function contractility SV EF VEDV VESV wall compliance after healing To heal: Rest (decrease the amount of O2 needed) Digitalis or beta-simulating drugs to increase CO These might increase the infarct (require more O2), which could kill the person. No infarct, just Angina: sympathetic blocking agents (propranolol and nitroglycerin), which lower the BP and pain. Reduces heart function Coronary-artery bypass surgery Compensated Heart Failure (chronic): BP glomerular filtration rate Filter less plasma urine production fluid volume blood volume BP Stimulate renin angiotensin system blood volume venous return VEDV SV (Starlings Law) Collateral circulation (without infarct) oxygenation and feeding of tissues Ventricular hypertrophy Increased SV 49

During acute phase- sympathetic NS activity Fast pulse Cold, sweaty, pale skin (pallor) o blood flow Could return to normal, resting CO If not fixed, congestive heart failure occurs. Compensated heart failure: the heart changes (e.g. hypertrophy) so that the MAP is close enough to normal that there are not any problems (e.g. edema); the person can then live a normal life Decompensated heart failure: the change(s) do not increase the MAP high enough to compensate, which leads to congestive heart failure Compensation can be dilation of a chamber, This would have a negative effect. La Place relationship: As the ventricle dilates, the heart must develop more tension to compensate (ventricular tension= arterial pressure X ventricular radius). o The person would need more ATP to increase the tension, but the blood is not there to provide it. Dilation is good to a point, but after that it causes damage. Simultaneously, the following occur: ventricular tension = preload hypertension + ventricular tension = afterload If the body still cannot maintain adequate blood pressure and CO after all compensations to the heart are made, there is congestive heart failure.

Congestive Heart Failure glomerular blood pressure ( overall BP) filtration urine production H2O in body Edema, right side dilation, left side function (e.g. A-V valve regurgitation) CO The heart does not pump enough blood out, so there is pulmonary and/or systemic edema (alveoli and body fill with fluid). Bubbling Rales (pronounced rols): bubbling sound heard through a stethoscope caused by fluid in the alveoli of the lungs

Treatment CO Digitalis or beta-agents heart rate Note: This can cause damage if the the heart is pushed too hard. fluid volumes Diuretic: increases urine production so that fluids leave the body H2O intake (drinking or IV) 50

Na intake, which decreases water retention Take out blood (e.g. rotating tourniquets) O2 intake The heart does not have to work as hard. Heart transplant Note: must be in good shape otherwise

Pulmonary Congestion

Systemic Congestion (enlarged liver)

Review: Left side failure = pulmonary edema Ride side failure = cyanosis: blue color resulting from a lack of O2 in Hb due to a lack of systemic blood flow Systemic edema: o Engorged jugulars veins o Enlarged liver o Ascites: collection of fluid in the abdominal cavity o Increased venous pressure Types of heart failure Outflow disorders- difficulty getting blood out of the heart Left side o Aortic stenosis: narrowing of the aorta

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o Coarctation of the aorta: narrow, stenosis-like area of a blood vessel; generally congenital o Systemic hypertension (#1 cause of left side outflow disorder) Right side o Left side failure (#1 cause of right side outflow disorder) o Pulmonic valve stenosis o Cor pulmonale: pulmonary hypertension (not caused by left side failure); caused by a problem in the lungs (e.g. COPD) Note: COPD = asthma, emphysema, chronic bronchitis o Pulmonary embolus (probably a right heart clot) o Vasculitis of pulmonary circuit: blood vessel inflammation size of lumen of the blood vessel BP Inflow disorders- difficulty getting blood into the heart Left side o Pulmonary artery obstruction (outflow disorder for right side) o Thromboemboli: thrombus that becomes an embolism o Pulmonary parenchymal disease: difficulty getting blood into the lungs o Left atrial thrombus/tumor o Mitral stenosis Right side o Constructive pericarditis: fibrous scarring with occasional calcification of the pericardium; inflammation of the pericardium between the epicardium and the parietal pericardium (layer of exudate/transudate); encases the heart in a rigid shell, keeping it from expanding; similar to tamponade o Vena cava obstruction o Right atrial thrombus/tumor (limits blood flow to atrium) o Tricuspid stenosis (ventricle cannot fill properly) o Tamponade

Disorders of Systemic Circulation Coronary atherosclerosis Closes off lumen in circulation Common in areas with branches of arteries Intermittent claudication: pain upon exertion; ischemia of muscles due to atherosclerosis; blockage of artery feeding muscle above the area of pain The problem area can be discovered by pain upon exercise: o Pain in calf- atherosclerosis of superficial femoral artery o Pain in thigh- atherosclerosis of iliac artery o Pain in buttocks- atherosclerosis of distal aorta Signs and symptoms o Wasting of muscles o Thickened nails o Thin skin o Dry gangrene (ischemic cell death) 52

o Occlusion of blood vessel(s) Reduced or absent peripheral pulse Coolness of extremities (blood is not reaching skin) Auscultated bruit: murmur-like sound in the extremities near the area occluded blood vessel(s) o Arterial thrombus or embolus Arterial Disorders Raynauds Disease (Peripheral vasospasm): inappropriate constriction of arteries in the hands and feet (and possibly other extremities); ischemia and pain develop Reactive hyperemia: dilation of blood vessels, flooding blood into the area (sudden massive blood inflow = constriction massive dilation); leads to reddening of the skin and pain becomes more intense Normally not a serious condition Most often in women in cold weather areas Can cause gangrene in severe cases Treatment: o Sympathetic blocking agents o Sympathectomy: the sympathetic motor neurons to the extremities are cut Buergers Disease: vascular inflammation in which the lumen is forced to decrease in size due to a lack of room for expansion (Note: The nerve, artery, and vein run together and are bound together by a sheath.) Primarily young males (onset at 20-40) Ischemia leads to intermittent claudication Tobacco (smoking/chewing) worsens the disorder Fingers and toes can be lost Sympathectomy helps, but quitting smoking most often controls the problem Pain on exercise Venous Disorders Thrombophlebitis: thrombus formation in inflamed veins, usually accompanied by the pooling of blood; common in the legs Predisposing factors: o Venous stasis: lack of blood flow in veins; pooling of blood o Inflammation of the tunica intima clotting factors o Endothelial damage o Hypercoagulability: clotting more easily than normal, usually in legs Thrombus can break off and cause pulmonary embolus If thrombus stays put, it will degrade/heal & normal flow returns Signs and symptoms: o In superficial veins- redness, heat, & tenderness along vein o In deep veins- edema of extremity o Positive Homans signs: dorsi flexion of the foot (toes toward knee) leads to strong pain and sensitivity to pressure in an extremity (e.g. one calf) o Cyclic: each one aggravates the other (inflammation and edema) 53

