FORCED FEEDING

6. METHODS AVAILABLE FOR LONG TERM NUTRITION SUPPORT
1. Nasoenteric tube feeding
2. Gastrostomy tube feeding
3. Jejunostomy tube feeding

6.1 NASOGASTRIC OR NASOENTERIC

Fine bore tubes made of polyurethane or siliconised rubber are
used.
The final position can be checked radiologically.
They are well tolerated with no risk of oesophagecol ulceration or
chest complications.
The patient can learn to insert the tube themself in ambulatory
home entral nutrition.

6.2 GASTROSTOMY

Can be performed by an open surgical procedure when a nasogastric
tube cannot be passed due to an esophageal carcinoma or when
patient is unconscious(fig 5.1)

This procedure can also be done per-coetaneous with the help of
an endoscope (PEG) (Fig 5.2)

6.3 PERCUTANEOUS JEJUNOSTOMY

It is possible to place the tube end in the jejunum through a
percutaneous stab insertion gastrostomy
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URGENT FEEDING

5 Alternative Methods of feeding
ENTERAL FEEDING (Nasogasric or Gastric tube)
Patients with obstruction of upper GIT
Radiation loss of appetite
Full thickness skin burns
Major trauma
These patients will require enteral nutrition.
First because their calorific requirements cannot be met by parenteral feeds
Second those that have nutritonal needs that require long term replacement
The main energy providing constituents of enteral feeds are:

* Glucose or Triglycerides (sunflower seed oils)
Other constituents are:

* Electrolytes
* Minerals
* Trace metals
* And Vitamins

Some enteral feeds can be prepared to meet the specific needs of
Patients by the hospital nutrition departments.

Companies in the enteral food market now provide products that can
Be used to provide all the energy requirements or to supplement
Inadequate oral intake.

Enteral Feeding (Evidence Base)
Animal studies in burn trauma in rats, indicate early external feeding results in improved survival, a delay in feed by 24 hours, result in poor weights, and negative nitrogen balance.
It is suggested that external feeding in trauma restores, the immune / lymphoid tissue function thus maintaining survival, and clearance role, of the gut this protects the portal circulation and liver from bacterial invasion.
There is a body of opinion, that believes that glutamine availablelity, and uptake by the enterocyte for energy in the guts, has a large role to play in insuring the integrity of gut mucosa and its function.
The role of short chain fatty acids produced by colonic bacteria (colonocytes) from fermentation of pectin is another theory that supports enteral feeding 70% of the energy requirements of the coloncytes is derived from these short chain fatty acids a deficiency of these fatty acids threatens the integrity of colonic musosa barrier effect
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SURGERY IN THE STARVED

The nutritional status of surgical patients is crucial, it
affects the post operative recovery,wound healing, convelecsence
and final outcome of the procedure.It is important to assess
the status and correctional action be taken.



4.1 Assessment of nutrition status
The nutritional status may be assessed during general physical
examination and the criteria include :

- Body weight ( compared to ideal for height and age)
- Mid-arm muscle circumference (MUMC)
- Skin fold thickness
- Muscle grip

Nutritional status may also be assessed by investigations:

- Lymphocyte count
- Serum Albumin
- Transferrin levels
- Thyroxine binding pre-albumin

The confirmation of this can be obtained if there has been recent
weight loss of more than 10%.

A body weight less than 80% of ideal for height

- Serum albumin less than 30 gm/l
- Total lymphocyte count below 1.2 x 109/l
- Mid upper arm circumference (MUAC) correlates with BMI cut of 23 cm male & 22 cm females


4.2 Clinical Conditions
The major causes of inadequate intake are the disorders
leading to less than 50% intake of calorie requirements 7-10days
Underlying causes
- Severe dysphagia in the unconscious i.e Head injury, stroke
- Major full thickness burns
- Major Trauma
- Radiation
- Chemotherapy
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NUTRITION IN STARVING SURGICAL PATIENTS

3.3 FATS

Our main problem is supply of calories to a starving surgical
Patient, we need to prevent muscle breakdown loss, and supply
Enough calories for metabololic body requirements

Lipid supplementation can supply high energy source in starving
Patients, without the risk of hyper-glycaemia despite continuing
gluconeogenesis.
In stress and surgery 25-45% of energy can be sourced from lipids.
The fat is limited to 2 gm per Kg/body wt/ 24 hours to avoid fat
overload syndrome (fever, back pain, chills, etc.)

Fat basic facts
In normal circumstances Fats provide the body’s calories requirement (15 – 20%).
In starvation, the majority of calories have to be provided by fat which is converted to ketene bodies produced in the liver.
Steroids, catechols, glucagons, and some cytokines promote lipolysis, while insulin is an inhibitor.
Fat as 20% of non-protein calories in normal or moderate stress conditions seems to be optimal for hepatic protein synthesis.
The fat overload syndrome in parental feeding of fever, back pain, chills, pulmonary Insufficiency, and impairment of the reticuloendothelial system can occur.


4. NUTRITIONAL PROBLEM
All surgical patients cannot be assumed to be in healthy status.
Many patients seeking surgical treatment have been ill, with a
complaint for a variable period ranging from days (acute conditions) to weeks in chronic patients.
During this period their nutritional intake has been affected.
Some may be in alarming state of malnutrition.
Although minor degrees of proteins, and calorie limitation does
not affect the surgical outcome, most severe forms of nutritional
disorders do jeopardize post-surgical recovery, for they effect
wound healing, resistance to infection and thus the recovery
period is prolonged.

The most severe disorder effecting nutrition, are those that
effect oral intake (starvation) and these are disorders of
gastrointestinal tract.

Disorders of an inflammatory nature also cause catabolism and
thus are responsible for the negative nutritional status.
Malignant disorders may also be responsible for disturbing the nutritional status.
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FASTING SURGICAL PATIENT

3.2 CARBOHYDRATES

The human body has an internal supply of stored carbohydrates in the
form of glycogen.
This is enough for a 24 hr. without food intake.
Therefore, glucose (I.V)is the principal means of sparing protiens in a fasting surgical patient.
A minimum of 400 cal in 24 hours can minimise protein breakdown in starvation, it can cut it down by 50%.
In stress state of surgery, and in the presence of sepsis, insulin inhibited lypolysis does not work, thus
gluconeogenesis continues, and hyper-glycaemia occurs.

