All physio 2 notes PDF

Preview

Summary

Midterm 1:Lecture 1: C10 Blood and immune systemBloodo ComponentsOnly fluid connective tissue in bodyErythrocytes RBC ( 45 %) leukocyte platelets ( 1 %) in plasma ( 55 %)o Physical characteristicsColor = scarlet O2 rich dark red O2 poorMore viscous then waterPh 7.35-7 / temp 38 C8% of body we...

Description

Midterm 1: Lecture 1: C10 Blood and immune system  Blood o Components  Only fluid connective tissue in body  Erythrocytes RBC (45%) leukocyte platelets (1%) in plasma (55%) o Physical characteristics  Color = scarlet O2 rich dark red O2 poor  More viscous then water  Ph 7.35-7.45 / temp 38 C  8% of body weight 5.5L men 5L women o Functions  Transport  O2 from lungs and nutrients from GI tract to cells  Metabolic waste from cells to kidneys and lungs  Hormones to target organs  Regulation  Temp / distribution / conservation / dissipation  pH in body tissue (plasma proteins, bicarb)  CO2 + H20 --> H2CO3 --> H + HCO3  Adequate fluid volume  Protection  Platelets / plasma proteins / blood clotting  Antibodies complement WBC o Blood plasma (55%)  General  Straw colored 91.5 water and 8.5 solutes (proteins)  Plasma proteins confined to blood made by liver 6-8% weight  Albumin 54%  Non specific carrier of molecules important blood buffer  Major osmotic protein (Na = major ion)  Globulin 38%  Immunity A & B globulins (highly specific but poor water solubility)  Gamma = (immunoglobulin)  Alpha = (Angiotensinogen ) (clotting)  Fibrinogen 7%  Precursor to fibrin  Blood coagulation  Difference between plasma and serum???  Plasma = has fibrinogens (want to prevent clotting)  Serum = no fibrinogens (NO CLOTTING FACTORS) o Formed elements (Erythrocytes / leucocyte / platelets) (45% of whole blood)  Why only leukocytes are complete cells?  Have nucleus and all components of cells (organelles)  General  Most FE are short lived and disposable (replaced by bone marrow)  Hematocrit = % total blood vol occupied by RBC (45 men 42 women)



   o 







Testosterone  Stim erythropoietin (EPO) synthesis by kidneys Anaemia  Low hematocrit 30% Polycythemia  High hematocrit 70% Blood doping (Epoetin Alfa)  Increasing EPO to increase RBC Erythrocytes (RBC) 45% Properties  8um diameter 1-2um thick biconcave (NO NUCLEUS or organelle)  Spectrin = maintain biconcave shape allow deformity (WHEN?)(capill) Specialized RBC characteristics  Small size biconcave shape  280m Hb molecules / RBC  Generate ATP anaerobically Hemoglobin Hb  Binds  O2 / CO2 / H+ / CO (200x affinity O2 depriv) / NO  Binding is reversible  Properties  Protein globin bound to 4 red heme pigment (Bind O)  Globin = 4 polypeptide chains 2a+2B each chain wrapped around central heme group  General  NOT lost through capillary membranes and doesn’t contribute directly to osmotic pressure and viscosity  O2 binds heme (Fe core) and CO2 with globin Erythropoiesis  General  Hemocytoblast -> Proerythoblast -> Reticulocyte -> Erythrocytes  Occurs in red bone marrow (network of reticular CT + wide cap)  Reticulocytes migrate through thin cap walls to blood  Haematopoiesis  Formation of any FE (RBC/WBC)  Haematopoietic stem cells (hemocytoblast)  Stem cells for all FE  Reticulocytes  Possess organelle unlike erythrocytes  Being to transport O2 mature erythrocytes after 24H  Normally 0.5-1.5% of total RBC  Above 1.5 indicates = activation of Erythropoiesis  Regulation  Balance between prod and destruction  Too many = polycythemia  Too few = anemia  Rate