Can lead to chronic venous insufficiency: destruction of vein valves leading to leaking and pooling of blood o Blood leaks backward (regurgitation) o venous return o Dilated veins with incompetent valves (varicose veins) o stasis o blood clots o Thrombophlebitis worsens o Tend to have edema and rupture of capillaries/blood vessels Varicose veins: set of veins that are weak/leaking Note: Other causes of varicose veins Genetics (wall weakness) Secondary to venous disease (e.g. thrombophlebitis) Edema and pigment collection o Secondary to capillary rupture o Secondary to pressure in veins? Pregnancy Vena cava smashed by vertebral column

Treatment o Acute: bed rest with limb elevation (to keep clot from moving) o Chronic: Exercise; elastic stockings, anti-coagulative drugs

Lymphedema: blockage of lymphatic vessels How do lymphatic vessels cause venous disease? o The lymphatic vessels serve as a drainage system. o The lymphatic system dumps back into the subclavian artery through the thoracic duct. o Very slowly proteins move out of the capillaries in excess to the tissues, causing edema as the tissues collect fluid. Causes of lymphedema o Filariasis: parasitic filarial worms, transmitted by mosquitoes, live in the lymph nodes and block lymphatic vessels Elephantiasis: heavy limbs (e.g. legs, scrotum) o Malignant lymphedema: blockage in a lymph vessel secondary to a tumor or a radical mastectomy (removal of breast tissue and lymphatic drainage); eventually subsides o Congenital lymphedema: lack of lymph nodes o Allergic lymphedema: blockage of lymph vessels due to an allergic reaction Signs and symptoms o Painless o Edema o Diuretics and elevation will not help 54

o Septicemia: infection of the entire body caused by bacteria emptying into the heart and being distributed throughout the body Treatment o Remove obstruction (e.g. tumor) if possible o Intermittent pressure devise that pushes on the area (at night) o Pressure gradient stockings

Hypertension: high blood pressure Kidneys control blood volume, which controls blood pressure. o Blood pressure buffering organs o 2% chronic increase in blood volume can cause a 30-57% increase in BP over time. o BP = urine production Carotid sinus has limited and short-term control over BP.
12 BP vs. Urine Output 10

Urine Output

8 6 4 2 0 0 50 100 150 200 Arterial BP (mmHg)

Types of hypertension o Renal hypertension: hypertension caused by kidney problems Renovascular hypertension (Goldblatt hypertension): hypertension caused by restriction of blood into the kidney (e.g. atherosclerosis of renal artery at afferent arteriole); the kidney keeps its BP normal, but the rest of the body has hypertension o Signs and symptoms Increased renin, angiotensin II, and aldosterone Renovascular hypertension without an increase in renin is due to normal blood pressure at the glomerulus in chronic cases Hypertension due to low kidney mass: caused by destruction of kidney tissue (renal parenchymal disease); can be up to 70% of kidneys mass before there are any signs of abnormal BP (stays within 6 mm of normal BP) o Extra fluid causes BP to increase o Salt intake keeps H2O in the body (blood volume=BP) 55

o If enough kidney mass is lost, BP increases enough that water stays in the body ( urine production) o Nephrons in kidneys will have higher-than-normal levels of uremia, waste product that is normally removed by the body Hypertension due to decrease in glomerular filtration rate (GFR): caused by a limited amount of filtered blood; the kidneys readjust so that waste exits, but water builds up in the body; develops hypertension without uremia build-up; Renovascular hypertension is an example o Blood vessel blockage o blood volume o Edema

o Coarctation of aorta: region of the aorta is narrowed; everything above the coarctation has hypertension (about 2X normal) and everything below has low BP; congenital Treatment o Surgically repair coarctation The carotid sinus is used to 2X the pressure, so it will drive the BP up to normal. (baroreceptors think BP is normal) The lower body is used to 1/2X, so it goes into hypertensive shock, which includes necrosis of the vessels in the lower body. The patient is given drugs to keep the BP down until the carotid sinus readjusts to decreased BP. o Pheochromocytoma: tumor of the adrenal medulla (produces hormones); tumor releases hormones at inappropriate times and epinephrine is elevated all the time May lead to chronic hypertension Paroxysmal hypertension: the tumor is cyclic and releases large amounts of hormones suddenly (normal BPBP) o S&S: anxiety, tachycardia (HR above 100), perspiration, nausea, epigastric (precordial) pain o Treatment: adrenergic blocking agents (e.g. beta blockers) o Primary aldosteronism (Conns Disease): small tumors of the adrenal cortex cause an excess of aldosterone to be produced Na+ movement out of the body (than K+ into the body) [Na+] in the body H2O reabsorption from nephrons blood volume/ BP o S&S: hypertension, hypokalemia ( [K+] in the body), kaliuresis ( [K+] in urine >30 mEq/day)

