Transcript General Principles of Pathophysiology

General Principles of
Pathophysiology
Energy Metabolism
Perfusion
Shock
Topics
Define shock in terms of cellular
function
Review the requirements for adequate
cellular perfusion (Fick principle)
Review the mechanisms for starling’s
law
Preload vs. afterload
Muscle contraction
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
Shock Defined
Inadequate tissue perfusion
Anaerobic metabolism
Final Common Pathway!
Aerobic Metabolism
6 CO2
6 O2
METABOLISM
GLUCOSE
6 H2O
36 ATP
HEAT (417 kcal)
Anaerobic Metabolism
2 LACTIC ACID
GLUCOSE
METABOLISM
2 ATP
HEAT (32 kcal)
Anaerobic? So What?
Inadequate
Cellular
Oxygenation
Inadequate
Energy
Production
Metabolic
Failure
Anaerobic
Metabolism
Lactic Acid
Production
Cell Death!
Metabolic
Acidosis
Homeostasis is maintenance of
balance
Requires proper functioning systems
Cardiovascular
Respiratory
Renal
Physiology of Perfusion
Dependant on 3 components of
circulatory system
Pump
Fluid
Container
Factors Affecting The Pump
Preload
Contractile force
Frank-starling mechanism
Afterload
Muscle Anatomy
Contraction: Sliding Filaments
image from: http://www.accessexcellence.com/AB/GG/muscle_Contract.html
What Is Blood Pressure?
BP = Cardiac Output
X Systemic Vascular Resistance
CO = Stroke Volume
X Heart Rate
What Affects Blood Pressure?
ANS balance
Contractility
Preload
Starling’s law
Afterload
Autonomic Nervous System
Review…
Quiz Time! Yeah!
Jeopardy
Controls vegetative functions,exits the
CNS at high in the neck and low in the
back.
What is the
parasympathetic nervous system?
Jeopardy
The chief neurotransmitter of the
sympathetic nervous system.
What is
Norepinephrine?
Jeopardy
The ‘cutesy’ name for the
parasympathetic nervous system.
What is
‘Feed or Breed’?
Jeopardy
Two types of parasympathetic receptors.
What is nicotinic (NMJ)
and muscarinic (organs)?
Jeopardy
Two types classes of sympathetic
receptors.
What is
alpha and beta?
Jeopardy
The ‘cutesy name’ for the sympathetic
nervous system.
What is
‘fight or flight’?
Jeopardy
Stimulation of this receptor causes an
increase in peripheral vasoconstriction.
What is alpha 1?
Jeopardy
Stimulation of this receptor causes an
increase in myocardial contractility.
What is beta 1?
Jeopardy
Stimulation of this receptor causes an
increase in bronchodilation.
What is beta 2?
Jeopardy
Stimulation of this receptor causes a
decrease in the sympathetic activation.
What is alpha 2?
Jeopardy
Two types of parasympathetic receptors.
What is nicotinic (NMJ)
and muscarinic (organs).
Changes in Afterload and Preload
  Peripheral
vasoconstriction…
  peripheral vascular
resistance…
  afterload…
  blood pressure.
Changes in Afterload and Preload
  Peripheral
vasodilation…
 peripheral vascular
resistance…
 afterload…
 blood pressure.
Changes in Afterload and Preload
 fluid volume…
  preload…
  contractility
(Starling’s Law)…
  blood pressure.
  cardiac output.
Changes in Afterload and Preload
 fluid volume…
 preload…
 contractility
(Starling’s Law)…
 blood pressure.
 cardiac output.
Fluid
 Must have adequate
amounts of
hemoglobin
 Must have adequate
intravascular volume
Maintenance of Fluid Volume
Renin-Angiotensin-Aldosterone system.
Works through kidneys to regulate balance
of Na+ and water.
Renin-Angiotensin-Aldosterone
Plasma
volume
Detected by
&/Or
Kidney
(juxtaglomerular
apparatus)
 [Na+]
Via ACE
(Angiotensin
Converting
Enzyme)
Releases
Renin
Converts
Angiotensin II…
Angiotensin I…
Angiotensinogen
Renin-Angiotensin-Aldosterone
 vasoconstriction
 PVR
Angiotensin II…
 thirst
ADH
(anti-diuretic
hormone)
Adrenal
cortex
Fluid
volume
Releases
Aldosterone
 BP!