 

action Pernicious anemia  Deficiency in B12 (low intrinsic factor from stomach) Erythropoietin (EPO)  General  Glycoprotein hormone prod in kidneys (main) and liver  Always some EPO in blood additional release due to hypoxia  Kidneys sense O2 delivery -> takes couple days for response  Causes hypoxia  Hemorrhage / RBC destruction  High altitude pneumonia  Increased demand (aerobic exercise)  Prevention of EPO  Excess RBC  Renal failure patients  Lack of EPO (RBC count can be 50% normal)  Use recomb EPO to cure  Athletes and EPO abuse  Can increase hematocrit (45 to 65%) but increases viscosity  Dehydration during race can clot / stroke / heart fail Destruction of erythrocytes (macrophage)  Mature ones cannot synth proteins grow or divide  Life span of 120 days  Spleen = RBC grave  Iron store/reused in liver  Heme degraded to bilirubin for excretion urine  Globin recycled for AA Disorders Anemia's  Symptoms  Low hematocrit erythrocytes 30% instead of 45%  Tired pale short breath chilly  Types  Nutritional = Fe deficit / low diet B12  Pernicious = lack of intrinsic factor from stom (Low B12)  Aplastic = bone marrow has basic needs but cannot make  RBC (stem cells damaged)  Renal = diseased kidneys deficient in EPO  Haemorrhagic = can be reversed quickly  Hemolytic = sickle cell / malaria RC rupture prematurely  Sickle cell anemia  General 





 

2mill/second if iron + Vit B present Folic acid for thymine synth and Vit B12 for folic acid

  

o 







Point mutation affecting one AA Effect

Hemoglobin structure deformed so low oxygen transp  Sickle cell anemia vs sickle cell trait  Can be hetero so only half RBC are sickles  This gives the malaria resistance TRAIT  Persists in certain part of world  Increased res to malaria keeps this trait  Polycythemia  General  Excess RBC hematocrit  Dehydration (relative poly) due to lower fluid not really higher RBC  Types  Primary (vera)  Cancer of bone marrow increasing RBC count  Secondary  Climber at high altitude increasing EPO to get O2  Artificial  Athlete that takes EPO to increase RBC Leukocytes WBC General  Amoeboid  Only FE that are complete cells have nucleus and all organelle  Diapedesis (leaving capillary)  Positive chemotaxis (chem trail) Polymorphonuclear granulocytes (NEB)  General  Sphere larger then RBC w/ lobed nuclei  Cytoplasmic granules for wrights stain (met blue + eosin)  Neutrophils



Half of WBC cytoplasm has 2 types of granules (acidic/basic dyes)

 





  



 

  

Granules contain hydrolytic enzymes & Anti-Biotic defensins Phagocytes ingest and destroy bacteria (meningitis) Eosinophils  2 lobe nucleus + red granules  Most important against parasitic worms (surround release enz)  Reduce severity of allergies by phagocytosis of immune complex Basophils  Rarest WBC cytoplasmic granules contain histamine heparin  Serotonin intensifies inflamm response S/U shaped nucleus Mononuclear agranulocytes (LM) General  No visible granules nuclei spherical or kidney shaped Lymphocytes  2nd most common WBC large purple nucleus + rim of pale blue cytoplasm  Most in lymphoid tissue some in blood  (T)hymus cells = act directly against virus cells tumor cells  (B)oneMarrow cells = give rise to plasma cells that prod AntiBod Monocytes  Largest lots of gray-blue cyto + dark nucleus U or kidney shaped  Differentiate into macrophages inside tissue  Phagocytic in chronic infections  Important against virus and intracellular bacterial parasites Production and lifespan of leukocytes Leucopoiesis is hormonally stimulated colony stim factors  Made by macrophage and T lymphocytes  1.3x10^6 WBC / second Bone marrow stores mature granulocytes (10-20x > blood) Life span of granulocyte = 0.5-9 days Stem cells

Committed cells Products

 

Hemocytoblast Myeloid SC

Lymphoid SC

Myeloblast Monoblast

lymphoblast

Eosinophil Monocyte Lymphocyte Neutrophil Into Basophil Platelets Leukocyte disorder Leukemia  Cancer of WBC  Descendants of single cell remain unspecialized and mitotic

