Anatomy Physiology Bio 2402 Lecture

1. Anatomy & PhysiologyBio 2402 Lecture Instructor: Daryl Beatty Day 3 Class 3 The Heart, Cardiac Muscles & Rythym

2. Review: Look back at Clotting and control of clotting

3. Blood Disorders Disorders of the Erythrocytes Polycythemia Anemia

4. Anemias � Symptoms Lethargy Loss of stamina & energy �Winded� � rapid respiration Pallor Depressed metabolic rate Anemia is a symptom What is a sign or a symptom? Sign is visible, symptom is something you can feel. Anemia is a symptom What is a sign or a symptom? Sign is visible, symptom is something you can feel.

5. Anemias � Types (655) Hemorrhagic � internal bleeding Hemolytic anemia � erythrocytes rupture prematurely Aplastic anemia � Red marrow not functioning, (drugs, radiation, virus,) - It also results in loss of immunity and clotting. - Treatment with cord blood or bone marrow transplant What is difference between hemorrhagic or hemolyticWhat is difference between hemorrhagic or hemolytic

6. Polycythemia Excessive levels of RBC�s Polycythemia Vera � Type of Bone Marrow cancer Count may be 8-11 M vs. 4-5 M cells/ ul Hematocrit may reach 80% Blood volume may double Treated � remove blood and replace with saline

7. Polycythemia Excessive levels of RBC�s Secondary Polycythemia � 6-8 M RBC�s/ul commonly those living at high altitudes.

8. Hemostasis � Three steps(663) Vascular Spasm � Step 1 What is a muscle spasm? Structure of the vessel? Smooth muscle in wall Reaction to injury � spasm Reduces diameter Cuts flow almost instantly

9. Hemostasis � Step 2 Platelet Plug Formation � Step 2 (665) Smooth vessel walls do not attract platelets (Blood vessels & platelets both + charged) Rough surfaces cause platelet adhesion Once attracted, they release serotonin (enhance the vascular spasm) Also, ADP, Thromboxane A (prostaglandin) Within one minute this occurs Platelet plug will stop very minor �leaks� If a severe cut, we move to step 3.

10. Hemostasis � Step 3 Coagulation � Page 664 Very complex � about 30 substances Good illustration of irreducible complexity 13 clotting factors � most from liver About 30 total chemicals

11. Coagulation -Two triggers Intrinsic Extrinsic

12. Hemostasis � Summary Coagulation � Page 664 Very complex � about 30 substances 13 clotting factors � most from liver About 30 total chemicals Illustration of irreducible complexity Contrast to adaptation of sickle cell to P.falciparum (Malaria).

13. Hemostasis � Clinical Application Drugs may interfere with clotting (can be good or bad) Aspirin � Often recommended for those over 50, reduces stickiness of platelets. Coumadin � Maintenance for those prone to clotting � and in atrial fibrillation Plavix � Newer � maintenance drug Heparin � Used in IV lines and blood collection Typically suspend these before surgery

14. Hemostasis � Clinical Application Larger cuts stimulate faster clotting Major arterial bleeding has too much pressure for clotting (aneurisms and trauma lethal)

15. Bleeding Disorders (667-8) Thromboembolic Conditions (Defined as formation of undesired clots) Thrombus � (Stationary clot) � obstructing flow strokes, heart attacks, DVT�s Atheroschlerosis � �plaque deposits� Embolus � portion of a thrombus which has broken free into the blood flow, (or any other material that can obstruct flow.) Plaque tends to stimulate platelet activity, and cascade the clotting response. Plaque especially dangerous when it becomes inflammed. Plaque tends to stimulate platelet activity, and cascade the clotting response. Plaque especially dangerous when it becomes inflammed.

16. Bleeding Disorders (667-8) Thromboembolic Conditions TYPES: DIC � Disseminated intravascular coagulation Plaque tends to stimulate platelet activity, and cascade the clotting response. Plaque especially dangerous when it becomes inflammed. Plaque tends to stimulate platelet activity, and cascade the clotting response. Plaque especially dangerous when it becomes inflammed.

17. Bleeding Disorders (667-8) Thromboembolic Conditions Thrombocytopenia � (668) Spontaneous bleeding � widespread Caused by bone marrow suppression Sign - Platelet count of <50,000/ul Platelet transfusions for temporary relief.

