Hypoxia

Gul Fatima
Lecturer, SICP, Lodhran
Definition

• Hypoxia (oxygen deficiency) is a low level of oxygen in tissue

• Hypoxia interferes with aerobic oxidative respiration and common
cause of cell injury and death.
• Hypoxia may be classified as;
• Generalized  affecting the whole body,
• Localized  affecting a region of the body.

Hypoxemia is characterized by low oxygen content in the blood,

Causes
• Inadequate oxygenation of blood, as in pneumonia
• Reduction in the oxygen-carrying capacity of the blood, as in
- blood loss anemia
- carbon monoxide (CO) poisoning. (CO forms stable complex
with hemoglobin that prevents binding.)
• Lung diseases such as chronic obstructive pulmonary
disease(COPD).
• Cyanide poisoning (Cyanide is a chemical used to make plastics
and other products.)
• Altitude
Signs and symptoms

Although they can vary from person to person, the most common
hypoxia symptoms are:
• Changes in the color of skin, ranging from blue to cherry red.
• Confusion.
• Cough.
• Fast heart rate.
• Rapid breathing.
• Shortness of breath.
• Sweating.
• Wheezing.
 Hypoxia, Ischemia and infarction

• Brain is 1% - 2% of body weight

• It requires a constant delivery of glucose and oxygen from the blood.
• It receives 15% of the resting cardiac output and accounts for 20%
of total body oxygen consumption.
• The brain may be deprived of oxygen by any of several mechanism:
• Functional hypoxia, in a setting of low partial pressure of O2
• Ischemia (transient or permanent): blood flow to a tissue has
decreased, which results in hypoxia.
• Infarction: blood flow has been completely cut off, resulting in
necrosis, or cellular death
 Types of hypoxia
There are following types of hypoxia:
1. Hypoxic Hypoxia
2. Anemic Hypoxia
3. Stagnant Hypoxia
4. Histotoxic/histoplasmic Hypoxia
5. Hypoventilation Hypoxia
1. Hypoxic Hypoxia
• In this the arterial pO2 is reduced.

• O2 content and O2 saturation is

decreased.

• Causes are:
• There is less O2 in inspired air as in high altitudes or closed
room.
• Decreased pulmonary ventilation as in asthma, paralysis of
respiratory muscles, emphysema, airway obstruction, resp. center
depression, etc.
Cont.…..

• Defective gas exchange and O2 transfer due to problems in

respiratory membrane e.g. pulmonary edema
• Defective ventilation-perfusion ratio due to
• uneven alveolar ventilation as in asthma, emphysema,
pulmonary fibrosis, pneumothorax
• due to non uniform pulmonary blood flow as in Anatomical
shunts (Fallot’s Tetralogy)
2. Anemic Hypoxia

• Hypoxia in which arterial pO2 is normal but the amount of

hemoglobin available to carry oxygen is low

Causes:

• Decreased no. of RBC’s

• Decreased Hb content in blood

• Formation of altered Hb

• Combination of Hb with gases other than O2 and CO2

3. Stagnant Hypoxia/ Ischemic Hypoxia
• In which the blood is or may be normal but the flow of blood to
the tissues is reduced or unevenly distributed.

• Insufficient O2 reaches the tissue

• Systemic or local

• Causes
• Congestive Heart Failure
• Hemorrhage
• Surgical stroke
• Thrombosis
• embolism
4. Hypoventilation Hypoxia

• A reduced amount of air enters the alveoli in your lungs, resulting

in hypoxia and hypercapnia

• COPD

• Scoliosis, nasal septum deformation

• Weakened respiratory muscles - motor neuron disease

 5. Histotoxic/histoplasmic Hypoxia:
• In which the tissue cells are poisoned and are therefore unable to
make proper use of oxygen.
• Impaired utilization of O2 by the tissues despite a sufficient
supply of O2 in the mitochondria
• Cyanide poisoning
• Cyanide (HCN) blocks oxidative cellular metabolism by
inhibiting cytochromoxidase
Characteristics
• Low arterial PO2
• Low % saturation of Hb
• Low content of O2
• Low arterio-venous PO2 difference
 Pathological Responses to Hypoxia
• Hypoxia has hazardous effect on organ structure and function,
especially in the case of stroke (cerebral ischemia) and heart infarction
(myocardial ischemia).
• Hypoxia plays also a crucial role in regulating tumor growth and
metastasis.
• The longer the duration of hypoxia/ischemia, the larger and more
diffuse areas of the brain that are affected and the most vulnerable areas
are the brainstem, hippocampus and cerebral cortex.
• Injury progresses and eventually becomes irreversible except if
oxygenation is restored.
• Acute cell death occurs mainly through necrosis but hypoxia also
causes delayed apoptosis
Mechanism
• The first effect of hypoxia is on the cell's aerobic respiration
(oxidative phosphorylation by mitochondria).