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o Different from acute cases of Goldblatt- Goldblatt has high renin levels in the system, and Conns does not o Cushings Syndrome: increased levels of glucocorticoids (e.g. corticoids from the adrenal cortex that controls glucose metabolism); very rare form of hypertension Aldosterone and cortisol are very similar. At very high concentrations, cortisol can cause hypertension like aldosterone. Pituitary tumors release ACTH, which stimulates the release of cortisol. o Essential hypertension: no known etiology; most common; increased TPR; most likely caused by kidneys Look at the arterioles of the internal eye (retinal ground) to see hypertension Grades: o Grade I: mild narrowing of arterioles; no excessive BP (normal BP at kidneys) o Grade II: increased sclerosis with narrowing at the crossing points; hypertension, but health is still good o Grade III: silver wire arterioles; arterioles have a silver appearance to them (dark outside lines and lighter middles); angiospastic retinitis: sustained hypertension and dyspnea; may have edema in optic disk with some hemorrhaging o Grade IV: further hemorrhaging and edema (both are present); develop proteinuria: protein in the urine; headaches; visual disturbances; dyspnea Electrocardiography Path of electric current following the depolarization of the heart *Study diagram of cardiac conducting system from test 2 Waves: P wave: atrial depolarization; contraction QRS complex: ventricular depolarization; ventricular contraction and atrial repolarization/relaxation T wave: ventricular repolarization/relaxation

Following the electric current through the body Put pins in the heart and hook it up to a meter (with paper) Electric current can be read from any part of the body (e.g. arms and legs)

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Limb leads Wiring of 3 standard limb leads: o Lead 1: L arm + and R arm o Lead 2: L leg + and R arm o Lead 3: L leg + and L arm + L

II

III

+ Precordial leads: unipolar (one positive electrode and multiple negative electrodes) chest leads; V1-V6 o 3 limbs (-) to (+) locations on the chest wall o Allows a close look at the heart V1: inverse QRS (right atrium) V3: split QRS; half up and half down (ventricles) V6: similar to lead 2; looks normal (side) Augmented unipolar limb leads: arms and legs (one limb positive and two limbs negative); letters describe which limb o aVR: right arm + (inverted) o aVL: left arm + (looks normal) o aVF: left leg/foot + (looks normal) Note: R= right arm, L=left arm, F=left leg/foot Refers to positive limb lead

Time scale of EKG Big boxes = 5mm x 5mm (0.2 seconds) Small boxes = 0.04 seconds The machine runs at 2.5 cm/sec (25 mm/sec) P wave: 0.08 seconds (2 mm) PR: 0.16 seconds (4 mm) o Prolonged if > 0.2 seconds (A-V node blockage) 58

QRS: 0.1 seconds (2.5 mm) o Prolonged if > 0.12 seconds ( ventricular depolarization time) QT: 0.36 seconds (9 mm) o Prolonged if > 0.6 seconds (bundle branch dysfunction)

Calculating heart rate from EKG 30 boxes (15 cm) o HR = # of cycles per 15 cm strip X 10 e.g. (7.5 cycles)(10) = 75 RR interval method o HR = RR interval (# of small boxes X 0.04 sec) X 60 (sec/min) e.g. (25 small boxes) (0.04 sec/box) = 1 second (60 sec/min) = 60 o Only works for regular heart rate (60-100 beats/min) o Bradycardia: HR below 60 o Tachycardia: HR above 100 Heart Rate 300 150 100 75 60 50

# of Big Boxes 1 2 3 4 5 6

Reasons for movement of EKG Depolarization toward + drives the line above the baseline Depolarization toward drives the line below the baseline Hypertrophy- QRS gets taller (AP) Damage to bundle branches- QRS gets broader ( time) Anything that extends QRS will be a pathology (blockage of conduction system) o Q: depolarization of septum o S: upper ventricular depolarization o T: repolarization (away from positive) Pathologies of EKG Arrhythmias: any disorder of heart rhythm; abnormal HR or conduction pathways reduce the ability to pump Irregularities of rhythm o Pacemaker o Conduction system (bundle branch) o Decreased ability of the heart to pump Subendocardial ischemia: S-T segment depression; accompanied by an inverted T-wave Transmural ischemia: S-T segment elevation Pritzmetal angina: transmural ischemia accompanied by constant pain 59

Some Abnormalities of EKG NOT ON TEST! Sinus tachycardia: P-wave and T-wave close together SA node driven rhythm (fast SA node activity) Sinus bradycardia: long T-wave to P-wave Premature junctional contraction (PJC): P-waves absent with normal QRS complex; premature A-V junction contraction Premature ventricular contraction (PVC): ventricles initiate heartbeat rather than SA node; shown on EKG by abnormality between QRS complex and T-wave Premature atrial contraction (PAC): R-waves close together; early heart beat initiated by SA node Atrial fibrillation: R-waves spread apart; A-V node driven at different points (random activity at atrium) First degree A-V block: P-wave to QRS complex is too long; A-V node conducting too slowly Second degree A-V block mobitz I: P-R intervals get larger until a beat is skipped Second degree A-V block mobitz II: P-R intervals consistent and then beat skips Third degree A- block: complete block; broad QRS complex; ventricular rate slower than atrial rate

Respiratory System

Anatomy of the Respiratory System Nose Pharynx and larynx Trachea: contains bands of cartilage, which keep the trachea open during inhalation Carina: point where the trachea branches (roughly 23 branch ducts from trachea) 60

Right and left primary bronchi Note: The right primary bronchus is longer and less angled than the left primary bronchus. Objects are more likely to fall into the right lung if sent down the trachea and launched into a lung. Segmental bronchi and bronchioles Terminal bronchioles: smallest bronchioles (conducting pipes); no gas exchange Respiratory bronchioles: gas exchange Alveolar ducts: look like branches of grapesalveoli Acinus: respiratory bronchioles, alveolar ducts, and alveoli; area of gas exchange Septa/septum: division of cells between alveoli; increase surface area, which allows for more gas exchange Pores of Kohn: openings between the alveoli; alternate route for gas exchange if alveoli are damaged; normally closed Lining of the respiratory system Visceral pleura: epithelial lining of the lungs Parietal pleura: epithelial lining of the thoracic cavity Serous fluid: layer of fluid within the lining of the alveoli that keeps the squamous epithelium moist and alive; mostly H2O, which has surface tension and forms itself into a solid sphere (least possible surface area) not good Surfactant: protein in the serous fluid that decreases surface tension, keeping fluid on the edges of the alveoli and prevents it from forming a sphere; one of the last proteins made before birth o Respiratory Distress Syndrome (Hyaline Membrane Disease): common disease of premature babies; lack of surfactant in the lungs; the lungs collapse, suffocating the newborn (born blue) Treatment: put surfactant down the trachea Can occur in adults (can be a result of drowning) Hemoglobin (Hb) Carries O2 on red blood cells o Biconcave disc shape more surface area speed of loading O2 onto Hb Anything that interferes with diffusion distance or the ability to diffuse (e.g. edema, scarring) will cause a problem.

