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General Principles of Pathophysiology

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Excessive HCO3- alkalosis. Simplified: CO2 H Question... Respiratory Alkalosis. Metabolic Acidosis. Metabolic Alkalosis. Respiratory Acidosis. CO2 H20 H2CO3 ... – PowerPoint PPT presentation

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Title: General Principles of Pathophysiology


1
General Principles of Pathophysiology
  • The Cellular Environment
  • Fluids Electrolytes
  • Acid-base Balance Maintenance

2
Topics
  • Describe the distribution of water in the body
  • Discuss common physiologic electrolytes
  • Review mechanisms of transport
  • osmosis, diffusion, etc
  • Discuss hemostasis blood types
  • Discuss concepts of acid-base maintenance

3
Distribution of Water
  • Total Body Weight/ Total Body Water
  • Intracellular - ICF (45/75)
  • Extracellular - ECF (15/25)
  • Intravascular (4.5/7.5)
  • Interstitial (10.5/17.5)

4
Fluid Distribution
Extracellular
Intra- cellular 45 31.5 kg
Interstitial 10.5 7.35 kg
Intra- vascular 4.5 3.15 kg
Cell Membrane
Capillary Membrane
Total Body Weight
5
Fluid Distribution
Extracellular
Intra- cellular 75 31.5 L
Interstitial 17.5 7.35 L
Intra- vascular 7.5 3.15 L
Cell Membrane
Capillary Membrane
Total Body Water
6
Total Body Weight
7
Total Body Water
8
Fluid Intake
Water from metabolism 200 ml (8)
Water from beverages 1600 ml (64)
Water from food 700 ml (28)
9
Fluid Output
Water from lungs 300 ml (11)
Water from feces 150 ml (5)
Water from skin 550 ml (25)
Water from urine 1500 ml (59)
10
Osmosis versus Diffusion
  • Osmosis is the net movement of water from an area
    of LOW solute concentration to an area of HIGHER
    solute concentration across a semi-permeable
    membrane.
  • diffusion of water
  • in terms of water
  • Diffusion is the net movement of solutes from an
    area of HIGH solute concentration to an area of
    LOWER solute concentration.

11
Osmosis
12
Tonicity
  • Isotonic
  • Hypertonic
  • Hypotonic

13
Isotonic Solutions
  • Same solute concentration as RBC
  • If injected into vein no net movement of fluid
  • Example 0.9 sodium chloride solution
  • aka Normal Saline

14
Hypertonic Solutions
  • Higher solute concentration than RBC
  • If injected into vein
  • Fluid moves INTO veins

15
Hypotonic Solutions
  • Lower solute concentration than RBC
  • If injected into vein
  • Fluid moves OUT of veins

16
Affects of Hypotonic Solution on Cell
  • The solute outside the cell is lower than
    inside.
  • Water moves from low solute to high solute.
  • The cell swells and eventually bursts!

Ruptured Cell
Swollen Cell
Swelling Cell
Cell
17
Affects of Hypertonic Solution on Cell
  • The solute outside the cell is higher than
    inside.
  • Water moves from low solute to high solute.
  • The cell shrinks!

Cell
18
  • Infusion of isotonic solution into veins
  • Infusion of hypertonic solution into veins
  • Infusion of hypotonic solution into veins

19
Ion Distribution
Anions
Cations
Na
Cl-
HCo3-
Extracellular
Protein-
PO4 -
K
Ca
Mg
3
Intracellular
20
Example of Role of Electrolytes
  • Nervous System
  • Propagation of Action Potential
  • Cardiovascular System
  • Cardiac conduction contraction

21
Cardiac Conduction / Contraction
22
Composition of Blood
  • 8 of total body weight
  • Plasma 55
  • Water 90
  • Solutes 10
  • Formed elements 45
  • Platelets
  • Erythrocytes

23
Hematrocrit
  • of RBC in blood
  • Normal
  • 37 - 47 (Female)
  • 40 - 54 (Male)

24
Blood Components
  • Plasma liquid portion of blood
  • Contains Proteins
  • Albumin (60) contribute to osmotic pressure
  • Globulin (36) lipid transport and antibodies
  • Fibrinogen (4) blood clotting

25
Blood Components
  • Formed Elements
  • Erythrocytes
  • Leukocytes
  • Thrombocytes

26
Erythrocytes
  • biconcave disc
  • 7-8 mcm diameter
  • Packed with hemoglobin
  • 4.5 - 6 million RBC/mm3 (males)
  • 120 day life span
  • 2 million replaced per second!

