General Principles of Pathophysiology

1
General Principles of Pathophysiology

• Energy Metabolism
• Perfusion
• Shock

2
Topics

• Define shock in terms of cellular function
• Review the requirements for adequate cellular
  perfusion (Fick principle)
• Review the mechanisms for starlings law
• Preload vs. afterload
• Muscle contraction

3
Topics Continued

• Discuss the mechanisms for oxygen transport
• oxyhemoglobin dissociation curve
• Define the stages of shock
• Describe different causes of shock
• Define multiple organ dysfunction syndrome

4
Shock Defined

• Inadequate tissue perfusion
• Anaerobic metabolism

Final Common Pathway!
5
Aerobic Metabolism
6 CO2
6 H2O
METABOLISM
36 ATP
HEAT (417 kcal)
6
Anaerobic Metabolism
2 LACTIC ACID
GLUCOSE
METABOLISM
2 ATP
HEAT (32 kcal)
7
Anaerobic? So What?
Inadequate Cellular Oxygenation
8
Homeostasis is maintenance of balance

• Requires proper functioning systems
• Cardiovascular
• Respiratory
• Renal

9
Physiology of Perfusion

• Dependant on 3 components of circulatory system
• Pump
• Fluid
• Container

10
Factors Affecting The Pump

• Preload
• Contractile force
• Frank-starling mechanism
• Afterload

11
Muscle Anatomy
12
Contraction Sliding Filaments
image from http//www.accessexcellence.com/AB/GG/
muscle_Contract.html
13
What Is Blood Pressure?

• BP Cardiac Output
• X Systemic Vascular Resistance

CO Stroke Volume X Heart Rate
14
What Affects Blood Pressure?

• ANS balance
• Contractility
• Preload
• Starlings law
• Afterload

15
Autonomic Nervous System Review

• Quiz Time! Yeah!

16
Jeopardy

• Controls vegetative functions,exits the CNS at
  high in the neck and low in the back.

What is the parasympathetic nervous system?
17
Jeopardy

• The chief neurotransmitter of the sympathetic
  nervous system.

What is Norepinephrine?
18
Jeopardy

• The cutesy name for the parasympathetic nervous
  system.

What is Feed or Breed?
19
Jeopardy

• Two types of parasympathetic receptors.

What is nicotinic (NMJ) and muscarinic (organs)?
20
Jeopardy

• Two types classes of sympathetic receptors.

What is alpha and beta?
21
Jeopardy

• The cutesy name for the sympathetic nervous
  system.

What is fight or flight?
22
Jeopardy

• Stimulation of this receptor causes an increase
  in peripheral vasoconstriction.

What is alpha 1?
23
Jeopardy

• Stimulation of this receptor causes an increase
  in myocardial contractility.

What is beta 1?
24
Jeopardy

• Stimulation of this receptor causes an increase
  in bronchodilation.

What is beta 2?
25
Jeopardy

• Stimulation of this receptor causes a decrease in
  the sympathetic activation.

What is alpha 2?
26
Jeopardy

• Two types of parasympathetic receptors.

What is nicotinic (NMJ) and muscarinic (organs).
27
Changes in Afterload and Preload
?

• ? Peripheral vasoconstriction

28
Changes in Afterload and Preload
? ?

• ? Peripheral vasodilation

29
Changes in Afterload and Preload
?

• ? fluid volume

30
Changes in Afterload and Preload
?

• ? fluid volume

31
Fluid

• Must have adequate amounts of hemoglobin
• Must have adequate intravascular volume

32
Maintenance of Fluid Volume

• Renin-Angiotensin-Aldosterone system.
• Works through kidneys to regulate balance of Na
  and water.