Wound repair also requires glucose and some amino acid (arginine)
Calories and protiens

Carbohydrates
Glucose is the major energy fuel used by the body.
The maximum rate of oxidation is 4-5 mg/min (7.2 g/ kg/day) 60-70% of body calories requirements are met through carbohydrates.
Carbohydrate stores are virtually depleted after a greater than 24 hours fast, with liver glycogen depleted and only small amounts of muscle glycogen remaining.
In the Krebs tricarboxylic acid cycle, glucose in completle oxidation, produces a larger amount of high energy phosphate, than in the incomplete oxidation of anaerobic glycolysis that produces lactate.
Glucose is an efficient means for protein sparing with at least 400 calories required in 24 hours.
Glucose can reduce the degree of proteolysis up to 50%. Numerous cell types, including muscle, neural tissue, red blood cells can thus be saved.
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PROTIENS IN SURGICAL PATIENTS

Proteins-Summary & Basic information 1
Protein is the most important nutrient because it is required for all body building functions. The utilization of protein as a source of energy is physiologically wasteful.
Amino acids are utilized in three major ways by the body:
1) Protein synthesis
2) Catabolic reactions leading to either urea or carbon dioxide, and
3) Synthesis of nonessential amino acids and other small molecules

Essential amino acids have a carbon skeleton that cannot be synthesized by the body, but requires an external source, i.e. valine, Lucien, isoleucine, lysine, methionine, phenylalanine, threonine, and tryptophan.

Thus, in critical illness, the majority of amino acids are either essential or conditionally indispensable.

Muscle stores of amino acid
Skeletal muscle contains most of the amino acids in the body.
Glutamate comprises 50% to 60% of all white fast-twitch and mixed muscles.
Within 20 hours of an operative procedure or trauma, a large portion of the glutamate store has been depleted.
The importance, of this phenomenon of rapid depletion, followed by slow refilling of glutamate stores is unclear at this time.
Some success has been achieved in preventing glutamate depletion by using glutamate supplementation.
Protein synthesis is modulated by insulin, amino acid supplementation, branched-chain amino acid concentration, and likely human growth hormone, somatomedin, and insulin-like growth factor.
Normally 60% to 100% of daily nitrogen retention is due to the postprandial branched chain amino acid uptake into skeletal muscle.
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LIVER IN METABOLIC RESPONSE

LIVER AND ENERGY SOURCES




2. The Role of LIVER
-The liver is the main handler of all nutrients in our body.
-It extracts 75-100% of all portal vein nutrients in one pass.
-Insulin and glucagons are required for liver function.
-Liver and kidney, both play a role in converting excess nitrogen, ( amino acids) into urea.
-Liver can also use amino acids to form glucose.

3. ENERGY SOURCES
3.1 PROTEINS

In a 70 kg man there is 10-11 kg. of protein.
The daily turnover is 250-300 gm mostly in the form of lost cells from GIT and the enzymes in the secretion of the gut.
Most of these amino acids are re-absorbed, about 1 gm is lost in the stools.
Thus 250 gms are sourced from endogenous protein reserve.
If adequate calorie source is provided (fats, carbohydrates) the required proteins will be re-synthesized using these sources of energy.
Dietary intake of small amount (100 gm) of essential and non-
essential amino-acid containing proteins is required to meet body
requirements.

Proteins are an important nutrient.
It is the resource for the amino acid pool for functional activity of the body through enzymes, contraction of muscles, and immune products. However, it is an uneconomic source of energy, since only one fourth is released on breakdown, compared to three times of this ammount of energy used, in synthesis of new proteins required.
There is also a loss of function with loss of muscle mass.

The end use of absorbed amino acids derived from food
proteins are :

* Synthesis of required proteins
-Plasma proteins 20 gm.
-Hb 8gms,
-WBC and skin 20gms
-Muscle 50 gms
* Catabolism leading to urea (80 gm. urea)
* Production of pyrimidines and purines
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BODY METABOLIC RESPONSE

The Phases of Metabolic Response


1.3 The early phase is also known as Low Flow Phase (Ebb phase) and it occurs immediately after the injury and lasts for 24 hours.
We see a fall in metabolic functions, decrease in body temperature and increase in the levels of stress hormones cortisol,
Epinephrine,
And aldosterone.

1.4 This phase is followed by a Flow phase where the body temperature
and metabolic function rises
There is an increased insulin level, glucose and blood lactate.
With the efficient resuscitative measures the second phase (flow phase) can be brought in earlier.
This is the hyper-metabolic phase and is manifested by an upward
shift in temperature control centre and is a part of the response
to trauma.
Individuals vary in their response to trauma; two important factors are severity of trauma,
And nutritional status of the patient.
Infection also prolongs this phase.
This is the catabolic phase (break down) this phase is because of hypo-volume (loss of blood or fluid) seen in trauma and reduced tissue perfusion, and tends to conserve the bodies resources.


1.5 Anabolic phase.
This is the phase that follows the first two phases and is the phase of rebuilding of the loss resulting from the injury.

This is also called convalescence.
The patient feels better and puts on weight in well treated patients. It starts from 2nd to 10 day onwards.
The hormones required in this phase are insulin and growth
hormone.
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THE EFFECTS OF SURGERY

METABOLISM AND NUTRITIONAL CONSIDERATIONS IN SURGICAL PATIENTS

1. METABOLISM

1.1 Surgical disorders, and surgical interventions, alter the
Internal environment of the patients, and the significant factors are :

* Nutritional deficiency due to the disorder, or the post-operative
starvation
* Metabolic effects of surgical intervention trauma, during, and after the procedure
* Metabolic effects, of physical trauma, in injuries and accidents
* Metabolic effects on cells, and tissues, due to bacterial
invasions in inflammatory disorders
* Tumour burden effects, of uncontroled cell multiplication, and spread
in cancer patients
The main stimulus, responsible for endocrine response, is pain, from the site of
Injury, or disease up along the spino-thalamic tract.
These messages are received in the brain stem, thalamus, and cortex.
The centers in the hypothalamus activate the sympathetic
nervous system and the pituitary. This results in raising serum
levels of :

* Cortisol
* Epinephrine
* Nor-epinephrine
* Aldersterone
* ADH
* Glucagons

1.2 A controlled injury received in surgical interventions is limited.
In cases of trauma, the factors of extent, and severity of injury are
Are variable, the injury occurs outside the hospital, and in many instances severity of injury can only be calculated, from the number of limbs, organs and
body cavities involved.
It has been noted that, the metabolic response, and endocrine response are related to the severity of the injury and in many instances these response may be many times more than the responce caused by a planned surgical interventions.
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SHOCK DISASTER ZONE

12. MULTIPLE ORGAN FAILURE The objective of all treatment of shock is to resuscitate the patient, to restore haemodynamic stability, and to prevent organ failure.
However, due to reasons not clearly understood, and depending on the severity of shock, or persistance of the state of shock, some patients will pass into Multiple Organ failure*.
It begins with pulmonary dysfunction, followed by hepatic, intestinal, and renal failure.
As the number of organs failing increase mortality climbs to 100%.


