Physio Midterm 4 essays - Theoretical Topics PDF

Preview

Summary

1. BLOOD -FUNCTIONS, PROPERTIES, COMPOSITION. BLOOD VOLUME. PLASMA –VOLUME, COMPOSITION.PLASMA PROTEINS – TYPES, FUNCTION.Blood Function: transport, regulatory and protectionBlood volume  8% of body weight Plasma volume  5% of body weightHematocrit: ratio of volume of RBC to total blood volume Mal...

Description

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

1. BLOOD -FUNCTIONS, PROPERTIES, COMPOSITION. BLOOD VOLUME. PLASMA –VOLUME, COMPOSITION. PLASMA PROTEINS – TYPES, FUNCTION. Blood Function: transport, regulatory and protection Blood volume  8% of body weight Plasma volume  5% of body weight Hematocrit: ratio of volume of RBC to total blood volume Males  0.40-0.54 Females  0.37-0.47 Plasma –55% of blood volume 90% H2O, 10% solutes (protein, nutrients, wastes etc.) Serum: plasma without clotting factors Plasma proteins Functions: colloid osmotic pressure, buffer, transport, regulation and protection Types 1. Albumin  60% of plasma proteins 2. Globulin  38% 3. Fibrinogen  2% –essential in blood clotting

2. RED BLOOD CELLS – COUNT, FUNCTIONS, LIFE SPAN. HEMOGLOBIN – FUNCTIONS, DEGRADATION, COMPOUNDS OF HEMOGLOBIN.

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

RBC Count: 4.5-6.0 x1012/L Life span - 120 days Main RBC functions are facilitating gas exchange: transport of O2 and removal of CO2, and regulating blood pH - RBCs facilitate gas exchange through a protein called hemoglobin Hemoglobin Each Hb molecule contains 4-iron binding heme groups which is the site of O2 binding - Binding affinity of O2 to Hb is cooperative: binding of an O2 molecule at one heme group increases the O2 affinity of the remaining heme groups in the same Hb molecule Types  HbA1 (22) is most abundant in adults  HbA2 (22): 2% in adults  HbF (22): major Hb found in the fetus and newborns Compounds of Hb  Oxyhemoglobin –HbO2 ~ 3ml O2 dissolved /litre plasma  Carbaminohemoglobin –HbCO2  Carboxyhemoglobin HbCO  Methemoglobin Fe3+ Degradation Hb  globin + heme Heme  porphyrin + Fe2+ Porphyrin is broken down into bilirubin (unconjugated) in the macrophages Unconjugated bilirubin is transported through the blood via albumin to the liver Bilirubin is conjugated with glucoronic acid within the liver Conjugated bilirubin is actively secreted into bile

3. PRODUCTION OF BLOOD CELLS - HEMATOPOIESIS. ROLE OF ERYTHROPOIETIN, VITAMIN B12, FOLIC ACID AND IRON IN ERYTHROPOIESIS. Hematopoieses: production of blood cells

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

Erythropoiesis –production of RBCs - Erythropoietin Leukopoiesis –production of WBCs - Cytokines Thrombopoiesis –production of platelets - Thrombopoietin All circulating blood cells are derived from pluripotential hemopoietic stem cells Growth and reproduction of various stem cells are controlled by multiple proteins called growth inducers and differentiation inducers Erythropoietin A glycoprotein hormone which stimulates erythropoiesis, 90% are produced in the kidney and 10% in liver Action of EPO: stimulates proliferation and differentiation of erythroid progenitor cells and protects cells from apoptosis Role of vitamin B12 and folic acid Both vitamin B12 and folic acid are essential to the synthesis of DNA Deficiency in either of these vitamins results in a reduced quantity of DNA and failure of nuclear maturation and division RBCs also become larger than normal (in addition to the inability to divide), developing into megaloblasts Cells have irregular shapes and flimsy cell membranes, capable of carrying oxygen normally, but fragility causes them to have a short life span Vitamin B12 or folic acid deficiency therefore causes maturation failure during process of erythropoiesis Iron Iron is important for the formation of hemoglobin, myoglobin, and other substances Transferrin: transport form of iron in plasma Transferrin is ingested via endocytosis into erythroblasts along with the bound iron Transferrin delivers iron directly to mitochondria where heme is synthesized Ferritin: protein complex which stores iron (intracellular), apoferritin is not combined with iron Hemosiderin: denatured and partially degraded ferritin, non-functional (iron is unavailable for cell) Anemia: deficiency of RBCs, caused by rapid loss or slow production