33
Renin-Angiotensin-Aldosterone

• Plasma
• volume

/Or
? Na
34
Renin-Angiotensin-Aldosterone
Angiotensin II
35
Hemostasis

• The stoppage of bleeding.
• Three methods
• Vascular constriction
• Platelet plug formation
• Coagulation

36
Coagulation

• Formation of blood clots
• Prothrombin activator
• Prothrombin ? thrombin
• Fibrinogen ? fibrin
• Clot retraction

37
Fibrinolysis

• Plasminogen
• Tissue plasminogen activator (tPA)
• Plasmin

38
Disseminated Intravascular Coagulation

• A systemic thrombohemorrhagic disorder with
  evidence of
• Procoagulant activation
• Fibrinolytic activation
• Inhibitor consumption
• End-organ failure

Bick, R.L. Seminars in Thrombosis and Hemostasis
1996
39
Pathophysiology of DIC

• Uncontrolled acceleration of clotting cascade
• Small vessel occlusion
• Organ necrosis
• Depletion of clotting factors
• Activation of fibrinolysis
• Ultimately severe systematic hemorrhage

40
Container

• Vasculature is continuous, closed and pressurized
  system
• Microcirculation responds to local tissue needs
• Blood flow dependent on PVR

41
Fick Principle

• Effective movement and utilization of O2
  dependent on
• Adequate fio2
• Appropriate O2 diffusion into bloodstream
• Adequate number of RBCs
• Proper tissue perfusion
• Efficient hemoglobin loading

42
Fick Principle

• Perfusion Arterial O2 Content - Venous O2
  Content
• Affected by
• Hemoglobin levels
• circulation of RBCs
• distance between alveoli and capillaries
• pH and temperature

43
Onloading Oxygen in Lungs
oxyhemeglobin
pH 7.45

• Remember
• CO2 ? H

pH 7.4
Saturation

• ? pH shifts curve to left
• ? onloading in lungs

deoxyhemeglobin
Pressure
44
Offloading Oxygen in Tissues
oxyhemeglobin
pH 7.4

• Remember
• CO2 ? H

pH 7.35
Saturation

• ?pH shifts curve to right
• ? offloading to tissues

deoxyhemeglobin
Pressure
45
Causes of Inadequate Perfusion

• Inadequate pump
• Inadequate preload
• Poor contractility
• Excessive afterload
• Inadequate heart rate
• Inadequate fluid volume
• Hypovolemia
• Inadequate container
• Excessive dilation
• Inadequate systematic vascular resistance

46
Responses to Shock

• Normal compensation includes
• Progressive vasoconstriction
• Increased blood flow to major organs
• Increased cardiac output
• Increased respiratory rate and volume
• Decreased urine output

47
Cellular Response to Shock

• Tissue
• perfusion

48
Stages of Shock

• Compensated
• Uncompensated
• Irreversible

49
Compensated Shock

• Defense mechanisms are successful in maintaining
  perfusion
• Presentation
• Tachycardia
• Decreased skin perfusion
• Altered mental status

50
Uncompenstated Shock

• Defense mechanisms begin to fail
• Presentation
• Hypotension
• Prolonged Cap refill
• Marked increase in heart rate
• Rapid, thready pulse
• Agitation, restlessness, confusion

51
Irreversible Shock

• Complete failure of compensatory mechanisms
• Death even in presence of resuscitation

52
Types of Shock

• Hypovolemic
• Cardiogenic
• Neurogenic
• Anaphylactic
• Septic

53
Hypovolemic Shock

• Fluid failure
• Decreased intravascular volume
• Causes?
• Third spacing

54
Cardiogenic Shock
? CO
55
Neurogenic Shock
? Sympathetic Tone Or ? Parasympathetic Tone
56
Anaphylactic Shock

• Container failure
• Massive systemic allergic reaction
• Large release of histamine
• Increases membrane permeability vasodilation

57
Septic Shock

• Container failure
• Systemic infection

58
Multiple Organ Dysfunction System

• Progressive dysfunction of two or more organ
  systems
• Caused by uncontrolled inflammatory response to
  injury or illness
• Typically sepsis

59
References

• New York Presbyterian hospital hypertension
  center 
• Http//pc101186.Med.Cornell.edu/htchome/htbk/Htbki
  ndex.htm
• Biographics Gallery http//www.accessexcellence.c
  om/AB/GG/Anchor-Building-11481
• RAS (Renin-Angiotensin-Aldosterone System)
• http//www.science.mcmaster.ca/Biology/4S03/RAS.HT
  M
• A graduate students hypertension page
• http//www.teaching-biomed.man.ac.uk/student_proje
  cts/2000/mnpm6ven/default.htm