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Respiratory Passageway Keeps the lungs clean Lined with moist, ciliated mucus-secreted epithelium (psuedostratified columnar epithelium). Cilia move mucus away from the alveoli and lungs. How? o Nose hairs: filter incoming air o Mucus: traps contaminants o Branches: block suspended mass from going down into lungs; will not be able to go around corners, so it gets stuck to the mucus o Cilia: move the mass to the pharynx, where it is deposited into the stomach Note: Mucus can remove things that are at least 4-6 microns so that they do not reach the alveoli. Cigarette smoke = 3/10 micron (reaches alveoli) Alveolar macrophages: cells that digest the particles that make it into the alveoli and take it to the mucus of the lymphatic system; do not cause inflammation o Smoking, alcohol consumption, and steroids can keep the macrophages from working o Smoking paralyzes the cilia, which keeps them from moving the mucus; it also stimulates more mucus secretion; smokers cannot properly clear mucus (hacking cough) Thoracic cavity There are no muscles of respiration in the lungs. The skeletal muscles outside the lungs make the thoracic cavity expand, causing respiration. A thin layer of serous fluid between the pleura keep the lungs from collapsing by keeping the lungs expanding and providing a layer of lubrication (keeps lungs attached to the thoracic wall) Pathologies: o Pneumothorax: a hole in the pleura that allows air into the thoracic cavity, which causes the lungs to collapse (e.g. stab wound) Traumatic pneumothorax: trauma causes a hole in the pleura (e.g. collisionrib through lung) o Open: penetrating wound through the pleura; sudden collapse from the hole, which allows air in and out o Closed: temporary hole which is closed off, only allowing some air to get in; partially collapses the lung

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o Tension: (check valve); one-way valve allowing air to come in when inhaling, but it cannot get out when exhaling; crushes the lung and causes lots of damage Spontaneous pneumothorax: sudden, unexpected collapse of the lung without external trauma; often there is a hole between the alveoli/bronchiole and the pleura (opening through visceral pleura from the inside) o Open, closed, or tension o Caused by: emphysema, pneumonia, tumor, or idiopathic (familial?) o Treatment for lung collapse: <20%: leave alone and air will be reabsorbed on its own >20%: thoracotomy: aspirate air out

Mechanisms of Respiration Internal respiration = cellular respiration External respiration = lung respiration Inhalation: volume increases and pressure decreases below atmospheric pressure, so that air flows into the lungs Exhalation: volume decreases and pressure increases above atmospheric pressure, so that air flows out of the lungs *Note: intrapleural pressure is always negative (-) because it is < atm. pressure Muscles used: o Inspiration: external intercostals (bring ribs up); diaphragm; scalene; sternocleidomastoids o Expiration: relaxation of inspiration muscles; internal intercostals (bring ribs down); rectus abdominus (flattens the stomach parallel to midline in the abdomen) Properties of the Lungs Elastic compliance: surface tension o Tissues and muscle measured by compliance o Compliance = V(volume)/P (pressure) o Compliance is good. o Compliance is reduced in patients with fibrosis, kyphosis, scoliosis, obesity, fibrotic pleurisy, and paralysis of the respiratory muscles. Non-elastic o Tissue resistance/viscosity o Resistance to change in shape (internal friction) o Airway resistance: resistance of air moving through the airway; similar to arterial friction o Airway resistance is found in patients with asthma, emphysema, and diphtheria.

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Note: Normally, the body uses 2-3% of total energy to supply breathing. If there is a problem, then even at rest the body uses up to 1/3 (33%) of the total energy to supply breathing. The workload caused by pulmonary disease can cause death. Tidal volume: amount of air you breathe in one breath (either in or out; not both) Respiratory minute volume: TV X Respiratory Rate; the volume breathed in/out per minute Alveolar ventilation: volume of fresh oxygenated air breathed in/out per minute Restrictive disorders: disorders caused by an increase in elastic resistance; quick, shallow breaths; found in pneumonia patients and in the obese Obstructive disorders: disorders caused by increased resistance in non-elastic resistance and TV; slow, deep breaths; lungs stretch normally, but there is trouble with movement of O2; found in emphysema and asthma patients Movement of gases in the alveoli Atmospheric pressure: 760 mmHg; mostly O2 and nitrogen o 21% O2; PO2 = 159.6 Alveolar partial pressure: O2, nitrogen, carbon dioxide, and water vapor o PO2 = 103 o PCO2 = 40 o Total pressure is the same as the atmospheric pressure (760 mmHg) Capillary lung partial pressures (dissolved in the blood) o PO2: venous end = 40; arterial end = 103 o PCO2: venous end = 46; arterial end = 40 Transport of O2 in the blood (Hb) 99% of O2 is carried on Hb; not part of PO2 of the blood There is a difference of environments from the lungs to the tissues. When PO2 falls in the blood, the Hb begins to let go of the O2. O2-Hb dissociation curve:

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o % saturated depends on the number of sites on the Hb that O2 is attached to Less saturation = less O2 attached o Hb changes color when O2 is released Red = 100% Blue/purple = 0% o PO2 100 means 100 % saturation o PO2 0 means 0% saturation o Sigmund curve o Why is it helpful? We can lose significant PO2 in the lungs and still oxygenate the body. o Less O2 in the atmosphere (e.g. mountains) = less P02, but you are still able to oxygenate the body o O2 is only delivered if PO2 is low enough to cause dissociation o If there is: pH temperature diphosphoglicerate (DPG) o Then: change in position on graph to the right o Caused by the production of lactic acid during exercise o More O2 is being delivered to the tissues o If there is: pH temperature DPG o Then: change in position on graph to the left o BAD o Alkalosis: increased pH CO2 + H2O + H2CO3 (carbonic acid) H + HCO3 (bicarbonate) o Respiratory alkalosis: not enough O2 in the atmosphere (decrease from the amount ones body is accustomed to) Increased bicarbonate; brain does not like it Leads to elevation sickness o S&S: dizziness, nausea, regurgitation, disorientation o Carbon monoxide: binds to Hb better than O2 does; fills the Hb slots in place of O2, making it unable to carry O2; death due to tissue hypoxia (slow) Transport of CO2 in the blood Some CO2 is dissolved in plasma (about 8% of the bodys CO2) Hb binds to CO2 when O2 is absent 65

o This is done about 25% of the time o CO2 + Hb HbCO2 (carbaminohemoglobin) CO2 +H2O H2CO3 (carbonic acid) H + HCO3 (bicarbonate) o As CO2 is exhaled, carbonic acid becomes CO2 + H2O This is done about 68% of the time Carbonic anhydrase: enzyme found in RBCs that makes this happen Note: CO2 levels are linked to bicarbonate levels.

Respiratory volumes and capacities

Reserve volume: o Inspiration reserve volume: amount of air inspired forcefully after inspiration of normal tidal volume; 3000 mL o Expiration reserve volume: amount of air expired forcefully after expiration of normal tidal volume; 1100 mL Residual volume: the air that does not leave the lungs after expiration; keeps the alveoli from collapsing; 1200 mL average Vital capacity: sum of inspiratory reserve volume + tidal volume + expiratory reserve volume; 4.8 L average Total lung capacity: sum of inspiratory reserve volume + expiratory reserve volume + tidal volume + residual volume; 5.8 L average Inspiratory capacity: sum of tidal volume + inspiratory reserve volume; total amount of air inhaled; 3500 mL average Functional residual capacity: sum of expiratory reserve volume + residual volume; amount of air left in the lungs from rest position tidal volume; 2300 mL average o Can be measured precisely o Will change with disease o Test:

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Nitrogen wash-out: Patient fully exhales and breathes pure O2; clinician catches all the air that is exhaled and measure the amount of nitrogen released Useful volumes: vital capacity (VC), total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV)

Respiratory Disorders Restrictive decreased TLC, FRC, and RV o Neuromuscular disorders of the rib cage o Anatomic disorders (e.g. kyphosis) o Diseases of the pleura and parenchyma Obstructive increased TLC, GRC, and RV o Trouble exhaling- slow, full breaths o Air is trapped in the lungs because the pressure on the alveoli closes off sections of the lungs. COPD (chronic obstructive pulmonary disease): asthma, chronic bronchitis, emphysema Blood gases o Include PCO2, PO2, and pH ([H+] ions) o Things to consider: CO Tissue perfusion Edema (created longer distances for diffusion) [Hb] and [hematocrit] o Hematocrit: % of blood that is RBCs o Polycythemia: above normal amounts of Hb o Anemia: below normal amounts of Hb CO2 + H2O H2CO3 (carbonic acid) H+ + HCO3 (bicarbonate) CO2 pH If you cannot breathe correctly, there are high amounts of bicarbonate and H+ ions, making the blood more acidic You must breathe at a rate that keeps the brains pH normal

pH HCO3 PCO2 Respiratory Acidosis * Respiratory Alkalosis * Metabolic Acidosis * Metabolic Alkalosis * *- Dr. Waldo believes that these started the problem & the other two scenarios are to compensate o Respiratory alkalosis: not common; altitude sickness and hysteria can cause it; leads to hyperventilation o Metabolic acidosis: hyperventilation o Metabolic alkalosis: hypoventilation (lack of breathing) 67

Pattern: o Respiratory acidosis and alkalosis have arrows opposite of pH o Metabolic acidosis and alkalosis have arrows facing the same way Dynamic lung volumes Respiratory minute volume (Ve): tidal volume (Vt) X respiratory rate in breaths per minute (F) o Note: V with a dot above (subscript e) = volume expired over time & F = frequency of respiratory rate Dead space: the space full of used air that remains in the lungs during inspiration; can no longer be used; 150 mL is average for a healthy male Alveolar ventilation: Va = F (Vt Vd); actual amount of useful fresh air breathed per minute *Vd = dead space volume e.g. F(500-150) = F(350) Vd/Vt ratio: the % of air that is dead space; measures efficiency of breathing (the larger the number, the less useful amount of air is breathed in); normally about .3 (30%); should not go > 30-40% (this means there is a pathology) Vt 250 500 1000 F 40 20 10 Ve (RMV) 10 10 10 Va (L/min) 4 7 8.5 Vd/Vt 60% 30% 15%

Vd A 150 B 150 C 150

Notes: o All patients are breathing in the same amount of air per minute o Patient A is breathing fast and shallow (60% of air is dead space) e.g. pleurisy o Patient B is breathing normally o Patient C is breathing slow and deep (15% of air is dead space) e.g. asthma Vital capacity: how much air can be breathed in or out? Forced vital capacity (FVC): force air out of the lungs as fast as possible; more air is trapped in the lungs, so FVC < VC Forced expiratory volume (FEV1): only count how much air you get out in one second; compare with FVC o FEV1/FVC ratio: % 80% for normal people and people with restrictive disorders <80% for patients with obstructive disorders

Proper exchange in the lungs must have: Ventilation: fresh air in the alveoli o V (with a dot on top) = alveolar ventilation Perfusion: blood flow to the alveoli 68