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

4. WHITE BLOOD CELLS (WBC). TYPES OF WBC. LIFE SPAN, PRODUCTION, FUNCTIONS. ROLE OF NEUTROPHILS AND MACROPHAGES IN INFLAMMATION. Leukocytes (white blood cells) are the mobile units of the protective system of the body Formed in the bone marrow and lymph tissue and transported in the blood to areas of inflammation to provide a rapid and potent defense against any infectious agent

Composition  Neutrophils: 60 - 70%, first line of defence  Eosinophils: 1 - 4%  Basophils: 0.5 -1%  Lymphocytes: 20 - 30%, life span is up to 300 days  Monocytes: 2 - 8%, life span is 72hr Granulocytes contain cytoplasmic granules that stain specifically (acidic, basic, both) and have lobed nuclei whereas agranulocytes lack visible cytoplasmic granules Role of neutrophils and macrophages in inflammation Inflammation –nonspecific response to a foreign invasion or tissue damage 1. First line of defence against invading organisms are tissue macrophages, they migrate to the area of inflammation and begin their phagocytic actions 2. Second line of defence are neutrophils, large numbers of neutrophils invade inflamed area as a result of the products in the inflamed tissue –attract these cells and cause chemotaxis toward that area 3. Third line of defence are monocytes, enter inflamed tissue from the blood and enlarge to become macrophages 4. Fourth line of defence is the greatly increased production of both granulocytes and monocytes by bone marrow Defence properties (A) Phagocytosis – most important function: engulf and digest foreign materials (B) Chemotaxis –WBCs are attracted toward inflamed tissue areas (C) Diapedesis –WBCs enter the tissue spaces (squeeze through pores of capillaries)

5. INNATE IMMUNITY. ADAPTIVE IMMUNITY. DEFENCE MECHANISMS IN ORAL CAVITY.

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

Innate immunity Refers to non specific defence mechanism that come into effect immediately, following the appearance of a foreign substance, it is activated by chemical properties of the antigen Non-specific response & defence: 1. Skin: physical barrier and chemical defence against chemical bodies 2. Cellular counterattack –WBCs circulate body and attack invading microbes Types:  Macrophages –major phagocytic cells, circulate continuously in extracellular fluid In response to infection, monocytes within blood enters the connective tissue and matures into macrophages at the site of infection 

Neutrophils –primary phagocytic cells, most numerous in body



NK cells –kill cells which have been infected with virus

Proteins of the complement system, may be activated to help attract phagocytes to foreign cells and destroy it. Process of coating a microbe’s surface with a molecule to enhance ingestion – opsonisation 3. Inflammatory response Infected/ injured cells release chemical signals –histamine Chemicals promote dilation of local blood vessels increase blood flow to site of infection and permeability of capillaries Adaptive immunity An individual gains immunity when they are exposed to a pathogen or foreign agent, it requires recognition of antigens, more complex and specific compared to innate immunity Individual develops immunological memory  re-exposure to antigen  quicker and more efficient Humoral immunity is mediated by antibodies produced by B lymphocytes When B cells are activated they divide, producing a clone of daughter B cells, these clones give rise to plasma B cells and memory cells - Plasma cell produce antibodies specific to the antigen and memory cells provide future immunity Role of humoral immunity is to protect the body from viruses, some bacteria and toxins which enter the body fluid like blood plasma and lymph Cellular immunity is mediated by T lymphocytes Activated T cells can proliferate and produce: 1. Th cells –signalling molecules are produced when endogenous Ag associated with MHC I are displayed on plasma membrane  Release interleukins which stimulate B cells to produce antibodies that can bind to antigens 2. Tc cells –cytotoxic molecules are produced when exogenous Ag associated with MHC II are displayed on plasma membrane  Secrete perforin which creates holes in the membrane of the target cell, this allows ‘granzymes’ (toxic molecules) to enter the cell Granzymes induce programmed cell death in target cell Oral defence system