  

o

o

Acute = from blasts / Chronic = from later states Lots of non functional WBC Symptoms  Internal bleeding and overwhelming infection  Acute  Bone marrow taken over by cancer  Severe anemia + clotting issue  Infectious mononucleosis  Epstein barr virus  Deformed Excessive agranulocyte  Leukopenia  Low WBC due to drugs (glucocorticoids) or anticancer agent Practice question  D / C / B / 120 days cant replace protein so get stuck due to lack of plasticity Platelets  General  Cytoplasmic fragment of megakaryocytes that are anucleate  10 day life span  Granules contain factors and enzymes involved in blood clotting  Regulated by hormone thrombopoietin in liver  PM network divides cytoplasm into compartments  Megakaryocytes break into thrombocyte  Hemostasis (clotting)  Quick Localized response to damage that is carefully controlled  3 phases 1. Vascular spasm  Vasoconstriction of vessel when damaged (Smooth muscle)  Allows time for plug to form 2. Platelet plug formation (s32)  2 types of granules are within platelet  Alpha  Have clotting factor + PDGF  Proliferation of vascular endothelial cells SM and fibroblast to repair damage  Dense  ADP / ATP / Ca / Serotonin  Enzymes to make thromboxane A  PG that stim release of ADP / serotonin  Fibrin stabilizing factor  Steps  Exposure to collagen stim swelling of platelets & become spiky and sticky  Adheres to collagen ---> Degranulation  Release of ADP and Thr.A activating more platelets  Sero and Thr.A induce vasocon + Spasm + Aggreg  ADP promotes platelet aggregation + degranulation  Plug anchored by fibrin threads

3.











Blood clotting (coagulation)  Blood transformed liquid to gel  3 stages  Prothrombin activator (factor X) formed  Factor X converts prothrombin to thrombin  Thrombin catalyzes joining of fibrinogen --> mesh 2 paths TO prothrombin activator (Factor X) (just know paths) 1. Intrinsic path (7 steps)  Slower  Trigger = damage INSIDE vascular system  All comp within blood system (NO OUTSIDE DMG)  Blood clotting inside vessel  Begins at Hageman factor (XII) + exposed collagen 2. Extrinsic path (4 steps)  Faster  Trigger = Damage OUTSIDE vascular system  Clotting in response to trauma injury  Tissue releases tissue thromboplastin (activates X)  Bypasses intrinsic path steps 3. Prothrombin act is rate limiting step  Once achieved clot form takes 10-15 seconds Clot retraction and repair 1. General  Happens in 30-60 min  Platelets contract (actomyosin) Pulls fibrin strands  Serum squeezed from clot and ruptured edges of BV pull in 2. PDGF (platelet release rxn)  Stim smooth muscle and fibroblasts to divide rebuild wall  Endothel cells multiply to fill gap Vitamin K in clotting 1. Needed for synth of 4 clotting factors ((PThr = II, VII, IX, X) by hepatocytes 2. Liver helps abs Vitamin K through bile salts in bile Fibrinolysis 1. Removal of fibrin clot when not needed 2. Key breakdown enzyme is plasmin 3. Plasminogen activated by tPA (tissue plasminogen act) by endothelial cells 4. Begins within 2 days Factors limiting clot growth/formation 1. Clot form needs procoag factors > anti-coag factors 2. 2 homeostatic mechanism  Swift removal of coagulation factors  Inhibition of activated clotting factors 3. NO and Prostacyclin (PGI2)  Released by healthy endothel cells inhibit platelet aggreg where there is no need for clots limiting to area of dmg 4. TFPI (tissue factor path inhib)