* also called
MODS (Multiple organ dysfunction syndrome)
MOSF (Multiple organ system failure)
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MORE DRUGS FOR SHOCK

Therapeutic Aids 2





Nor-epinephrine
Norepinephrine is used mainly in patients with hypotension, persisting after volume resuscitation and other Inotrops have been tried.
The sympathetic neurotransmitter nor-epinephrine exerts both alpha and beta adrenergic effects.
The beta adrenergic effects are most prominent at lower infusion rates, leading to increases in heart rate and contractility.
With increasing doses, the alpha mediated effects become evident and are responsible for increases in systemic vascular resistance and blood pressure.

Epinephrine
Epinephrine has a broad spectrum of systemic actions.
At lower rates of infusion Beta-adrenergic responses predominate, leading to an increase in heart rate and contractility (beta 1 effect) in conjunction with peripheral vaso-dilation (beta 2 effect).
These effects result in an increase in stroke volume and cardiac output with a variable effect on blood pressure.
At a higher rate of infusion, alpha effects predominate, leading to an increase in systemic vascular resistance and blood pressure.
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DRUGS FOR SHOCK

Therapeutic aids


Pulmonary Artery Catheter
The differential diagnosis of the shock state is usually relatively straightforward. The clinical setting in conjunction with physical examination is often sufficient to guide diagnosis and therapy.

However, occasionally the cause of the shock state is unclear, in which case homodynamic parameters derived form a pulmonary artery catheter may provide valuable insight into the principal mechanism underlying the shock state.

Inotropes
Volume resuscitation, should precede pharmacological aids.
Drugs should be considered, when tissue perfusion is inadequate, after fluid administration.

Dopamine
Dopamine is an endogenous sympathetic amine, and is a biosynthetic precursor of epinephrine, which also acts as central and peripheral neurotransmitter effect. At low dose (1-3 µg/kg/min) dopamine may increase renal blood flow and diuresis.
At moderate doses (5 µg/kg/min) stimulation of cardiac beta-receptors produces increases in contractility and cardiac output with little effect on heart rate or blood pressure.
With increasing doses (5-10 µg/kg/min), Beta-adrenergic effects predominate, further increases in cardiac output are accompanied by increases in heart rate and blood pressure.
At higher doses (more than 10 µg/kg/min), peripheral vasoconstriction, from increasing alpha-activity becomes more prominent, resulting in
elevation of systemic vascular resistance,
blood pressure,
and myocadial oxygen consumption.

Dobutamine
Dobutamine is a synthetic adrenegic agonist.
The predominant effect is an increase in cardiac contractility with little increase in heart rate.
Dobutamine also has a peripheral vasodilating effect resulting from Beta2-receptor activation that is independent of any increase in cardiac output.
The combination of increased contractility, and reduction in afterload, contribute to improved left ventricular emptying and a reduction in pulmonary capillary wedge pressure.
As a result of these properties, dobutamine is an ideal agent when the therapeutic goal is to improve cardiac output rather than to improve blood pressure.
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SHOCK TREATMENT CHOICES 2

Hypertonic Saline


The logic behind the use of hyperosmotic soultions in patients with hypovolemic shock is
-The hypertonic component of these solutions draws water out of the intracellular space and expands the volume of the extracellular space.
-To increase the intravascular osmotic pressure 6% dextran has been added to the hypertonic saline solution.
-The colloid component holds the newly arrived readmitted fluid in the intravascular space and thus, should prolong the beneficial effects of the hypertonic solutions. Based on published data, hypertonic saline with or without dextran offers a little benefit than standard resuscitation regimes.
• In-patients with shock and traumatic brain injury the brain edema hypertonic saline may offer some benefit in the form reducing edema.
• Hypertonic saline as method of small volume resuscitation may also offer some advantages in prolonged transport or longer evacuation periods times require of resuscitation with limited supplies.
• Additionally, the small weights and volumes of hypertonic saline required for resuscitation may prove of advantage in stored supplies for the war and disasters.
Use of Colloids


It is uncertain whether the use of colloid solutions has any benefit over the use of crystalloid solutions.
Analysis of randomized, controlled trials, comparing albulmin to crystalloid, have suggested that use of colloid solutions, in resuscitation may in fact increase mortality.
It is thought that albumin, for instance may increase edema , impair sodium and water exeretion, and worsen renal failure.
There are two forms of synthetic colloid in use.
-Hetastarch, a 6% hydroxyethyul starch solution, has a significant volume expanding effect that lasts as long as 24 hours.
-Potential disadvantages with the use of hetastarch, include rare anaphylaetic reactions, and the development of a coagulopathy, when given in excess of 100ml/day.
Clinical trials, with this agent have shown improvements in tissue perfusion, without any difference, in clinical outcomes.
-Pentastarch is a synthetic colloid, with several advantages over hetastarch.
Its structure allows for a more concentrated solution, and therefore higher osmotic pressures, for plasma expansion, and faster plasma clearance, and renal excretion
This new solution, has been proved to cause less allergy, and is associated with fewer renal, or anaphylactic complications.
Pentastarch has a volume expanding effect that lasts approximately 12 hours in comparison to herastarch (24 hours). Approximately 90% of the pentastarch given is eliminated form the intravascular space within 24 hours.
Pentastarch induces plasma volume expansion of about 1.5 times the volume introduced, whereas hetastarch produces expansion approximately equal to the volume administered.
Thus pentastarch may be a more potent volume expander with a shorter duration of action than either hetastarch or albumin
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SHOCK TREATMENT OPTIONS & CHOICES

11. TREATMENT OF SHOCK(Causative & General)
- Take into consideration the etiological classification discussed above, you will have diagnosed the underlying causative factor, and correction undertaken rapidly.
-The general treatment measures include.