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

Mucosal barrier –epithelial cells  antimicrobial proteins - Oral mucosa has Ag presenting dendritic cell Saliva possesses anti-microbial activity  IgA: most abundant Ig, limit microbial adherence and penetration of foreign Ag into the mucosa  Lysozymes: lyses bacteria  Proline-rich peptides and statherin binds to bacteria  Mucins entrap and aggregate microbial particles Tooth pellicle and dental plaque: bacteria and glycoproteins form a biofilm

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

6. EVENTS IN HEMOSTASIS. ROLE OF PLATELETS. Hemostasis means prevention of blood loss Stages of hemostasis: whenever a vessel is cut or ruptured, hemostasis is achieved through: (1) Vascular spasm (2) Formation of a platelet plug (3) Formation of a blood clot as a result of blood coagulation (4) Growth of fibrous tissue to close rupture permanently A. Trauma to blood vessel causes wall of the blood vessel to constrict, blood flow is restricted Endothelial surface is altered, collagen exposed Vasoconstriction results from nervous reflexes, local myogenic spasms, and local humoral factors released from traumatised tissue e.g. thromboxane A2, serotonin and endothelin B. Platelet plug can fill a small hole in a blood vessel When platelets come in contact with a damaged vascular surface, they begin to swell and adopt irregular form They release granules containing multiple factors, which increase the adherence of platelets –ADP, and form TxA2 ADP and TxA2 act on nearby platelets to activate them, they adhere to originally activated platelets forming a platelet plug C. Third mechanism for hemostasis is formation of blood clot Clot formation begins to develop within 15 -20 seconds if trauma to vascular wall is severe and within 1-2 minutes if trauma is minor Circulating soluble plasma protein (fibrinogen) is converted to insoluble strands of fibrin which form a mesh, trapping blood cells and preventing blood loss

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

7. MECHANISM OF BLOOD COAGULATION. PATHWAYS. Blood coagulation takes place in three essential steps: (a) Prothrombin activator is formed in response to rupture or damage to blood vessel (b) Prothrombin activator catalyzes conversion of prothrombin to thrombin (c) Thrombin acts as an enzyme to convert fibrinogen to fibrin Initiation of coagulation: prothrombin activator is formed in two ways: (1) Via the extrinsic pathway, begins with trauma to vascular wall and surrounding tissue, Extrinsic pathway 1. Traumatized tissue release tissue thromboplastin, TT These factors include phospholipids from the membranes of traumatized tissue and a lipoprotein complex that functions as a proteolytic enzyme 2. Lipoprotein complex of TT complexes with blood coagulation factor VII In the presence of tissue phospholipids and Ca2+ it enzymatically converts factor X to activated factor X 3. Activated factor X immediately forms a complex with tissue phospholipid (released as part of the TT) and with factor V to form a prothrombin activator Activated factor X is the protease that causes splitting of prothrombin to thrombin (2) Via the intrinsic pathway, begins in the blood itself 1. Through trauma, factor XII is activated to form a proteolytic enzyme: activated factor XII Blood trauma simultaneously damages blood platelets, which causes the release of platelet phospholipids, which contains a lipoprotein called platelet factor III –plays a role in subsequent clotting reactions. 2. Activated factor XII acts enzymatically to activate factor XI 3. Activated factor XI acts enzymatically to activate factor IX 4. Activated factor IX, along with factor VIII, platelet phospholipids and factor III activates factor X - If factor VIII or platelets are in short supply, this step is deficient Final step is the same as the extrinsic pathway Prothrombin Prothrombin is an unstable plasma protein that can easily split into smaller compounds, one of which is thrombin Produced continuously by liver, Vitamin K is required for normal activation of prothrombin  lack of vitamin K or presence of liver disease prevents normal prothrombin formation and results in bleeding tendencies Fibrinogen Fibrinogen is a protein formed in the liver, thrombin is an enzyme that acts on the fibrinogen molecule to form fibrin monomer Fibrin monomer molecule polymerizes with other fibrin monomer molecules to form long fibrin threads Fibrin-stabilizing factor is an enzyme which causes covalent bonding between the fibrin monomer molecules and adjacent fibrin threads,  strengthening the fibrin meshwork