 Released by healthy endothel cells  Binds to Thromboplastin blocking prod of Factor X 5. Thrombin (+ve FB)  Can bind to endothel receptors thrombomodulin and neutralize thrombin clot forming ability  Can ACTIVATE and LIMIT clot form/size  Procoagulant  Cleaves fibrinogen to fibrin  Activates clot factors  Stim platelet activation  Anticoagulant  Activate protein C inactivating clotting factors 6. Antithrombin III  Inactivates thrombin and other clotting factors  Intravascular clotting 1. Thrombus  Clot that forms in unbroken blood vessel  Cause = High BP / Slow flowing blood (long stasis) 2. Embolus  A Free floating thrombus (air/bubble/debris) Drugs for clotting  Anticoagulant medication  Aspirin 1. Blocks Thr.A production  Heparin 1. Hemodialysis open heart surgery activates Antithrombin III  Warfarin 1. Antagonist to Vit K slower then heparin  Ca chelators 1. CPD (citrate phosphate dextrose) for donated blood to prev clot  Thrombolytic agents  General 1. Dissolve clots direct/indirect activate plasminogen  Streptokinase 1. From bacteria  Tissue plasminogen act (tPA) 1. Genetically engineered clots associated with MI and strokes

Blood groups and types o Antigens (agglutinogens)  Genetically determined cell surface glycoproteins and glycolipids  24 blood groups >100 antigens  2 major blood groups are ABO and Rh o ABO blood group system  Based on 2 glycolipid antigens A and B ( A / B / AB / O )  Plasma contains antibodies (agglutinins) (Anti-A and Anti-B)  Blood type A  Antigen A / Anti B



Blood type AB Antigen A and B / No antibodies  Blood type O  No antigen / Has both antibodies Universal donor = Type O (No antigens) Universal acceptor = type AB (No antibodies) Most common  Usually O A B AB is the order  Rh+ almost always Rh blood group Rh antigen first found in rhesus monkeys (Rh) Rh+ antibodies NOT spontaneously formed in Rh (-VE)  Becomes sensitized with first exposure (+ve baby makes mom +ve Anti)  Next pregnancy of Rh- moms Rh+ AB will attack child AB will attack Rh+ RBC with additional exposure Treatment with RhoGAM to prevent hemolytic disease of newborns  Accel phago of RBC before they can activate immune system New born blood No ABO antibodies  Begins to form 2 months and peaks at 8-10 years  Transfusion of incompatible blood can be fatal  Only ABO and Rh antigen cause serious agglutination problems Transfusion reactions Problem = recipient antibodies not donors  Agglutination clogs small BV  Clumped RBC rupture Hb released Autologous transfusions  1unit/4 days upto 3 days before surgery Blood typing Serum containing anti-A or anti-B agglutinins Similar procedure for Rh factor typing 

  

o  

  o 

o 

 o  

Lecture 2: Blood and immune system (Ch11)  Innate defenses (non specific) o General  Protect against foreign sub/abnormal cells WITHOUT having to specifically ID  General Carb/lipid surface markers bind to Toll like receptors TLR on macro phage cells o External defenses (Skin/mucus membrane) (1st line)  Physical barriers  Effective but can be breached  Bactericidal chemicals  Skin acidity / urine / vag sec / sebum  Gastric HCl  Saliva and lacrimal fluid has lysozymes (destroy bacterial cell walls)  Mucus Elevator  Mucus in respiratory and digestive passages



Immune protective functions of skin General  Significant physical barrier  SALT (skin associated lymphoid tissue)  Langerhans cells (dendritic cell)  Antigen presenters  Mobile sentinels travel to present antigen to T cells  Lymphatic system to present them to T cells in lymph nodes  Sebum  Released into hair follicles contain some broad spectrum antibac  Sweat  Has Dermcidin and usually acidic pH Inflammation General  Response to any type of injury  Occurs as part of non specific defenses and can be amplified by specific immune sys  Inflammatory chemicals released by injured cells macrophages/lympho 4 key signs  Redness heat swelling and pain  Vasodilation oedema Reasons  Iso area and prevent spread of damage agents to tissue  Dispose of cell debris and pathogens  Sets stage for repair process Steps  Break in skin allows bacteria in  Macrophages engulf pathogen and secrete cytokines and chemotaxins  Mast cells release histamine  Histamine dilates BV  Chemotaxins attract neutro/mono that diapedesis and go to inf site  Mono enlarge into macro and neutro engulf/destroy pathogen Interferons General  Virus rely on protein synth machines of host for reproduction  Secreted by virus-infected cells and diffuse to non-infected cells and block protein synth at level of ribosomes  NOT virus specific  Activates macrophages and mobilize NK cells = anti-cancer Steps  Virus enters and replicates --- cell releases interferons  Interferon binds with receptor in healthy cell  Healthy cell makes inactive enz to break down viral mRNA and inhibit protein synth  Virus blocking enzymes activated and thus cant multiply 