11.1. Oxygen Inhalation Check Airway : This has special reference
to wounds of the chest. If oxygenation is deficient and
patients are cyanosed, it may need to be combined with
Intermittent positive pressure ventilation with 100% O2
After intubations.

11.2. Infusion + Transfusion
Two large bore infusion
lines are started in
Severe shock 1-2 liter
of Ringer's lactate are
infused, if blood is
Lost fully cross
Matched whole blood is
Of great importance in
cases. In the group of
cases which do not
respond to intravenous
blood transfusion O group packed cells can be given. The
recommended fluid requirements are given in table.

Disadvantages of Blood
-Grouping and cross matching takes time
-Stored blood has high potassium,fragments of platelets,and WBC
-Blood maybe infected with malaria,HIV,HBV
-Viscosity of blood in microcirculation may require fluids other than blood

Selection of Fluid
The most cost effective approach is with rapid infusion of isotonic (Normal) saline or a balanced salt solution.
-Infusion of 2 to 3L of crystalloid over 10 to 30 min should restore adequate intravascular volume in most cases as the result of fluid input and distribution.
-In patients with hemorrhagic shock, restoration of blood volume with crystalloid usually requires at least three times the estimated blood loss.
• If blood pressure does not improve after rapid administration of 21 of crystalloid, this suggests that blood loss is in excess of 1500ml, or there is ongoing active bleeding, or, alternatively, another cause of shock must be considered.
• Volume resuscitation in hemorrhage should include simultaneous blood transfusion, either as fully cross matched blood, type specific blood, or, in some circumstances, O-positive or O-negative packed cells.
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SHOCK TREATMENT CONCERNS

10. HEMORRHAGE
Treatment concerns
What concerns us most, in this section are the effects, of the
loss of whole blood, from torn blood vessels in the injured part.
This hemorrhage may be external, if the skin has been torn (visible loss), or it is internal into body cavities or tissue spaces, and cannot be estimated.

10.1 The clinical state of shock, that follows, also depends
on, the rate at which blood is lost and this is dependent upon :

-The extent of injured area(number of torn vessels)
-Vessels injured, whether these are arteries where the loss is
much greater, or veins when the loss is much less, over time.
Injury may also be to the capillaries, with the least amount
of blood loss.

-The size of the blood vessels-major arterial injury can
produce extreme blood loss, over a short time eg.
injuries to the aorta.

10.2 The hemorrhage may occur immediately on receiving
injuries, or later when the initial clot formed at that time is dislodged.

Intravenous fluid delivery
Resuscitation of hemorrhagic shock or severe hypovolemia, requires two large bore (16 gauge or larger) intravenous lines, for rapid volume expansion.
Access may be achieved by peripheral vein catheterization.
Cut downs on the basilic, greater saphenous, or cephalic veins
Or percutaneous central venous access via subclavian, internal jugular, or femoral venous puncture.
The most important consideration for vascular access, is the choice of catheter and tubing. The rate of flow is proportional to, the fourth power of the radius of the canulla, and is inversely related to its length.
Thus a short large bore catheter connected to the widest administration tubing or direct insertion of beveled tubing via a cut down venotomy provides the most efficient restoring of circulating volume.


Treatment of hypo-volemic shock aims at two primary goals at the same time, they are;
-To re-expand the circulating blood volume and
- A surgical interventions, to control any further blood volume loss.

Adequate replacement of the circulating volume,
-Expands vessels & restores venous return, -
-This reestablishes ventricular filling.
These results in, improved left ventricular end diastolic volume,-> contractile function, and stroke volume improved
The cardiac output responds positively,- as cardiac output improves, this leads to systemic vascular resistance returning to normal- and tissue perfusion improves
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SHOCK MONITORING MODERN TECHNIQUES 2

9.1.3 Transcutaneous O2 monitoring

This noninvasive technique for measuring skin PO2 is dependent on
cardiac output and skin perfusion in a stable patient but not in
patients in shock

Gastric Tonometry
Gut perfusion, can be indirectly assessed, using tonometric techniques, to measure the gastric intramucosal pH (pHi).
- Involves instilling saline into a semi permeable balloon, at the end of a modified nasogastric tube, after a period of equilibration, remove the saline and measure the carbon dioxide tension (Pco2), of the saline sample.
-Mucosal ischemia, leads to the production of increased CO2 within the stomach lumen, which is detected as an increased Pco2, in the saline sample.
-Gastric mucosal Pco2 is used with measured arterial bicarbonate to calculate the pHi. -Trauma patients with pHi less than 7.32 have a higher rate of MOF and death.
-Recent technical innovations, have lead to the development, of a semicontinuous gas tonometer, and a model of this device is now available for clinical use.
Gut perfusion using this technique is detected by an elevated mucosal-arterial CO2 gap.
Gas tonometry is automated, and less prone to sampling error.

9.1.4 Serum Lactate

The more important information comes from demonstrating rising or
falling serum lactate levels in response to treatment of shock.
The lactate/pyruvate ratio is also of help in this regard.

Recent developments have led to the availability of bedside testing of serum lactate levels, and an effective clinical method of determining perfusion status through serial measurement of lactate at the bedside in critically ill patients.

In summary it is observed that in shock resulting from
decreased blood volume (oligaemia) there would be on INVESTIGATION:
i)A decreased cardiac output
ii)An increased peripheral resistance and
iii)Decreased central venous pressure


Metabolic effects of untreated shock include:
* A decreased, oxygen consumption
* Hyperglycaemia followed by hypoglycaemia in late stages
where glycogen stores have been depleted
* A rise in blood lactate and pyruvate
* Metabolic acidosis
* Increase in ACTH secretion
* Decreased urine output (<0.5 ml.kg body wt.)
Modern techniques can help give you information, if you look for it
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SHOCK MONITORING MODERN METHODS

9.1 MODERN TECHNIQUES

Pulmonary artery catheterization usng Swan-Ganz catheters can
supplement the parameters discussed above.
It is required in
-Major trauma,
-High risk surgical patients,
-Cardiac surgery or
-Diagnosis is uncertain.
It is passed per-cutaneous through internal Jugular or Subclavian veins into the right atrium, right ventricle, and into the pulmonary artery.
Proper placement shows the dichrotic pulmonary/artery wave.
The balloon is inflated and the wave form shows the pulmonary capillary wedge pressure (PCWP) this represents, left ventricular preload pressure.
Cardiac output can be measured using thermo-dilution techniques.
Some of the parameter used in monitoring a shock patient are given in table 4.2.