o Q (with a dot on top) = perfusion/CO o Normally, V/Q = .8 (80%) Dead space unit: Q=0; V/Q = infinity; no blood flow to alveoli Shunt unit: V=0; V/Q=0; no oxygen flow to alveoli Silent unit: V=0 and Q=0; no blood or oxygen flow to the alveoli V/Q > 0.8 = loss of perfusion V/Q < 0.8 = loss of ventilation Signs and symptoms of respiratory disorders Cough o Productive: phlegm and mucus are expelled o Hacking: short, frequent, feeble cough o Brassy: rattles the whole chest Sputum: excess mucus production expelled from the body o Yellow: infection; contains pus o Green: stagnant pus; neutrophils work on them, causing the mucus to turn green; indicated that mucus is not clearing from the chest; usually found in the morning & turns yellow during the day Hemoptysis: blood in the sputum; could become pure blood depending on the situation Dyspnea: difficulty breathing; real or perceived Chest pain: hurts to breath o Pleurisy: most common cause is inflamed pleura; sharp, cutting pain; breath shallow and rapidly Digital clubbing: clubbing of the finger tips; fingernails begin to angle down from normal (160) to about 180; drumstick appearance Cyanosis: skin takes on a bluish color; 5g% reduced Hb o Central cyanosis: insufficient oxygenation at the lungs; turn blue everywhere (lips, face, ear lobes, under tongue) o Peripheral cyanosis: insufficient oxygenation (blood flow) to certain area of the body; could be an obstruction, cardiac, insufficiency, being cold; unreliable sign Hypoxemia: low arterial PaO2 Hypoxia: low tissue PO2 o Can have hypoxia alone (localized); hypoxemia is always accompanied by hypoxia o The brain does not like either of these. o Symptoms: confusion, bizarre behavior, coma, increased respiratory rate, cyanosis, sweating Hypercapnia: arterial PCO2 > 44 mmHg; not enough breathing; can be due to anything that limits respiration (drugs, chest trauma, paralysis of chest muscles) o Symptoms: confusion, coma, asterixis (flapping tremor of the hands), warmth, sweaty extremities o Can switch to oxygen receptors (carotid artery) instead of the normal pH, but giving the patient pure oxygen can cause them to stop breathing (respiratory collapse) 69

Obstructive Respiratory Disorders Increase FRC and RV; difficulty exhaling COPD (chronic obstructive pulmonary disease): asthma, chronic bronchitis, emphysema o Asthma: shortness of breath S&S: increased mucus secretions, edema, bronchiospasms, decreased lumen size, panting o Extrinsic asthma: allergic asthma; most common in young children o Intrinsic asthma: idiopathic; usually comes after age 40; can lead to chronic bronchitis and emphysema o Mixed asthma: a combination of allergic and intrinsic asthma Treatment: bronchodilator, which desensitizes (builds up a tolerance from small exposure over time) o Chronic bronchitis: inflammation of the bronchi S&S: increased number of goblet cells increased mucus production, more inflammatory cells edema of mucosa, expectorant cough Difference from asthma: productive cough for 3 months out of the year for 3+ consecutive years Difference from emphysema: x-rays & elasticity of the lungs; associated with emphysema Primary cause: cigarettes; air pollution can cause o Emphysema: destruction of the alveolar sacs Panlobular emphysema: breakdown of alveolar sacs distal to the central bronchioles; outside in; rare, even distribution of damage; not associated with chronic bronchitis; equal percentage of cases in both sexes; genetic (familial); slow, insidious development Centrilobular emphysema: breakdown first in the respiratory bronchioles; inside out; men have it more often than women (due to percentage of men who smoke?); uneven distribution in the lungs Note: both types can be present in advanced cases 70

Bullae: expanded areas of alveoli with air trapped inside; eventually ruptures, causing air to enter the pleura o Bleb: air pocket inside bullae; puts air between the pleura, causing a spontaneous pneumothorax Atelectasis: total or partial collapse of the lung(s) Bronchiectasis: chronic dilation of bronchi; secondary to bacterial diseases (e.g. pneumonia, influenza, whooping cough, measles); can follow mechanical irritation (e.g. peanut falling into the lung) o Saccular: abnormal chamber; bubble; often happens at the 4th level of division in the lung o Cylindrical: larger than normal diameter of the bronchi; occurs deeper in the lung o S&S: large amounts of mucus, productive cough, petulant and foul-smelling sputum, changing position will change the ability of the body to expel mucus, hemoptysis, recurrent pneumonia, digital clubbing, cor pulmonale, shunting of the blood o Treatment: postural drainage (change the patient to the best position to expel the mucus), antibiotics, NO bronchodilators (bronchi are already dilated) Cystic fibrosis: genetic disorder (autosomal recessive) of the exocrine glands that affects 1/2000 Caucasians o S&S: salty sweat and saliva, thick and gooey mucus, fibrosis of pancreas (pancreas digestive enzymes become blocked so that food cannot be digested), lungs become blocked [inflammation, bacterial infections, Bronchiectasis], hypoxemia, cor pulmonale o 90% of deaths are caused by respiratory infections o Treatment: inspiratory mucus dissolving medications, postural drainage, beating on the patients back to break up mucus

Restrictive Respiratory Disorders Increase stiffness of lungs, decrease compliance, decrease lung volume (including VC) More work must be done to overcome elastic resistance Shallow, rapid breathing o Extrapulmonary Restrictive Disorders: restriction of the lungs caused by something other than the lungs themselves Neurological disease Barbiturates Head trauma- respiratory centers restricted 71

o Biots breathing: increased intracranial pressure (from head trauma) leads to cyclic breathing, which is 3-4 breaths followed by apnea Polio Amyotrophic lateral sclerosis Kyphosis Pectus excavatum: funnel chest; limits inspiration Rib fracture: causes pendelluft movement- movement of air back and forth between the lungs, causing increased dead space ventilation Ankylosing Spondylitis: chronic inflammation of the axial skeleton; causes pain when breathing because the joints between the ribs and vertebra are inflamed o Intrapulmonary Restrictive Disorders: restriction of the lungs caused by the lungs themselves Atelectasis: secondary to pathology; non-expansion of the lungs; collapsed alveoli; considered restrictive o S&S: dyspnea, cyanosis, tachycardia, chest pain, fever, mediastinum drifting to the collapsed side o Absorption Atelectasis: obstruction of airway; alveoli collapse over time and air is absorbed into the blood stream Blockage can cause intrinsic (mucus build-up) or extrinsic (tumor, enlarged lymph node) Note: Pore of Kohn that connects the alveoli is usually closed, but if a person takes a deep breath the pores will open. This allows air into the blocked alveoli. Therefore, if a person takes a deep breath they can bypass the blockage. Deep breathing exercises can help with this. Most often happens post-operative within 24-72 hours o Compression Atelectasis: external pressure closes the air passage; caused by pleural effusion, pneumothorax, abdominal distension (contents of the abdomen are pushed into the thoracic cavity) Pneumonia: acute inflammation of parenchyma of the lung o Frequency: 1% of the population per year; 8.5% of all hospitalizations; 3% of deaths o Bacterial pneumonia: accounts for 80-90% of all cases; usually caused by streptococcus or pneumococcus S&S: sudden onset, severe shaking chill, rapidly spiking fever, pleuritic pain (restrictive breathing pattern), productive cough with pinkish/rust-colored mucoid sputum, rales, friction rubs, hypoxemia, mild cyanosis 72