18. Bleeding Disorders (667-8) Hemophilia Hemophilia A � most common Genetic & expressed mainly in males Hemophilia C � less common, both sexes Symptoms � joints debilitated, bleeding, bruising Genetic defect of clotting factor. Treatment � Plasma transfusions, Synthetic factors now available.

19. Bleeding Disorders (667-8) Role of impaired liver function Synthesizes the pro-coagulants Also produces bile Bile is important in fat absorption Vitamin K from bacteria is fat soluble, and hence hard to absorb with poor fat digestion.

20. Steps in Healing 1. Clot retraction Platelets contain contractile proteins (Actin & Myosin) and growth factors for vessel repair Begins rapidly � within about 1 hour Review � Primary & Secondary Unions

21. Steps in Healing 2. Fibrinolysis (Pg 666) Define Fibrinolysis - Breaking up the clot Plasminogen is in the clot � (inactive form) Plasmin is a protein digesting enzyme TPA � Tissue Plasminogen Activator released about 2 days later from the cells of the endothelium of the vessel.

22. Clinical Application TPA � Tissue Plasminogen Activator Clinical Application: TPA also used in ischemic strokes and some heart attacks Must be given in first 4 hours What happens if TPA given in hemorrhagic stroke?

23. Undesired Clotting Why would plaque initiate clotting?

24. Factors Limiting Clot Formation Homeostasis Removal of clotting factors � quickly (concentration away from site) Inhibition of clotting factors � must reach a critical concentration to trigger the sequence.

25. Factors Limiting Clot Formation Platelet charge (+) repels vessel wall Natural Anticoagulants � Antithrombin III � prevents Thrombin activity Prostacyclin � inhibits platelets from sticking Heparin- from endothelium and Basophils & masts Vitamin E � Inhibits platelets � (but some studies have not shown it to reduce heart attacks, as aspirin will).

26. Factors Limiting Clot Formation - Application Blood flow prevents coagulation DVT � Deep vein Thrombosis from �sitting� Blood transfusion & Storage Citrate or oxalate is used to bind Ca++. Heparin is used in IV lines. -

27. Review of Cardiac Blood Flow Be able to trace flow, from start to finish Questions: How do the valves work Name the parts & vessels Questions: How do the valves work Name the parts & vessels

28. Review of Cardiac Blood Flow Pulmonary & Systemic Circuits Thickness of each chamber (also pg 685 TR) Why? Questions: How do the valves work Name the parts & vessels Questions: How do the valves work Name the parts & vessels

29. Review of Cardiac Blood Flow Function of chordae tendineae and papillary muscles? What opens and closes the valves? Questions: How do the valves work Name the parts & vessels Questions: How do the valves work Name the parts & vessels

30. Micro-structure of Cardiac Muscle Why do the fibers branch? (See Picture - Page 690) Review the key features of the cardiac muscle Autorhythmic fibers - 1% Cardiac muscle fibers - contractile fibers - 99%Review the key features of the cardiac muscle Autorhythmic fibers - 1% Cardiac muscle fibers - contractile fibers - 99%

31. Overview of Cardiac conduction - Autorythmicity l

32. Contractile Fibers Compare and contrast to skeletal muscle Similarities Depolarize - electrically excitable Review of Resting Membrane Potential Why is the outside of the Cell Membrane ++?? What is depolarization?? What ion causes it to happen?? What are the K+ and Na+ found? What is the role of Ca++?

33. Contractile Fibers Compare and contrast to skeletal muscle Role of Calcium Sarcoplasmic Reticulum releases large amounts of Ca++ to effect the muscle contraction.

34. Contractile Fibers Contrasts of Cardiac with skeletal muscle Means of Stimulation Skeletal must be stimulated by nerves Cardiac is innervated (Vagus), but has automaticity or autorythmicity

35. Contractile Fibers Contrasts of Cardiac with skeletal muscle Metabolic rate Larger amount of mitochondria (10-15X) What is the benefit of this?

36. Contractile Fibers Contrasts of Cardiac with skeletal muscle Organ vs motor unit contraction Intercalated discs - for conduction to allow coordinated contraction (skeletal works as motor units).