The volumetric oximetery PAC measures right ventricular volumes, has proven to be very useful in the care of critically ill patients.
This modified PAC measures beat to beat temperature changes with sampling, from which the right ventricular ejection fraction (RVEF) is calculated.
This technology improves the clinician’s ability to estimate preload, contractility, and afterload.
Continuous mixed venous oxygen saturation (Svo2) monitoring using fiber optics incorporated into the PAC has been available and monitoring Svo2.
The ability to continuously monitor cardiac output represents a recent advance in PAC technology. Monitoring systems that measure cardiac output as often as every 15 seconds are now available.

9.1.1 Continuous Cardiac Output

The most widely used method is noninvasive skin electrodes that
measure small amplitude alternating current.

Invasive and non-invasive Doppler methods have been used to
provide continuous cardiac output measurement.

9.1.2 Mixed Venous Oxygen

This is possible with a modified pulmonary artery catheter with a
Fiber-optic bundle, and use of reflectance spectrometer.
This technique can give us mixed venous oxygen saturation
SV(overbar)O2.

The arterial base deficit (BD) represents a rapid, widely available measure of post-traumatic metabolic acidosis.
-This variable is calculated from directly measured values of arterial pH and arterial carbon dioxide tension (Paco2) from an arterial blood gas sample
-Persistently elevated values of BD throughout the resuscitation period have been correlated with impaired oxygen utilization, and may provide insight into the adequacy of ongoing resuscitation and therapy.
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SHOCK SPOT AND TREAT

8. PRESENTATION OF SHOCK

A patient with a history of having had any one of the causative
events listed under Shock syndrome presents with:

* Pallor best seen on the face
* Cold moist skin of the extremities(vasoconstriction of skin
vessels)
* Rapid weak pulse (>90/min) and a collapse of superficial veins
because of compensatory peripheral vasconstriction
* Cyanosis and rapid shallow breathing (air hunger)
* Patient may have tendency to vomit and is restless,
later there may be diminishing sensibility, drowsiness and
coma
** On examination there is a declining pulse pressure
followed latter by a drop in blood pressure (systolic < 90 mm
of Hg)

9. MONITORING

In an average hospital or Nursing home, the patient with any of the shock syndromes, is observed, and progress assessed, recording the following
parameters:

* Blood pressure
* Central Venous pressure
* Haematocrit
* Arterial blood gases
* Urine output

All these values, if altered, are the late manifestations of shock.
Thus it is difficult to assess the treatment of shock.
Normal values may not reflect reversal of shock and give no indication of tissue perfusion or O2 debt. Thus silent hypoxia remains undetected.
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SHOCK INTERNAL EVENTS

7. PATH PHYSIOLOGY OF SHOCK

Hypo-perfusion, and O2 lack, are common to all types of shock
syndromes.
Shock syndromes, may vary in severity, from silent tissue hypoxia,
to multiple organ failure.
In cases of septic shock, hyper-dynamic circulatory state, is
accompanied by a high O2 debt, due to excessive O2 demand in the presence of infection resulting in hypoxia.

Any Impaired tissue perfusion, leads to low delivery of oxygen in
relation to tissue needs,this is the basic cause of shock state.
The precise role of hypoxia, in pathogenesis of shock, is not clear as yet.
With improved techniques, it is hoped this role will be better
understood. However the events that follow shock states are;

7.1 Acidosis

As the oxygen delivery is deficient to meet O2 demand of tissues,
anaerobic glycolysis (breakdown) starts.
In the absence of O2 pyruvate is converted to lactate, and two molecules of adenosine troposphere (ATP) are made available.
In cases of adequate O2 3 molecules of ATP are released per one molecule of glucose utilized.

As the O2 diminishes, lactate increases and pyruvate diminishes.
This high Lactate level has been correlated with survival in
studies where lactate concentration increase beyond O-2m mol per
liter.

The effects of metabolic acidosis are;
-bradycardia,
-vasodilatation,
-decreased cardiac output and
-ventricular fibrillation.

7.2 Circulatory Redistribution

As a result of hypoxia, the homeostatic response is to preserve
oxygen delivery, to heart and the brain.
This is achieved by diverting blood flow, from other organs (skin, GI tract).
This is achieved through vasoconstriction of skin and visceral
circulation.
The agents responsible for this vasoconstriction
are :

* Catecholamine
* Angiotensin-II
* Vasopressin
* Endothelin
* Thromboxane A2

The changes in microcirculation in redistribution of blood flow
leads to slowing of flow, high viscosity of blood and sludging,
leading to intravascular coagulation and occlusion of capillary
channels.

As a consequence, intestinal mucosal injury occurs, gut
permeabilty may increase, and enteric bacteria and toxins move
across the gut wall, and invade the circulation via lymphatics and
portal venous system.
This is known as bacterial translocation.
Thus, the end effect of vasoconstriction in gut circulation can
lead to ischaemia and irreveresable shock, SIRS and MODS.
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SHOCK COMPENSATORY CASCADE

6. COMPENSATORY MECHANISM
6.1 The baroreceptors in the aortic arch and carotid sinus receive the signal of falling BP and send less afferent stimuli to the vasomotor centre in the medulla.
This results in enhanced sympathetic tone ending in arteriorlar and venous constriction.
There is increase in the after load and increase in venous
return to the heart (increase pre-load).
The vascular constriction is least in cardiac and cerebral circulation.
The enhanced adrenal medullary output of catacholamines results in
increased heart rate and mycardial contractility.
All these mechanisms improve cardiac output.

6.2 Antidiuretic hormone (ADH) is also released from the
posterior pituitary in response to the hypovolemia.
This ADH produces vaso-constriction in the visceral circulation and
increased re-absorbtion of water from the distal tubules of the
kidney.

6.3 Renin secretion is also stimulated by the hypo-perfusion of
juxta-glomerular apparatus in the kidney.
This leads to formation of angiotensin-I in the liver and later to angiotensin-II in the lungs.
This angiotensin-II is a powerful vasoconstrictor. This
is also a signal for release of aldersterone from the adrenal
cortex.