27
Leukocytes
  • Most work done in tissues
  • 5,000 - 6,000/mm3
  • Neutrophils (60-70)
  • Basophils (Mast Cells) (lt1)
  • Eosinophils (2-4)
  • Lymphocytes (20-25)
  • Monocytes (Macrophages) (3-8)

28
Thrombocytes
  • Platelets
  • Cell fragments
  • 250,000 - 500,000/mm3
  • Form platelet plugs

29
Hemostasis
  • The stoppage of bleeding.
  • Three methods
  • Vascular constriction
  • Platelet plug formation
  • Coagulation

30
Coagulation
  • Formation of blood clots
  • Prothrombin activator
  • Prothrombin ? Thrombin
  • Fibrinogen ? Fibrin
  • Clot retraction

31
Coagulation
Prothrombin Activator
Clot
Prothrombin
Thrombin
Fibrinogen
Fibrin
32
Fibrinolysis
  • Plasminogen
  • tissue plasminogen activator (tPA)
  • Plasmin

33
Blood Types
  • Agglutinogens (Blood Antigens)
  • Agglutinins (Blood Antibodies)
  • Agglutination (RBC clumping)
  • ABO
  • Rh Antigens

34
Type A Blood
35
Type B Blood
36
Type AB Blood
37
Type O Blood
38
Rh Antigens
39
Capillary Network
  • Blood enters capillary network from arterioles
  • Flows through capillary network into venules
  • Arteriolar capillaries
  • Venous capillaries
  • True capillaries
  • Thoroughfare channels
  • Capillary sphincters

40
Sympathetic Innervation
  • Sympathetic fibers innervate all blood vessels
    except
  • Capillaries
  • Capillary sphincters
  • Most metarterioles
  • Vasoconstrictor and vasodilator fibers

41
Diffusion across Capillary Wall
  • Capillary flow
  • Hydrostatic pressure
  • Osmotic pressure
  • Oncotic pressure
  • Capillary and membrane permeability

42
Edema
  • Fluid accumulation in the interstitial
    compartment
  • Causes
  • Lymphatic leakage
  • Excessive hydrostatic pressure
  • Inadequate osmotic pressure

43
Alterations in Water Movement
  • Edema
  • Fluid accumulation in interstitial spaces
  • Due to any condition that leads to
  • Net movement of fluid out of capillaries into
    interstitial tissues

44
Pathophysiology of Edema
  • Normal interstitial space fluid depends on
  • Capillary hydrostatic pressure
  • Oncotic pressure by blood plasma proteins
  • Capillary permeability
  • Lymphatic channels collect fluid forced from
    capillaries by blood hydrostatic pressure and
    return it to circulation

45
Mechanisms Responsible for Edema
  • Increased hydrostatic pressure
  • Decreased plasma oncotic pressure
  • Increased capillary permeability
  • Lymphatic obstruction
  • Increased capillary hydrostatic pressure
  • Venous obstruction
  • Sodium and water retention

46
Electrolyte Imbalances
  • In addition to water and sodium imbalances, other
    electrolyte imbalances may occur
  • Potassium
  • Calcium
  • Magnesium

47
Potassium
  • Major intracellular cation
  • Needed for nerve, cardiac, skeletal function
  • Excess excreted by kidneys
  • Imbalance can cause sudden death

48
Hypokalemia
  • Poor absorption, vomiting, diarrhea, renal
    disease, diuretics
  • Malaise, weakness, dysrhythmias, decreased
    reflexes, faint heart sounds, hypotension,
    anorexia, vomiting
  • Hospital treatment
  • Oral or IV potassium

49
Hyperkalemia
  • Renal failure, burns, crush injuries, infections,
    excessive use, acidosis
  • Dysrhythmias, irritability, abdominal distention,
    nausea, diarrhea, oliguria, weakness, paralysis
  • Treatment
  • Life threats calcium, glucose, insulin IV,
    albuterol
  • Hospital K restriction, exchange resins,
    dialysis

50
Calcium
  • Essential for
  • Neuromuscular transmission
  • Cell membrane permeability
  • Hormone secretion
  • Bone growth
  • Muscle contraction

51
Hypocalcemia
  • Endocrine dysfunction, renal disease,
    malabsorption
  • Paresthesia, tetany, cramps, neural excitability,
    seizure, abnormal behavior
  • Treatment
  • Calcium administration in hospital

52
Hypercalcemia
  • Tumors, endocrine dysfunction, diuretics, excess
    vitamin D
  • Muscle weakness, renal stones, altered mental
    status, seizures, bone pain, arrhythmias
  • Treatment
  • Underlying problem
  • Diuresis with furosemide and NS

53
Magnesium
  • Activates enzymes
  • 50 in bone
  • Excreted by kidneys
  • CNS effect similar to calcium

54
Hypomagnesemia
  • Alcoholism, diabetes, malabsorption, starvation,
    diarrhea, diuresis, disease with hypocalcemia,
    hypokalemia
  • Tremors, nausea, vomiting, diarrhea, hyperactive
    reflexes, confusion, seizures, dysrhythmias
  • Treatment
  • Magnesium sulfate