37. Contractile Fibers Contrasts of Cardiac with skeletal muscle Length of refractory period 250 ms, vs. 1-2 ms in skeletal WHY? Prevents tetanic contractions or �fibrillation� Illustration: raise hands in sequence or �Squirming bag of worms�

38. Contractile Fibers Contrasts of Cardiac with skeletal muscle Depolarization is very different, due to several different types of ion channels for K+, Na+, Ca++ Skeletal muscle more explosive & rapid. Why would cardiac need to be slower? Heart never uses anaerobic metabolismWhy is this important? Strength of contraction can be varied, by the amount of Ca++ allowed in.

39. Sequence of Contraction Page 690-2 RMP? Page 691 picture:

40. Sequence of Contraction (691) 1. Na+ Channels open (Na enters) 2. Slow Ca++ channels open (Ca++ enters) 3. Ca concentration opens Ca++ channels causing contraction

41. �Plateau Phase� (691) 1. Calcium slowly entering 2. Potassium slowly leaving the cell 3. Protracted, sustained contraction

42. Sequence of Repolarization (691) 1. Potassium channels open(also slower, like Ca++) 2.Potassium/Sodium pump restores the RMP

43. Summary Concentration of Ca++ entering determines Ca++ in the SR and the force of contraction (Hence efficacy of Ca++ channel blockers) Entire sequence is about 300 ms (0.3 sec) Limiting factor of maximal heart rate Cardiac muscle is not �all-or-none� like skeletal Slower, consistent contraction

44. Summary What will Calcium Channel blockers do?(2 effects)

45. Summary Very high rate of metabolism Always aerobic Variable force Calcium plays a role in depolarization

46. Control system - Autorythmic Fibers See figure 18.14 on page 694 These fibers have an unstable resting potential due to Na+ & Ca++ leakage in.

47. Control system - Autorythmic Fibers See figure 18.14 on page 694 These fibers have an unstable resting potential due to Na+ & Ca++ leakage in.

48. Control system - role of instability of RMP Sinoatrial node (SA) � Inherent rate of 100 BPM �Sinus Rhythm� � Heart�s pacemaker Location: Upper RA Fastest cells in system

49. Control system - Atrioventricular Node (AV) �

50. Control system - Atrioventricular Node (AV) � Impulse is delayed here 0.1 second (Why?)

51. Control system - Atrioventricular bundle � (Bundle of His)

52. Control system - Atrioventricular bundle � (Bundle of His) The only electrical connection between atria and ventricles Rapidly conducts through Right Bundle branch, (RBB), Left Bundle Branch (LBB) and Purkinje fibers

53. Control system - Right Bundle branch, (RBB), - stimulates septal cells Left Bundle Branch (LBB) � septal cells Purkinje fibers- most important, stimulates most of the ventricular walls, and first stimulates the papillary muscles (why?)

54. Control system - Time required: 220 ms from SA node to complete depolarization. Longer time indicates conduction defect

55. Control system - Clinical Applications Arrhythmias Uncoordinated atrial and ventricular contractions

56. Control system - Clinical Applications Ectopic Foci � Depolarization (beat) originates someplace other than SA node. May be triggered by high caffeine or nicotine Most common cause is low oxygen to a region of the heart Premature Ventricular contractions (PVC�s) most serious.

57. Control system - Clinical Applications Ventricular Tachycardia � rapid rate stimulated by ventricular ectopic foci.

58. Control system - Clinical Applications Ventricular Fibrillation � This is the quivering of muscle � uncoordinated No pumping is occurring Use of defibrillator is indicated here

59. Control system - Clinical Applications Congestive Heart Failure Walls thinning, loss of strength May be on either side (r or l) If on left, fluid builds up in lungs (why?) Treatment: Digitalis � (From poisonous Foxglove family of plants) � slows the rate, but increases strength (contractility)

60. Clinical:What is a �Heart attack�? (Page 692 Btm Left) Ishemia results in: anaerobic metabolism - lactic acid formation: Rising acidity hinders ATP & cannot pump out Ca++, then: Gap junctions close - cells electrically isolated, and: If ischemic area is large, pumping action impaired.