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

8. INTRAVASCULAR ANTICOAGULANTS. LYSIS OF BLOOD CLOT. CONDITIONS THAT CAUSE EXCESSIVE BLEEDING, THROMBOEMBOLIC CONDITIONS. Anticoagulants  Tissue factor pathway inhibitor, TFPI is a mechanism which occurs during the initial phase of clotting Secreted by endothelial cells 

Activated protein C Thrombin-thrombomodulin complex activates protein C



Antithrombin Heparin increases the effect of antithrombin

Lysis of blood clot –fibrinolysis 1. Plasminogen is converted to plasmin by activators 2. Plasmin cleaves insoluble fibrin into soluble fibrin degradation products, FDP destroys factor V, VIII, XII 3. Plasmin is inactivated by inhibitors in circulation Activators Intrinsic: Factor XIIa, XIa Extrinsic: Tissue type plasminogen activator (t-PA), Urokinase type plasminogen activator (u-PA) Exogenous: Streptokinase, SK beta- streptococcus Control: Plasminogen activator-inhibitors: PAI-1 and 2) Plasmin inhibitors: α2-macroglobulin, α2-antiplasmin Bleeding disorders Failure of blood clot in response to appropriate stimulus results in spontaneous bleeding, usually systemic in nature can be fatal Causes:  Thrombocytopenia: low production or increased destruction of thrombocytes  Coagulation disorders: von Willebrand disease, haemophilia  Impaired synthesis of coagulation factors: vit K deficiency, liver dysfunction Thromboembolic conditions Inappropriate formation of clots in vascular system is known as thrombus  Stasis of blood (venous)  Increased production of procoagulation factors

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

9. RESPIRATORY SYSTEM – FUNCTIONS. MECHANICS OF PULMONARY VENTILATION. PRESSURES THAT CAUSE MOVEMENT OF AIR. RESPIRATORY MUSCLES. PULMONARY CIRCULATION. 10. LUNG COMPLIANCE, SURFACE TENSION, SURFACTANT. 11. MINUTE RESPIRATORY VOLUME. ALVEOLAR VENTILATION. EFFECT OF DEAD SPACE ON ALVEOLAR VENTILATION. F UNCTIONS OF THE RESPIRATORY AIRWAYS. CONTROL OF THE BRONCHIOLES. 12. GAS EXCHANGE. DIFFUSION OF GASSES, PRESSURE GRADIENTS. COMPOSITION OF ALVEOLAR AIR. DIFFUSION OF GASSES THROUGH THE RESPIRATORY MEMBRANE. 13. FACTORS THAT AFFECT THE RATE OF GAS DIFFUSION THROUGH THE RESPIRATORY MEMBRANE. DIFFUSING CAPACITY FOR OXYGEN. EFFECT OF THE VENTILATION-PERFUSION RATIO ON ALVEOLAR GAS CONCENTRATION - CONCEPT OF PHYSIOLOGIC SHUNT AND PHYSIOLOGIC DEAD SPACE. 14. TRANSPORT OF OXYGEN IN BLOOD AND TISSUE FLUIDS. ROLE OF HEMOGLOBIN IN OXYGEN TRANSPORT. OXYGEN-HEMOGLOBIN DISSOCIATION CURVES. FACTORS AFFECTING O2 CONTENT. 15. TRANSPORT OF CARBON DIOXIDE (CO2) IN THE BLOOD. DIFFUSION OF CO2. CHEMICAL FORMS FOR TRANSPORT OF CO2. CO2 DISSOCIATION CURVE. RESPIRATORY EXCHANGE RATIO.