6.4 The aldersterone is a valuable restorer of circulating volume
by re-absorbtion of sodium from the renal tubules.
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SHOCK TO RECOGNISE AND MANAGE

5. MANAGEMENT
HYPOVOLEMIC SHOCK is the common form in practice, we use this form as working model.

The signs and symptoms appear only when the loss from
the circulatory system is above a certain volume usually (750 cc)
The compensatory mechanism fail and tissue perfusion suffers as
a result.
A summary of these volume losses and manifestations
in a seventy kilogram man are given below:


-Thus the first sign may be a rise in pulse rate because of increase in catecholamine.
-As the loss of blood or fluid continues the pulse rises and the systolic BP falls.
-The urine production per hour drops.
-The mental state passes through stages of apprehension, anxiety and lethargy to coma

A clinical staging system of hemorrhagic shock based on the percentage of acute blood volume loss has been described

Typically
-Classes I(Loss of 750cc of blood) and II(loss of 750-1500) are referred to as compensated shock states in which the adrenergic response maintains a normal blood pressure.
-Passing from a compensated state of shock to class IV (uncompensated) shock may occur rapidly in children and young adults.
-De-compensation of homeostatic mechanisms and inability to maintain systolic blood pressure above 90 mmHg after trauma induced hypovolemia are associated with a mortality of more than 50%.
However, rapid and adequate restoration of circulating blood volume simultaneous with control of bleeding can reverse even severe hemorrhagic shock.
It is thus crucial to recognize compensated shock early and intervene with speed for good results.
Laboratory evaluation may provide some diagnostic information.
- Non hemorrhagic forms of hypovolemic shock cause hemoconcentration.
- If there is loss of free water, then hemoconcentration will occur with hyponatremia.
- Following acute hemorrhage there may be no alteration in the hemoglobin or hematocrit values when compensatory fluid shifts occur fluids are administered hemoglobin and hematocrit will drop.
In clinical situations in which the cause of underlying shock state is not clear, the most critical decision is to ensure that cardiogenic shock is not cause.
The findings of jugular venous distension, rates, and the presence of an S3 gallop in cardiogenic shock may assist in diagnosis.
Both forms of shock, however, are associated with a reduction in cardiac output and a compensatory sympathetic mediated response.
Further, both types of shock may be treated with, and respond to, volume resuscitation.
If the diagnosis is in doubt or the clinical situation suggests both as a possibility, then invasive monitoring with a pulmonary artery catheter may required to assess effect of therapy.
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SHADES OF SHOCK 5

4.5 Decreased respiratory ventilation and SHOCK LUNG
There is a decrease in available O2 in these in all cases as OF:
i) Pneumothorax
ii) Pulmonary embolus
iii) Shock lung or adult respiratory distress syndrome (ARDS).
This is met with in trauma, sepsis, aspiration of
gastric contents, and pneumonia

All these conditions lead to injury to the lung
tissue resulting in damage to the alveolar epithelium/
Capillary bed interface producing leakage of protein
Rich fluid into the interstitial space and later into
The alveolar space leading to respiratory distress.
This impairs gas exchange capacity of the lung The clinical features of ARDS of hypoxia, low lung
compliance and all these conditions interfere with
tissue perfusion with O2 because of impaired gas
exchange.
A diffuse interstitial pattern on X-ray is
visible.

4.1.1+ 2 and 4.3 are due to Pre-load and after-load effects
while 4.4 is due to cardiac muscle fuction impairment (infarct
/compression). All have low available O2 in the
blood.
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SHADES OF SHOCK 4

4.4 Cardiogenic shock occurs most often as result of i) Myocardial infarction (MI) ii) Tamponade (collection of blood in the pericardium due to leak from the myocardium) This shock is due to cardiac muscle being unable to maintain
adequate cardiac output from causes intrinsic to the heart
muscle such as MI, cardiomyopathy, or drug toxicity or causes
extrinsic to heart muscle such as compression i.e. tamponade,tension pneumo- thorax or pulmonary embolus (3.3).

Cardiogenic Shock
The syndrome of cardiogenic shock is defined as the inability of the heart (as a result of reduction of its pumping function) to deliver sufficient blood flow to the tissues to meet resting metabolic needs. Thus, the clinical definition of cardiogenic shock requires a low cardiac out put and evidence of tissue hypoxia in the presence of an adequate intravascular volume. -If hemodynamic monitoring is available, the diagnosis is confirmed by the combination of a low systolic blood pressure and a depressed cardiac index (<2,2 l/min/m2) in the presence of an elevated pulmonary capillary wedge pressure (>15mmHg)
-A reduced blood pressure activates the baroreceptors.
-The adrenergic response leads to an increase in heart rate, myocardial contractility, and arterial and venous vasoconstriction.
-The renin angiotensin system is activated by inadequate renal perfusion and sympathetic stimulation, leading to additional vasoconstriction and salt and water retention.
Finally, hypotension increases the secretion of antidiuretic hormone, which further increase water retention. The reduction in blood pressure in conjunction with an elevated left ventricular end diastolic pressure resulting from fluid retention and low left ventricular function reduces coronary perfusion pressure and thus myocardial oxygen delivery.
Increase in heart rate, systemic vascular resistance, and contractility all increase myocardial oxygen consumption and demand.
-The difference between myocardial oxygen demand and oxygen delivery further reduces left ventricular function and will lead to circulatory collapse.
The clinical picture of cardiogenic shock is remarkably similar to those of hypovolemic shock.
-In making the diagnosis of cardiogenic shock, history of cardiac disease may be of great value. -Physical exam demonstrates inadequate tissue perfusion with an elevated jugular venous pressure, an S3 gallop, and pulmonary edema. -A chest radiograph provides diagnostic information regarding the presence of pulmonary edema, pleural effusion, or cardiac chamber enlargement.
-Cardiac enzymes may provide evidence of acute myocardial infarction.

Arterial blood gas analysis provides information regarding the adequacy of gas exchange. Severe hypoxia in the presence of a normal chest radiograph may support the diagnosis of massive pulmonary embolus rather than a primary cardiac cause of shock.
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SHADES OF SHOCK 3

4.3 Neurogenic shock due to decreased peripheral resistance
resulting from:
I) Increase vagal tone as in case of severe pain,
intense emotion, can lead to slow heart rate.
ii) Spinal anesthesia leading to loss of sympathetic impulse
And enlarged blood vessels-leads to pooling of blood


Neurogenic shock, can occur in severe injury to the spinal cord/
head injury-results in failure of the sympathetic nervous
system resulting in insufficient vascular tone.
The vasodilatation and increased venous capacity results in less
cardiac filling (3.1) and poor vascular resistance-less tissue perfusion and shock .