Treatment: antibiotics; mortality rate with treatment is 5-13%; resolution- exudates is broken down and reabsorbed; usually full recovery o Lobar pneumonia: involves the entire lobe; typical of pneumococcus and klebsiella o Lobular pneumonia: involves an area smaller than the entire lobe; lobulars are involved; exudates is primarily in the bronchioles; caused by staphylococcus and streptococcus o Interstitial pneumonia: inflammation of the interstitial space of tissue; edema between the alveoli; caused by viruses and mycoplasma; aka walking pneumonia Stop here for test #3.

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Test Four Kidneys Anatomy Nephrons Bowmans Capsule Glomerulus Loop of Henle Proximal & distal tubules Juxtaglomerular Apparatus

Notes 1 million nephrons per kidney (2 million per person) 20%-25% of cardiac output runs through the kidneys Types of nephrons: o Coritcal nephron: small loop of Henle does not run down into the renal pyramid o Juxtamedullay nephron: loop of Henle runs down into the renal pyramid Renal pyramids make up the medulla of the nephron The capillaries have holes in them, making it easy for blood to diffuse into the capsule Glomerular filtration: o Dilation of: Efferent arteriole = BP o filtration Afferent arteriole = BP o filtration o Constriction of: Efferent arteriole = BP o filtration Afferent arteriole = BP o filtration Aglomerular shunt: nephrons are destroyed, so blood is shunted from afferent to efferent arterioles without filtering out of the body 74

Amounts o 180 L (> 45 gallons) of plasma filtered per day o About 3 quarts of total blood plasma in the body o 1-2 L expelled from the body per day o About 99% is reabsorbed by the body o Tubular maximum capacity for glucose: (T max) the most glucose that can be reabsorbed in the proximal tubule to be sent back into the body; varies depending on what the substance is (e.g. proteins, lactic acid, carbohydrates) T max is about 325 mg/min Normal glucose is about 125 mg/min Sodium has an excessive t max Pathologies: o Diabetes mellitus: lack of or severe shortage of insulin production Insulin is required for the metabolism of glucose Blood glucose can reach levels of 500 mg/min Osmotic diuresis: H2O follows glucose out of the body; urine levels increase Glucose in urine does not necessarily mean the patient is diabetic. S&S: o Polyuria: frequent urination o Polydipsia: excessive thirst

Glucose moved (mg/min) vs. plasma glucose (mg/dL) or (mg%)

o Glomerulonephritis: inflammation of the glomerulus leading to leaking of protein into the urine (proteinuria) o Hematuria: blood in the urine (caused by severe glomerulonephritis) 75

Tmax for protein is very low. Normally 100% is reabsorbed, except for a protein called TammHorsefall, which is actively transported into the distal tubule Normally < 150 mg/day protein in the urine > 150 mg/day = pathology

Glomerular filtration rate o Nothing in the body can show us the exact filtration rate, so we use other equations to calucute it. o Inulin: not normally in the body; freely filtered substance put into the body (100% will be filtered) Amount of inulin filtered o PiCi (concentration X volume) o Pi: [inulin]plasma (amount injected) o Ci: volumeplasma (amount filtered) Amount of inulin in urine o UiV (concentration X volume) o Ui: [inulin]urine o V: volumeurine Combined equations o PiCi = UiV o Ci (GFR) = UiV/Pi Example: o Urine production (V) = 4.2 mL/min o [Inulin] in urine (Ui) = 600 mg/dL o [Inuline] in plasma (Pi) = 25 mg/dL o (600 mg/dL)(4.2 mL/min) / (25 mg/dL) = 100 mL/min GFR will change during kidney failure. Creatinine: closely related to inulin; freely filtered and can be secreted; can be used to calculate GFR Loop of Henle

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Isotonic: end of proximal tube Permeable to H2O: descending limb Impermeable: ascending limb; massive NaCl transport Hypotonic: beginning of distal tubule Collecting duct: H2O is diffused back into the body Know changes in concentration Antidiuretic hormone (ADH): released from the posterior pituitary gland; binds to receptors in the collecting duct that cause H2O to be reabsorbed; increases the permeability of HwO in collecting duct Supraoptic nucleus of the hypothalamus: measures the osmotic concentration of fluids in the surrounding cells o osmolarity (fluid concentration) of hypothalamus o (+) osmoreceptors o ADH release from posterior pituitary o H2O permeability of collecting duct o H2O reabsorption in body o urine output Pathologies: o Lesion of the pituitary gland: can keep ADH from being released, which causes a loss of H2O from the body and diluted urine o Diabetes insipidus: huge outflow of diluted, tasteless urine; ADH is not produced; approximately 25 L of urine output per day Note: Urine is basically sterile because there is very little filtering. The only bacteria comes from the urethra. o Inappropriate ADH Syndrome: excessive amounts of ADH (or a similar molecule) released; blood volume and blood pressure increase slightly because aldosterone system is shut down to keep the BP from increasing too much; decrease in Na+ reabsorption (increased loss of Na+ in the urine and a decrease of Na+ in the body) Normal [Na+]: 142 mEq/L Abnormal [Na+]: 110 mEq/L o Hyponatremia: [Na+] in the body o Action potentials would decrease o Paralysis o Coma o Sudden death o Kidney failure: loss of nephrons About 1/3 of normal amount of nephrons can maintain body functions As nephrons are lost, others hypertrophy (take in more filtrate) Flow rate can become 1000X normal, and nephrons lose ability to filter o Huge flow means inability to collect as many ions, so H2O follows the ions out of the body 77

o As kidneys fail, there can be increased urine production due to the kidneys losing control over reabsorption (up to 3X normal) Osmotic diuresis: increased [H2O] out of the body Concentrated