55
Hypermagnesemia
  • Patients with chronic renal insufficiency
  • Ingestion of magnesium-containing compounds
  • CNS depression, dysrhythmias, muscle weakness,
    confusion, sedation, respiratory paralysis
  • Most effective treatment hemodialysis
  • Also IV glucose and insulin

56
ACID BASE BALANCE
57
Bottom line of Acid-Base
  • Regulation of H
  • normally about 1/3.5 million that of Na
  • 0.00004 mEq/L (4 x 10-8 Eq/L)
  • Dependent upon
  • Kidneys
  • Chemical Buffers
  • Precise regulation necessary for peak enzyme
    activity

58
pH Effects on Enzyme Activity
59
Acid Base
  • Acids release H
  • example HCl -gt H Cl-
  • Bases absorb H
  • example HCO3- H -gt H2CO3

60
pH is logarithmic
  • pH log 1/H
  • - log H
  • - log 0.00000004 Eq/L
  • pH 7.4
  • Think of pH as power of H

61
pH is Logarithmic
pH is inversely related to H
Small ? pH mean large ? H
62
Buffers Resist pH Changes
  • Weak acid conjugate base pair
  • H2CO3 ? HCO3- H
  • Conjugate Acid ? conjugate base acid

63
Henderson-Hasselbalch Equation
  • pH pKa log base/acid
  • Ex
  • 6.1 log 20/1
  • 6.1 1.3
  • 7.4
  • Key ratio is base acid
  • HCO3- CO2 (standing in for H2CO3)

64
pH Scale
  • 0 Hydrochloric Acid
  • 1 Gastric Acid
  • 2 Lemon Juice
  • 3 Vinegar, Beer
  • 4 Tomatoes
  • 5 Black Coffee
  • 6 Urine
  • 6.5 Saliva
  • 7 Blood
  • 8 Sea Water
  • 9 Baking Soda
  • 10 Great Salt Lake
  • 11 Ammonia
  • 12 Bicarbonate
  • 13 Oven Cleaner
  • 14 NaOH

65
Acid Base Compensation
  • Buffer System
  • Respiratory System
  • Renal System

66
Buffer System
  • Immediate
  • CO2 H20 ? H2CO3 ? H HCO3-
  • Equilibrium 20 HCO3- to 1 CO2 (H2CO3)
  • Excessive CO2 ? acidosis
  • Excessive HCO3- ? alkalosis

Simplified CO2 ? H
67
Question...
  • Is the average pH of the blood lower in
  • a) arteries
  • b) veins

Because veins pick up the byproducts of cellular
metabolism, including… CO2!
Veins! Why?
68
Respiratory System
  • Minutes
  • CO2 ? H
  • Respiration ? CO2 ? H ?
  • Respiration ? CO2 ? H ?

69
Renal System
  • Hours to days
  • Recovery of Bicarbonate
  • Excretion of H
  • Excretion of ammonium

70
Disorders
  • Respiratory Acidosis
  • Respiratory Alkalosis
  • Metabolic Acidosis
  • Metabolic Alkalosis

71
Respiratory Acidosis
  • ? CO2 H20 ? ? H2CO3 ? ? H HCO3
  • Simplified
  • ? CO2 ? ? H

72
Respiratory Alkalosis
  • ? CO2 H20 ? ? H2CO3 ? ? H HCO3
  • Simplified
  • ? CO2 ? ? H

73
Metabolic Acidosis
  • ? H HCO3 ? ? H2CO3 ? H20 ? CO2
  • Simplified
  • Producing too much H

74
Metabolic Alkalosis
  • ? H HCO3 ? ? H2CO3 ? H20 ? CO2
  • Simplified
  • Too much HCO3

75
Normal Values
  • pH 7.35 - 7.45
  • PCO2 35 - 45

76
Abnormal Values
77
All Roads Lead to Rome!
Respiratory Opposes
Metabolic Equals (or doesnt oppose)
78
Example
  • pH 7.25
  • PCO2 60

Respiratory Acidosis!
79
Example
  • pH 7.50
  • PCO2 35

Metabolic Alkalosis!
80
Example
  • pH 7.60
  • PCO2 20

Respiratory Alkalosis!
81
Example
  • pH 7.28
  • PCO2 38

Metabolic Acidosis!
82
Resources
  • A Continuing Education article on Acid-Base
    disturbances is available on our web site at
  • http//www.templejc.edu/ems/resource.htm
  • A great online tutorial at
  • http//www.tmc.tulane.edu/departments/anesthesiolo
    gy/acid/acid.html
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