• As the oxygen supply decreases, the intracellular generation of

ATP is markedly reduced.

• This reduced ATP has marked effects on many systems within the
cell. It results in increase Na+ influx and K+ outflux of cell.

• Anaerobic respiration (glycolysis) increases because of decrease

ATP and Increase in AMP that stimulate enzyme
Phosphofructokinase.
• This pathway was design to maintain the cell's energy by generating
ATP from glycogen.
• Increase glycolysis also lead to the accumulation of lactic acid thus
lowering the intracellular pH.
• Decrease in pH shift  result further decrease of oxygen supply
occurs.
• Which stimulate the lysosomal enzymes and as result the autophagy
occurs.
• Lastly the cell death occurs.
Diagnosis
• pulse oximetry to determine oxygen levels in the arteries

• gas exchange tests to determine the ratio of oxygen to carbon

dioxide in the arteries

• X-rays or CT scans of the chest and airways

• pulmonary function tests (spirometry, lung volume measurement,

diffusion capacity, and exercise testing)

• tests that measure oxygen levels during the night (nocturnal

oximetry test)
Clinical Features
• Hyperventilation is seen in all types of hypoxia except anemic
hypoxia

• In all types of hypoxia, the first symptoms are like that of alcohol
overdose(drowsiness, depression/excitement, emotional outburst)

• If oxygen saturation of hemoglobin falls below 60% their

unconsciousness within 20 seconds, causing death in 4-5 minutes.

• Severe hypoxia( except anemic) causes increase in heart rate and

systemic blood pressure.

• Associated symptoms- nausea, vomiting and anorexia

Treatment

• Treatment of the underlying cause- depending upon the type of

hypoxia

• Oxygen therapy-

• Inhalation of 100% pure oxygen

• Hyperbaric oxygen therapy

Hypercapnia
• It mean excess of carbon dioxide in the body fluids

• Hypercapnia + Hypoxia  only when the hypoxia is caused by

hypoventilation or circulatory deficiency.

Causes:

• Due to circulatory deficiency  decrease blood flow  decrease

removal of CO2 from tissue  tissue hypercapnia

• High level of CO2 depress respiration  end rapidly in respiratory

death
Symptoms of hypercapnia

• Shortness of breath.

• Headaches.

• Disorientation.

• Paranoia.

• Depression.

• Seizures.

• Confusion or altered mental state.

• Persistent tiredness or sluggishness during the day.

Cyanosis
• Blueness of skin and mucus membrane.

• Definition: Bluish discoloration of skin and/or mucus membrane

due to the presence of at least 5gm of reduced hemoglobin per
100ml of blood in capillaries.

• Cause excess amount of deoxygenated Hb in skin blood vessels

(capillaries)

• Types

1. Central cyanosis

2. Peripheral cyanosis
Central cyanosis
• Pathologic condition caused by reduced arterial oxygen saturation
(SO2).

• It develops when arterial saturation of blood with oxygen is ≤85%.

• Involves highly vascularized tissues, such as the lips, tongue and

mucous membranes, through which blood flow is brisk and the
arteriovenous difference is minimal.

• Cardiac output typically is normal, and patients have warm

extremities.
Peripheral cyanosis
• Normal systemic arterial oxygen saturation and increased oxygen
extraction from peripheral blood, resulting in a wide systemic
arteriovenous oxygen difference

• The increased extraction of oxygen results from sluggish

movement of blood through the capillary circulation.

• Affects the distal extremities, and circumoral or periorbital areas .

Difference
Causes of cyanosis

• Hypoxic hypoxia

• Stagnant hypoxia

• Polycythemia

• Exposure to cold temperatures can indeed lead to cyanosis

vasoconstriction  reduces blood flow to the periphery,  lead to
reduced oxygen delivery to those areas  cyanosis
Treatment

• Oxygen therapy

• correction of metabolic abnormalities (Methemoglobinemia,

Sulfhemoglobinemia, Anemia)

• different types of drugs such as diuretics and ACE inhibitors

Dyspnea
• Shortness of breath (SOB), or air hunger, is the subjective
symptom of breathlessness.
• Causes
• Factors that cause the sensation of dyspnea:
1. Abnormality of respiratory gases in body fluids (mainly
hypercapnia & partly hypoxia)
2. Increase work of breathing by respiratory muscles to breath
forcefully e.g. in asthma
3. State of Mind (neurogenic/emotional dyspnea)-More enhanced
in people who are claustrophobic (fear of not being able to
receive a sufficient quantity of air e.g., small or crowded
places).
4. Heart conditions
Types of Dyspnea
Acute dyspnea
• Acute dyspnea can come on
quickly and doesn’t last very
long (hours to days).
• Allergies, anxiety, exercise and
illness (like the common cold
or the flu) can cause acute
dyspnea.
• More serious conditions, like a
heart attack, sudden airway
narrowing (anaphylaxis) or
blood clot (pulmonary
embolism) can also cause
acute dyspnea.
Chronic dyspnea
• Chronic dyspnea is shortness
of breath that lasts a long time
(several weeks or longer) or
keeps coming back.
• Asthma, heart failure and
COPD can cause chronic
dyspnea.
• Not getting enough exercise
can also make you feel
breathless all the time because
your muscles are trying to get
more oxygen.
Signs and Symptoms

• Some signs of dyspnea include:

• Chest tightness.