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

16. REGULATION OF RESPIRATION. RESPIRATORY CENTER. FACTORS THAT AFFECT RESPIRATION. Respiration is controlled by nervous and chemical control Respiratory centre is located in the medulla  DRG (dorsal resp.group) –primarily concerned with inspiration  VRG (ventral resp. group) –neurons fire during both forced inspiration and expiration  Pre-Bötzinger area is where the rhythm is generated Centres in the pons:  Pneumotaxic centre, upper pons: inhibits inspiration –limits duration of inspiration  Apneustic centre, lower pons stimulates inspiration Neurogenesis: other neural contributions 1. Role of Reticular Activating System (RAS) Network of interneurons in brainstem Activity associated with "awake" state simulates respiratory ventilation, when RAS activity is reduced (sleep) ventilation is reduced 2. Hypothalamus: change in respiration associated with temperature regulation 3. Limbic system: respiratory changes in emotion, pain 4. Cerebral cortex: voluntary control of respiration (limited) 3 types receptors in the lung (1) Slowly adapting stretch receptors (SAR) Stimulus: distension of lungs  vagus nerve which inhibits inspiratory centre Found in the smooth muscles of the airways (trachea, bronchi) –mechanoreceptors (2) Rapidly adapting stretch receptors (RAR) Stimuli: mechanical and chemical irritation Afferent fibres in the epithelium of large airways (3) C- fibre afferents (unmyelinated fibres) Stimulus: harmful mechanical forces, substances released on tissue damage and inflammation In large airways, C-fibres form a nerve plexus beneath epithelium In the lung parenchyma C-fibres next to the capillaries

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

17. CHEMICAL CONTROL OF RESPIRATION. Most important factors affecting respiration are the levels of: O2, CO2, H+ in plasma and CSF, they are monitored by chemoreceptors Chemoreceptors (1) Central chemoreceptors are located at the ventral surface of the medulla: monitor [H+] of CSF, provided by CO2 CO2 + H2O  H+ + HCO3Most important receptor, mediates  70% of response Physiological significance of mechanism: it maintains PaCO2 within normal range (~ 40mmHg)helping maintain brain pH constant Increase in PCO2 stimulates ventilation whereas decrease depresses it

(2)

Peripheral chemoreceptors are located in the carotid bodies and aortic bodies: monitors arterial PO2, PCO2, pH Peripheral chemoreceptors are sensitive to low PaO2 (hypoxemia) Receptors responsiveness is enhanced by increase PaCO2 (hypercapnia) and  [H+] (acidemia) in the arterial blood

18. ENDOCRINE SYSTEM - FUNCTIONS. TYPES OF HORMONES – CHARACTERISTICS AND PHYSIOLOGIC EFFECTS. MECHANISMS OF HORMONE ACTION. CONTROL OF HORMONE SECRETION. Overall function Regulates

BLOOD. RESPIRATORY SYSTEM. ENDOCRINE PHYSIOLOGY.

      

Growth, metabolism, tissue maturation Reproductive function Water and electrolyte balance Blood glucose Heart rate and blood pressure Immune function Milk secretion

Types of hormones  Steroids derives from cholesterol; lipophilic Secreted by adrenal cortex, placenta and gonads 

Non-steroid, water-soluble (hydrophilic) Peptides, proteins, glycoproteins Amino acid derivatives (amine hormones):  Derivatives of tyrosine (A, NA, dopamine) or tryptophan (melatonin) –hydrophilic  Thyroid hormones derivatives of tyrosine –lipophilic

Mechanism of action Hydrophilic hormones e.g. peptides cannot cross the targets cell membrane they bind with membrane receptor which initiates signal transduction processes (secondary messenger system) E.g. G-protein coupled receptor, cAMP Steroid hormones Most steroid hormones are bound to plasma protein carriers, only free steroid hormones can diffuse into target cell Steroid hormone receptors are typically in nucleus or cytoplasm - Some can bind to membrane-bound receptors that use second messenger system Receptor-hormone complex binds to DNA and activates or represses one or more genes Activated genes create new mRNA that moves into cytoplasm Translation produces new proteins for cell processes Control of hormone secretion a. Humoral stimulus Low blood concentration of Ca2+ stimulates secretion of PTH from parathyroid glands b. Neural stimulus Preganglionic sympathetic fibres stimulate adrenal ...