[Urine]/ specific gravity [Isotonic] of body

Diluted 2 million # of Nephrons 0

Lose ability to concentrate/dilute urine at all in end stage renal failure The fewer the neurons, the more isotonic the urine will be Distal tubule: controls final balance of urine ([Na+] and [K+]) as Na+ goes back into the body, and K+ goes out of the body Aldosterone can also control [Na+] and [K+] o [K+] o aldosterone release o K+ secreted into distal tubule o [K+] in body o [Na+] o aldosterone release o Na+ reabsorption at the distal tubule o [Na+] in body Kidney Failure o Caused by a severe decrease in the number of nephrons o Acidosis o Coma o Death o Hyperkalemia ( [K+]) o Inappropriate APs o Heart arrhythmias o Fibrillation o Other neuromuscular problems 78

o nitrogen-containing waste products Urea Uric acid Creatinine Acidosis (pH) o Acidic at both proximal and distal tubule; H+ pushed out of the body and NaHCO3- is pushed into the body; loss of nephrons = loss of ability to control pH [K+] o # of nephrons o # of APs o Fibrillations o Heart failure o Uncontrolled muscle contractions S&S (used to determine kidney failure) o Azotemia: [urea], [uric acid], and [creatinine] in body; usually caused by kidney failure o Blood urea nitrogen (BUN)/plasma creatinine (PC): increased amounts are indicative of kidney failure Normal BUN = 10-20 mg/dL Normal PC = 0.7-1.5 mg/dL Reasons for kidney failure: o Pyelonephritis: an infection of the kidney and the ureters (ducts that carry urine away from the kidney); disease of the kidney in areas other than the glomerulus o Glomerulonephritis: inflammation of the glomerulus Blockage of perfusion/blood flow Nephrosclerosis: sclerosis of the kidneys arteries Obstruction of the urinary tract Stages of kidney failure: o I: Decreased renal reserve: up to 75% loss of kidney mass; asymptomatic o II: Renal insufficiency: Filtration rate is above normal (>25%); loss of >75% of kidney mass Polyuria: urine Noct urea: inability to make it through the night without urinating Mild azotemia 79

o III: End stage renal failure: 10% or less of functioning neurons remain; urine output decreases Uremia: build-up of waste products in the body (nitrogen-based AND others) Isotonic urine: loss of ability to concentrate urine Specific gravity = 1.01 (locked) Oligurea: <500 mL/day of urine output Uremic Syndrome: this always happens in stage III renal failure o Graph: Blood urea nitrogen (BUN) and serum creatinine levels to GFR during the 3 stages of renal failure (key = normal protein intake, serum creatinine, low protein intake) o Low-protein diet delays azotemia o Secondary hyperthyroidism o Secondary hyperthyroidism: always happens in end stage renal failure (stage III) Parathyroid hormone (PTH) increases the [Ca++] in the blood Decreased Ca++ levels = release of PTH = Ca++ Increase of PO4 levels = release of PTH = PO4 To get Ca++ from the diet (gut), you must have vitamin D o Vitamin D (OH2)D3 (dihydroxy D3) in the kidneys o Kidney failure decreases [Ca++] in the body PTH (pulls Ca++ from bones blood [Ca++] blood [PO4] PTH does not stop because PO4 is still too high (The kidneys cannot get rid of it because they are failing.) and Ca++ is still being removed from the bones = PTH release o Crystallization in the body: lumps of calcium phosphate are deposited from the body ( in the eyes, joints, muscles, etc.) S&S (Uremic Syndrome) o Hyperthyroidism Weakened bones (especially in hips and ribs) because of reabsorption; teeth may fall out PO4 and Ca++ deposits in tissue o Kidney stones o Arthritis o Kerapotapy: calcium deposits across the eye Arterial sclerosis 80

o GI Nausea, vomiting, and diarrhea Anorexia- weight loss High urea levels in the blood and fluids Urine-smelling breath Bacteria in the mouth feed on urea and produce ammonia Ulceration and bleeding into gut o Neuromuscular Excitable AP Heart arrhythmias and fibrillations Apathetic mood Asterixis: muscle twitching or flapping of the hands Convulsions Coma o Cardiovascular Anemia (decreased amount of RBCs) Shortened RBS lifespan Hematocrit falls (30%) Dyspnea Coagulation defects Hypertension Heart failure Retinopathy o Genital/Urinary Pyruia: pus in the urine Hematuria Proteinuria Packing of nephrons with waste Women: lack of menstruation and loss of libido Men: impotent, sterile, and loss of libido o Skin Gray-yellow pallor of skin Uremic frost: urea comes out of the skin in sweat Pruritus: itching Easy bruising o Respiratory Hyperventilation Kussmaul respiration: deep sighing breaths Butterfly-shaped pulmonary edema Other kidney failure disorders o Nephrotic syndrome: Minimal change disease; massive proteinuria from a leaking glomerulus; basement membrane of the glomerulus is damaged

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Hypoalbuminemia: loss of osmotic pressure; massive body-wide edema; hyperlipidemia; lipiduria; decrease in circulating volume of blood ( H2O from body) o Causes: Primary kidney problem (e.g. glomerulonephritis) Metabolic disorders (e.g. diabetes) Hypersensitivity (e.g. lupus) Heart failure Toxins (e.g. mercury, bismuth, and gold) Allergens (e.g. snake bites, drugs reactions, poison ivy) Infections (e.g. TB, syphilis) o Nephritic syndrome: Acute proliferative glomerulonephritis (APGN) or Acute post-streptococcal glomerulonephritis (APSGN); follows strep infections and some viral infections (e.g. Measles, Mumps) Hematuria Decreased urine output Red cell casts Proteinuria Edema Hypertension (mild to severe) Azotemia Usually disappears, but potentially fatal Picture: Acute glomerulonephritis o Acute Pyelonephritis: Typically due to e-coli (fecal contamination) White cell casts Bacteriuria Burning on urination

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