• Feeling like you need to force yourself to breathe deeply.

• Working hard to get a deep breath.

• Rapid breathing (tachypnea) or heart rate (palpitations).

• Wheezing (noisy breathing).

 Diagnosis
• Pulse oximetry. The doctor clips a device to your finger or earlobe to
measure how much oxygen is in your blood.

• Blood tests. They can show if you have anemia or an infection and
can check for a blood clot or fluid in your lungs.

• Chest X-ray or a CT scan. They can see if you have pneumonia, a

blood clot in your lung, or other lung diseases. A CT scan puts
together several X-rays taken from different angles to make a
complete picture.

• Electrocardiogram (EKG). It measures the electrical signals from

your heart to see if you're having a heart attack and find out how fast
your heart is beating and if it has a healthy rhythm.
Asphyxia
• It is produced by occlusion of airways

• Simultaneously hypoxia and hypercapnia

• Causes
• Anaphylaxis
• Asthma
• Suffocating
• Strangulation
• Drowning
• Obliteration of blood vessels
 Types
• Mechanical asphyxia: This type of asphyxia occurs when external
forces physically obstruct the airway, preventing the flow of air into the
lungs. Examples include suffocation due to choking, suffocating,
strangulation, or compression of the chest.

• Chemical asphyxia: Chemical substances can interfere with the body's

ability to utilize or transport oxygen, leading to asphyxia. For instance,
carbon monoxide (CO) poisoning prevents oxygen from binding to
hemoglobin, reducing oxygen delivery to the tissues. Hydrogen sulfide
(H2S) and cyanide are other examples of chemicals that can cause
asphyxia by interfering with cellular respiration.
• Drowning: Drowning occurs when the airways is submerged in a liquid,
typically water, and breathing is impaired or prevented. The lack of
oxygen and excessive intake of water can lead to asphyxia.

• Environmental asphyxia: This type of asphyxia is caused by inhaling or

being exposed to gases or environments lacking sufficient oxygen.
Examples include suffocation in a confined space with depleted oxygen
levels, inhalation of toxic gases that displace oxygen, or being trapped in
an environment with a reduced oxygen supply.

• Positional asphyxia: Positional asphyxia can occur when a person's

body position restricts their ability to breathe properly. For instance,
when a person's chest or face is compressed against a surface, or when
they are in a position that compromises the normal mechanics of
breathing, it can lead to asphyxia.
Mechanism

• During asphyxia  hypoxia + hypercapnia  strong stimulation

of respiratory center & violent inspiratory efforts  heart rate
increases, BP increases, Catecholamines increase from adrenal
medulla (increase in nor-epinephrine > epinephrine)  
unconsciousness, convulsions & decrease in respiratory rate 
death.
Stages

• Stage of exaggerated breathing.

• Stage of convulsions.

• Stage of exhaustion and collapse.

Stage of exaggerated breathing

• Lasts for about 1-2 mins

• It is due to powerful stimulation of respiratory center by CO2

• Increased depth of respiration

• Increased ventilation

• Increased respiratory rate

• Dyspnea & cyanosis occurs

Stage of convulsions
• Lasts for about one minute

• It is due to spread of impulse from respiratory centers to other

parts of CNS

• During this period convulsions occurs

• Increased HR-tachycardia

• Increased cardiac output

• Increased sympathetic activity

• Increased vasoconstriction

• Increased BP
Stage of exhaustion and collapse
• Lasts for about 5 min

• Due to lack of O2

• Depression of respiratory center & respiration becomes gasping

• deep respiration with wide mouth

• Pupils widely dilated

• Pulse becomes feeble

• Reflexes are abolished

• Semi consciousness

• Unconsciousness, Coma, Death

Treatment

• Cardiopulmonary resuscitation (CPR) Chest compressions help

keep blood flowing to vital organs until your heartbeat returns.

• Oxygen therapy. A breathing tube, oxygen mask, nose tube or

ventilator delivers oxygen to your body.

• Medications. Medications help treat certain causes of asphyxiation.

They may include an inhaler for asthma, epinephrine (for an
allergic reaction.
Reference

• Kumar V, Cotran RS, Robbins SL. Robbin’s Basic Pathology. 8th Ed. W.
B. Saunders Publishers; 2007.

• Mohan, Harsh. "Textbook of pathology." (6th edition): 842-854.