Neurogenic Shock
Hypotension and bradycardia may occur following acute cervical or high thoracic spinal cord injury.
-This result from blockage of sympathetic outflow in presence of unopposed vagal tone result in clinical features referred to as neurogenic shock,
-The diagnosis should be suspected in any patient with hypotension and bradycardia following injury.
-In some cases, these findings may represent the first suggestion of a spinal cord injury in a comatose patient.
-The patient with neurogenic shock is typically warm and well perfused.
-If a pulmonary artery catheter is in situ, the cardiac index may be elevated while the systemic vascular resistance is markedly reduced.
-Occult hemorrhage should be ruled out before attributing spinal cord injury as the exclusive cause of hypotension.
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SHADES OF SHOCK 2

4.2 Bacteraemia (septic shock)
Also named, Toxic shock, and Distributive shock.
It is diagnosed more often in surgical practice today.
There are more aged, immune-compromised patients in hospital.
There are more implants and interventions.
There are more post trauma admissions.

*Septic Shock
Septic shock is the second most frequent cause of shock in the surgical patients.
Invasive bacterial infection represents the most common cause of septic shock, with the most likely sites of infection being the lungs, abdomen, and urinary tract.
Bacterial products cause release of cytokines, tumor necrosis factor-alpha (TNF –alpha) and thromboxanes platelet activating factor, prostaglandin’s etc.
The inflammatory milieu induces several circulatory changes
First, myocardial depression is often evident despite an increase in cardiac index. Several factors contribute to cardiac dysfunction, including biventricular dilatation, myocardial hypo-responsiveness to catecholamine, and diastolic dysfunction.
-Together these phenomena result in a significant reduction in ejection fraction and a sub-optimal response to volume infusion that persists for as long as 10 days.
-The increase in cardiac index despite a reduction in myocardial contractility occurs as a result of a profound reduction in vasomotor tone, the principal cause of hypotension in septic shock.
-The reduction in venous tone leads to pooling of blood in large capacitance vessels, effectively reducing circulating blood volume.
-Several microcirculatory changes also occur distinct from change in vasomotor tone.
These also play a role in the manifestations of septic shock.
The mediator environment of sepsis,
-results in activation of the coagulation cascade,
-leading to micro-thrombus formation, leading to capillary plugging.
This micro-vascular occlusive phenomenon induces the opening of arteriovenous shunts, effectively depriving tissues of adequate perfusion.
Several pro-inflammatory mediators also increase neutrophil endothelial adherence and subsequent exit of activated inflammatory cells into the interstitium where they induce tissue injury.
Increased vascular permeability results in edema which effectively increase the distance required to be covered for cellular oxygen delivery and the opening of arterio-venous shunts, induces cellular hypoxia.


Clinical
Early manifestations of severe sepsis, include, tachypnea, tachycardia, oliguria, and changes in mental status.
-Thus, these simple clinical features should be considered evidence of impending shock in those at risk.
-These clinical features may be followed by the onset of fever and leukocytosis.
Early aggressive management is required to minimizing the morbidity and mortality of septic shock.
- The systemic vaso-dilation and increase in micro-vascular permeability result in patients to require large amount of intravenous fluid to restore a normal blood pressure.
- Vasopressors used are dopamine, epinephrine, or nor-epinephrine if there is an inadequate blood pressure response to fluid resuscitation.
- In-patients not responding to fluid infusion or those with underlying cardiac of renal disease, the use of pulmonary artery catheter is indicated.
- The resuscitation process is incomplete without all measures to reverse the infections process as early as possible.
- The correct choice of antibiotic or antibiotic combination is required.
- If the infection source is an abscess or there is a prior soiling of the pleural or peritoneal cavities, then either drainage or control of contamination is mandatory.
- Similarly, necrotic, infected tissue requires aggressive debridement.*
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SHADES OF SHOCK

4. Shock Syndromes

The events of shock may result from:

4.1 Oligemic (Hypo-volemic) shock due to decrease in circulating
blood volume resulting from :
i) Hemorrhage (internal or external)
ii) Loss of fluid as in burns,trauma(Third space) or
dehydration
iii) Decreased extra-cellular fluid because of hypo-natreamia
as in Addison's disease

Hypovolemic shock occurs most often following trauma resulting
in blood loss.
It also occurs following GI bleeds, or a leak from an aneurysm.
Plasma volume losses can occur in trauma, burns, intestinal obstruction, diarrhea and heat stoke.
*Hypovolemic shock
Hypovolemic shock is the most common cause of shock. It may occur as a result of one of two events:
1. hemorrhage, representing intravascular volume decrease through the loss of whole blood or
2. loss of plasma volume through extra-vascular fluid loss or fluid loss from gastrointestinal, urinary tracts, and insensible loss.
-Hemorrhage is the form of volume loss that is common in practice can be measured and studied and thus is the better understood form of shock.
-Extra-vascular internal fluid leak, also referred to as “third space” fluid losses, is frequently unnoticed as a cause of shock.
-Third space fluid losses are the principal cause of volume loss in the early postoperative period and in local inflammatory processes, such as pancreatitis, in which local changes in capillary permeability result in fluid extravasations from the intravascular space into the interstitial space.
-Fluid leak is the principal cause of shock in patients with small bowel obstruction.
In this case, volume loss results from fluid loss into the interstitial space, bowel lumen, and exudation of fluid into the peritoneal cavity.
-The clinical manifestations of nonhemorrhagic forms of hypovolemic shock are the same as with hemorrhage, although they can be more slow in onset.
-The physiological responses of the body to hypovolemic shock are aimed at maintenance of cerebral and coronary perfusion and improving the circulating blood volume. The major compenstory mechanisms include
- An increase in sympathetic activity
- Release of stress hormones and
- Volume improvement through restoration of interstitial fluid, mobilization of intracellular fluid, saving of fluids and electrolytes by the kidney.
The clinical picture reflects this intense adreno-sympathetic response and renal conservation of fluid.
-Micro-vascular low perfusion of some vascular beds of organs results from a combination of low intravascular blood volume, diminished cardiac output resulting from a reduction in venous return and preload, and compensatory vaso-constriction.*
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SHOCKING EFFECTS

2. LOCAL INJURY EFFECTS
2.1. The most significant effect of injury, to any part of the
body, is a decrease of circulating body fluid volume due to
-Blood loss,
-Edema fluid loss.