Na+
reabsorption
Hemostasis
The stoppage of bleeding.
Three methods
Vascular constriction
Platelet plug formation
Coagulation
Coagulation
Formation of blood clots
Prothrombin activator
Prothrombin  thrombin
Fibrinogen  fibrin
Clot retraction
Fibrinolysis
Plasminogen
Tissue plasminogen activator (tPA)
Plasmin
Disseminated Intravascular
Coagulation
“A systemic thrombohemorrhagic disorder
… with evidence of:
1) Procoagulant activation
2) Fibrinolytic activation
3) Inhibitor consumption
4) End-organ failure”
Bick, R.L. Seminars in Thrombosis and Hemostasis 1996
Pathophysiology of DIC
Uncontrolled acceleration of clotting
cascade
Small vessel occlusion
Organ necrosis
Depletion of clotting factors
Activation of fibrinolysis
Ultimately severe systematic
hemorrhage
Container
Vasculature is continuous, closed and
pressurized system
Microcirculation responds to local tissue
needs
Blood flow dependent on PVR
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’
Fick Principle
Perfusion = Arterial O2 Content Venous O2 Content
Affected by:
Hemoglobin levels
circulation of RBCs
distance between alveoli and capillaries
pH and temperature
Onloading Oxygen in Lungs
oxyhemeglobin
pH 7.45
Remember:
CO2  [H+]
pH 7.4
• pH shifts curve to left
• ‘onloading’ in lungs
deoxyhemeglobin
Pressure
Offloading Oxygen in Tissues
pH 7.4
Remember:
CO2  [H+]
oxyhemeglobin
pH 7.35
•pH shifts curve to right
• ‘offloading’ to tissues
deoxyhemeglobin
Pressure
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
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
Cellular Response to Shock
O2
use
Anaerobic
metabolism
ATP
synthesis
Na+ Pump
Function
Tissue
perfusion
Stimulation of
clotting cascade &
inflammatory
response
 Intracellular Na+
& water
Impaired cellular
metabolism
Impaired
glucose
usage
Cellular edema
 Vascular volume
Stages of Shock
Compensated
Uncompensated
Irreversible
Compensated Shock
Defense mechanisms are successful in
maintaining perfusion
Presentation
Tachycardia
Decreased skin perfusion
Altered mental status
Uncompenstated Shock
Defense mechanisms begin to fail
Presentation
Hypotension
Prolonged Cap refill
Marked increase in heart rate
Rapid, thready pulse
Agitation, restlessness, confusion
Irreversible Shock
Complete failure of compensatory
mechanisms
Death even in presence of resuscitation
Types of Shock
Hypovolemic
Cardiogenic
Neurogenic
Anaphylactic
Septic
Hypovolemic Shock
“Fluid failure”
Decreased intravascular volume
Causes?
“Third spacing”
Cardiogenic Shock
R.A.S.
Activation
Volume/
Preload
Impaired
myocardial function
 Catecholamine
Release
 CO
Myocardial
O2 demand
 Dyspnea
 SVR
 O2
supply
Peripheral
& pulmonary
edema
Neurogenic Shock
 Sympathetic Tone
Or
 Parasympathetic Tone
Tissue
perfusion
 Cardiac Output
Vascular Tone
Massive Vasodilation
 SVR & Preload
Anaphylactic Shock
“Container failure”
Massive & systemic allergic reaction
Large release of histamine
Increases membrane permeability &
vasodilation
Septic Shock
“Container failure”
Systemic infection
Multiple Organ Dysfunction
System
Progressive dysfunction of two or more
organ systems
Caused by uncontrolled inflammatory
response to injury or illness
Typically sepsis
References
 New York Presbyterian hospital hypertension center:
 Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.ht
m
 Biographics Gallery:
http://www.accessexcellence.com/AB/GG/#AnchorBuilding-11481
 RAS (Renin-Angiotensin-Aldosterone System):
 http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM
 A graduate student’s hypertension page:
 http://www.teachingbiomed.man.ac.uk/student_projects/2000/mnpm6ven/default.h
tm