Wednesday, March 27, 2013

What is Hypoxia and its Consequences?

This is a general process of oxygen entering into tissue ,and cells.

This process is complex ,troubles in any part will affect the oxygen supply to cell, and lead to hypoxia
Ventilation              Transfer
O2 ——>HbO2  ——> Tissue utilization
      diffusion           Circulatory system

Hypoxia is an extremely important and common cause of cell injury and death.

Hypoxia  is a pathological process, in which O2 supply to tissues or organs is inadequate to meet the demand of cells; or the tissue cells can not make use of O2, leading to changes in functions, metabolisms and structures of cells and tissues of the body.
    The absence of O2 in  the tissues
    A deficiency of O2 in blood

Three key points of Concept :
1. Pathological process
2. Causes 
I)Can’t obtain enough oxygen
II)Can’t fully utilize oxygen
3. Changes  

Oxgen  supply  =  CaO2× Q
Oxygen consumption  =(CaO2-CvO2)× Q

Parameters of blood O2
  1. Partial pressure of  O2 (PO2)
     PO2 is the tension caused by O2  physically dissolved in the  blood.

The normal value :
      PaO2 : 100mmHg (13.3kPa )
      PvO2 : 40mmHg (5.33kPa )

PO2(in the air)  :159mmHg
PO2(in alveolar air):104mmHg

Determinants of  PO2 :
O2 pressure in the inhaled air
respiratory function

abnormal right-to-left shunt in  pathological conditions(e.g. ventricular septal defect)

Ventricular septal defect a common congenital heart defect; an abnormal opening in the septum dividing the ventricles allows blood to pass directly from the left to the right ventricle; large openings may cause congestive heart failure .

2. Oxygen capacity (CO2max)
The maximal amount of O2 combined by hemoglobin (Hb) in 100ml blood.
Fully saturated condition:

The level of  Cp-O2max only depends on Hb :
  ① quantity of HB
  ② quality of HB
 The normal value
Cp-O2max  = 1.34 ml/g × 15 g/dl = 20 ml/dl

3. Oxygen content (C-O2)
The actual amount of O2  in blood.
>combined with Hb : 98.5%
>physically dissolved:1.5%(can be  omitted)
The  level of C-O2 depends on:
  ②The level of Hb (quality and quantity)
 The normal value of  C-O2 :
 CaO2 ——19ml/dl
 CvO2 ——14ml/dl

CaO2 - CvO2 
(Arteriovenous Oxygen content difference) 

normal value:
  19ml/dl -14ml/dl = 5ml/dl  
4. Oxygen saturation(SO2)
 The percentage of hemoglobin present as oxyhemoglobin . 

                                                  O2 content
 SO2 can be calculated by :  —–—–—–—–
                                                 O2 capacity
If 100ml blood contains 20ml O2 , the SO2  is 100%
when it contains 15ml O2 , how much is SO2 ?
 The normal value :
The level of  SO2 only depends on PO2
NOTE: When O2 content in arterial blood is 19ml/100ml, the O2 saturation is 95%, When O2 content in venous blood is 14ml/100ml, the O2 saturation is 70%.

Four parameters
1. Partial pressure of O2(PO2)
              PaO2  : 100mmHg , PvO2: 40 mmHg                                       
2. O2 content(C-O2)
              CaO2  : 19ml/dl , CvO2: 14ml/dl
3. O2 capacity(Cp-O2max)=  1.34 ml/g × 15 g/dl
              C-O2max  : 20ml/dl
4. O2 saturation(SO2) 
               SaO2 : 95%, SvO2: 70%

Classification and pathogenesis
 1. Hypotonic hypoxia 
(1) Decreased O2 pressure in the inspired air.
--- atmospheric hypoxia
①In enclosed room
② 3000 meters above sea level 

(2) External respiratory dysfunctions

Peanuts, jelly or any other soft ,sweet food made from fruit juice and sugar boiled together ,used as a topping.
can cause
Paralysis of respiratory muscles, airway obstruction, asthma, emphysema, tuberculosis, pulmonary cancer, inflammation, and edema.

(3) Right-to-left shunt—Venous admixture
Some congenital heart diseases, such as ventricular septal defect, or if the foramen oval fails to close after birth.

◆ Characteristics of blood O2

-O2 content :↓

-O2 capacity:

acute cases:N
chronic cases:↑

-O2 saturation:↓

NOTE: O2 content ↓(both in arterial and venous blood).    
Oxygen capacity is normal in acute cases and is increased in chronic cases.

   Cyanosis refers to a bluish color of the skin, nail beds and mucous membranes when deoxyhemoglobin concentration of blood in capillary is more than 5g per 100ml blood.
NOTE: Cyanosis is the most important clinical sign of hypotonic hypoxia.
The discolor  of the skin, nail beds and mucous membrane.