o 







o 



o 

 





o    

o 



 Further virus that enters "protected cells" cannot multiply Complement General  Group of 30 plasma proteins in an inactive state  Activated = amplification of all aspects of inflammation  Can kill bacteria and certain cells on its own  Extracellular killing (fluid in an burst)  2 paths to C3 --> Common terminal path causes cell lysis (HOLE/MAC) Opsonin (C3b)  Coating of bacteria to make it more susceptible for phago MAC formation C3  C3 -> C3b (phago) + C3a (inflam) --> C5 -> C5a (mast histamine) C5b --> C6/7/8/9 ----> MAC Paths for activation of C3  Innate system  Carb complex on microbes (NO ID OF WHAT BACTERIA)  Adaptive (Classical)  Antibodies produced against that SPECIFIC invader Functions of complement proteins  Direct destruction by MAC (mem attack comp)  Vasodilation and higher perm of capill/veins to proteins  Chemotaxis  Enhanced phagocytosis (opsonization) Fever Bodies thermostat normally 37C Reset by pyrogen released by leukocytes and macrophage exposed to bacteria and other foreign substances High fever is dangerous  If temp get too high proteins denature Moderate fever helpful  Speeds metabolic rate  Cause liver/spleen to sequester iron/Zn Natural killer cells (NK) General  Type of lymphocyte NOT specific to particular antigen  Part of innate immune system  Additional support for adaptive immune system  Attacks virus-infected or cancer cells without recog of antigen  Recogs cells that are stressed (NO MHC)  Activation not understood  MHC proteins not involved  Can recognize any harmful cells that DONT have MHC1 MHC molecule  Strong inhibitor  Healthy cells have enough MHC to inhibit NK cells  Reduced inhibitor  Tumor/virus cells have low MHC so NK attacks  Strong activators





Transformed/infected cells have molecules that are recognized by NK cells and allows NK attack even if MHC present

Adaptive (specific) defenses o General  Acquired immunity  Sub pop of lymphocyte recog and attack specific target o 3 types  B lymphocytes (humoral/AB immunity)  T lymphocytes (cell med immunity)  Macrophages (antigen presenting cells) o Lymphocytes  Originate in red bone marrow from hemocytoblasts  Initially all lymphocytes identical B vs T refers to site of immunocompetence o Antigen  Substance that is recog as foreign by immune system o Major histocompatibility complex (MHC)  Group of cell surface glycoproteins that mark cell as SAFE o T cells  Migrate to Thymus and matures (2-3days) through thymic hormones  Positive selection  T cells MUST recog Self MHC  Failure to recog MHC = apoptosis  Recog MHC = MHC restriction (proceed to negative selection)  Negative selection  T Cell must NOT recog Self Antigen  Recog self antigen = apoptosis to elim reactive T cells (autoimmune)  Fail to recog self antigen = survival of T cell o B cells  Immature lymph mature in BM and self reactive ones removed  Once immunocompetent  Unique receptors on surface make them able to react to ONE AND ONLY ONE foreign antigen  Lymph become IC before meeting antigen may later attack o Humoral/Antibody mediated immunity  General  Antigen challenge usually in spleen or lymph node  If lymph is a B-cell ----> humoral response is evoked  Plasma cells create specific antibodies (last 4-5 days)  Antibodies circulate and bind free antigens marking for destruction  Remaining cells become memory B cells  Path  Invader with antigens bind SPECIFIC B cell anti-body  Specific B-cell self clone into Plasma and memory B cells  Plasma cells secrete antibodies SPECIFIC to that invader  B-Cell presents APC on MHC 2  Antibodies



Structure Y shaped Heavy chain and light chain 2 ...