Mechanism of Cyanosis
HbO2 (oxygenated Hb) ─bright red
Hb (unoxygenated Hb) ─bluish

Not all the cyanosis means hypoxia

2. Hemic hypoxia (Isotonic hypoxia)
(1) Anemia
The concentration of Hb is less than 9g/100ml。
Patients with severe anemia will have no cyanosis, since their unoxygenated Hb can not reach 5g/100ml

(2) Carbon monoxide  (CO)  poisoning

Mechanism of  CO poisoning
① Hb combine with CO instead of  O2 & produce carboxy-hemoglobin (CO-Hb),the CO-Hb can’t carry O2 any more.
② Hb may combine with both CO and O2 more tightly,so Hb can’t release O2 to tissues.

CO combines with Hb form carboxyhemoglobin (COHb), the color is cherry-red. The cherry-red/pink color will be visible in the skin, nail beds and mucous membrane during CO poisoning. It will have no cyanosis.

(3) Methemoglobinemia
Normal: ferrous state (Fe2+)
oxidized :ferric state (Fe3+)

Hb containing Fe3+ : methemoglobin 

Appearance: Methemoglobin is brown, the patients will appear brown color. 

NOTE: Many chemicals and drugs can oxidize the iron in Hb.(such as: amyl nitrite, aniline, nitrobenzene, acetanilid, phenacetin, and salicylates)
Enterogenous cyanosis

◆ Characteristics of blood O2
     PO2 :N   (isotonic hypoxia)
     O2 content : N or ↓
     O2 capacity : N or ↓
     O2 saturation: N

 3. Circulatory hypoxia
circulatory deficiency
shock, heart failure embolism.

Ischemic hypoxia

Stagnant hypoxia

◆ Characteristics of blood O2
PaO2 :N
C-O2 :N
Cp-O2max :N
SO2 : N

Note: Oxygen supplied for cell in unit time is inadequate.
PO2 in A and O2 content in A are normal; because when blood flow passes through tissues slowly, the PO2 and O2 content in venous blood are decreased. C(a-v) is increased.
C(a-v): ↑ blood flow passes through tissues slowly, the PO2 and O2 content in venous blood are decreased. C(a-v) is increased.

 4. Histogenous hypoxia
Histotoxic hypoxia
(1)  Tissue  poisoning
(2)  cell injured by biological or physical factor
(3)  vitamin deficiency ---vit B1

NOTE:The toxic agent substances include cyanide, arsenic, barbiturates.

◆ Characteristics of blood O2
PaO2 :N
CO2 :N
CO2max :N
SO2 : N

Note: In Histogenous hypoxia;
Cell can’t fully utilize oxygen

The color of skin in hypoxia
1.Anemia —————— pale
2.CO poisoning ———— cherry red
3.Methemoglobinemia—— brown
4.Histotoxic hypoxia—— rose red

Effects on body
Take “Hypotonic hypoxia” for an example
> Functional 
> Metabolic
 mild or chronic hypoxia: compensatory response
 severe or acute hypoxia: organic dysfunction

   1. Respiratory system
PaO2 > 60mmHg:no obvious changes
PaO2 < 60mmHg:compensation

lower segment, Middle, upper segment
remain at  a high level
With the changes in the horizontal axis, vertical axis did not change significantly
The slope is very steep. 

 2. Circulatory system
(1)  In response to hypoxia
I) The heart rate increases (tachycardia),cardiac output increases,due to:
1. Myocardial contractility↑  
2. heart rate↑  
3. venous return↑
II) Peripheral vasodilation occurs.

(2) Pulmonary vasoconstriction
Due to: Sympathetic nerve(+)
        Humoral factors :
       Vasoconstrictive substance ↑↑
       Vasodilative substance↑
significance? --- to maintain the VA/Q

(3) Redistribution of blood flow

 sympathetic nerve(+)---- vasoconstriction
  Local metabolites ----- vasodilation

(4) Capillary proliferation

Capillary hyperplasia

Severe hypoxia ---- decompensation
• Myocardiac systolic and diastolic dysfunction
• Pulmonary hypertension
• Cardiac arrhythmia:
• Venous return↓
Hypoxia  acidosis  hyperkalemia  Arrhythmia

 3.  Hemic system

Hypoxia can stimulate the function of red bone marrow to produce more red blood cells. 

 4.Central nervous system

• Acute  hypoxia  : headache、impaired attention                       
• Chronic  hypoxia : sleepiness, depression
• Severe hypoxia : confusion, coma, convulsion
1. energy deficiency 
2. acidosis 

 5. Cellular alterations
•  Ability to use O2↑:
    number of mitochondia increase
•  Anaerobic glycolysis↑:
    phosphofructokinase activity increase
•  Low metabolic state:
    caused by  acidosis
•  Myoglobin↑

Cellular damage (seen in severe hypoxia) 
(1)Cell membrane 
(3)  Lysosome

Consequences at the cellular level
Lack of ATP may let the sodium pump have no activity, the result is cellular swelling. Hypoxia can increase the cell-membrane permeability, intracellular enzymes enter the ECF.
Myocardial cells contain the enzymes GOT (glutamic-oxaloacetic transaminase), LDH (lactic dehydrogenase), and CPK (creatine phosphokinase), following myocardial infarction the serum levels of these enzymes rise.
GOT and LDH are also abundant in the lungs, liver, pancreas, and kidneys.
Only the heart, brain, and skeletal muscles contain CPK.

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