2.2. The tissues in the part that receives the physical injury
will initiate an inflammatory response.

2.3 Inflammation starts with an increased capillary permeability
in the injured area, resulting in exudation of the edema fluid in
the interstitial space.

2.4. If the injured part is considerable in size, there will be a
considerable retention of the fluid in this injured area creating
a third space, besides the intracellular and extra cellular spaces.

3. THE PERFUSION PUMP FACTORS
The principal central physiological factors that affect our
circulation is the following:-

3.1 Pre-load or the initial cardiac muscle fiber stretch, just
before contraction is an important determinant of cardiac muscle
functions (Starlings Law).
This is the end diastolic volume (filling) of the ventricle.

3.2 After-load. Cardiac function is affected by the
resistance, against which the heart muscle has to work in both
the pulmonary and systemic circuits.
This is the arterial resistance (pressure)

3.3 Contractility of cardiac muscle.
This is the reserve ability of the heart muscle to work efficiently
under conditions of pre-load and after-load.

3.4 Lastly it is the Heart rate.
The rate increases the cardiac output without increase in the
stroke volume.
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SHOCK- DEFINING MOMENTS

SHOCK
1. DEFINITION
The chief cause leading to shock is a lack of tissue
perfusion with oxygenated blood.
-Shock is low blood pressure, which is referred to as hypotension, but it also shows a continued inadequate tissue perfusion with O2.
-Thus the metabolic requirements of the tissues are not met.
-These requirements include supply of nutrients including O2, and removal of waste products.
1.1 If shock is treated in time cellular injury is limited.
1.2 If not treated irreversible widespread cell injury occurs
leading to multiple organ dysfunction and failure.

*Overview
-Shock is a clinical syndrome resulting from inadequate tissue perfusion.
-The decrease of delivery of requirement and the cellular unmet demand lead to cellular injury.
-Inadequate oxygen delivery is the main cause of shock states, the clinical manifestations of shock are caused by end organ dysfunction because of lower perfusion in spite of the body’s compensatory response.
-The continuing insufficient supply of oxygen to cells following sympathetic and neuron-endocrine interventions is cause of the symptoms and signs of shock.
-Timely restoration of perfusion and oxygen delivery usually reverse the shock state.
However the persistence or progression of shock may occur as a result of an ongoing undiagnosed perfusion defect or irreversible cellular injury, or a combination of the two phenomena.
-In addition, there is substantial clinical and laboratory evidence suggesting that cellular injury leads to production of pro-inflammatory chemical mediators that may further compromise perfusion through functional and structural changes in the microvasculature.
-This form of secondary injury further reduces perfusion, creating a vicious cycle of cellular injury leads to impaired perfusion that further increases cellular injury.
-Last in total body hypo-perfusion there is activation of potent inflammatory cells that may lead to the systemic inflammatory response syndrome (SIRS).
-It is suggested that persistence of SIRS, through the total body cellular dysfunction, may be the cause for the development of the multiple organ dysfunction syndrome (MODS).*

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BLOOD DOWNSIDE 2

7.3.2 HEPATITIS

Hepatitis B and C can be transmitted through blood transfusion.
Screening technique once again can increase the rate of detection
and cut the risk of transmission of the virus.

7.3.3 TRANSMISSION OF TROPICAL DISEASES
Malaria can also occur as a result of transfusion in our country. Donor screening procedures and history taking can limit this mode of transmission

7.4 MASSIVE TRANSFUSION

Changes are expected if more than 10 unit of blood are
transfused in 24 hours.
These effects are because of changes that occur in the blood
stored at 1 to 6oC in the blood bank.
-Leakage of intracellular Potassium from the RBC results in high
potassium in the plasma of stored blood.
-Decrease in pH and decrease in intracellular ATP also occur in stored blood.
-Affinity of RBC for oxygen (slow release of O2) and degeneration of white cells and platelets is observed in stored blood.
-There are also changes in clotting factor V and VIII leading to bleeding disorders.
-Blood stored for several days is devoid of functioning platelets. Therefore, there is dilutional thrombocytopenia

7.4.1 THERMAL LOAD

When large quantity of blood is transfused and blood is not
warmed there is excessive heat loss resulting in hypothermia.
Patient’s core temperature may fall below 34oc and the blood does
not clot normal.
Hypothermia slows citrate metabolism and reduces oxygen release by the hemoglobin

This effect can be counteracted if blood is warmed before
Transfusion.

7.4.2 ACID BASE CHANGES

There is usually alkalosis after massive transfusion.
Sodium citrate, (the anti-coagulant in the stored blood) is converted
into Sodium Bicarbonate in the liver.
The post transfusion pH may range from 7.48 to 7.50 and there is increased excretion of Potassium.

7.4.3 OTHER CHANGES DUE TO CITRATE

The citrate received with massive transfusion can also lead to
decreased level of calcium because the citrate binds ionized
calcium lowering the plasma calcium levels, this effects the
blood pressure (hypotension), narrowing pulse pressure, increase
central venous pressure.
The EGG shows a prolonged QT interval.

7.4.4 CHANGES IN POTASSIUM

This occurs because of leakage of potassium from the RBC into the
plasma.
This high potassium may cause rise in T waves in ECG.
In *association with hypocalcaemia this may alter cardiac
function.

7.4.5 HOMEOSTASIS
Massive transfusion leads to a decrease in a number of viable
platelets, since the stored blood has a very few platelets.
The platelet count may fall in cases of massive transfusion.
The PT and aPTT provides a reliable indicator for deciding whether FFP
is needed for the treatment of this effect.
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DOWNSIDE OF BLOOD FOR BLOOD

6. The Blood GROUPS

There are four types of groups:

1. Group A (red cells contain A agglutinogens, serum contain
Anti B agglutinins)
2. Group B (red cells contain B agglutinogens, serum contain
Anti A agglutinins)
3. Group AB (red cells contain both A and B agglutinogens,
serum contains no agglutinins)
4. Group O (red cells have no A or B agglutinogens, serum
contains both Anti A and Anti B agglutinins)

7. COMPLICATIONS OF TRANSFUSION

7.1 ABO Incompatibility

The most important complication resulting in loss of life is the
transfusion reaction, because of A, B, O incompatibility.
Most of these are events that result from clerical errors
-when the correct cross match has not been made or
-correct group had not been indicated on supplied blood.
In many cases the correct patient has not been
Identified in the ward.

These errors are preventable by installing ward and laboratory
procedures wherein no errors can occur.

When such transfusion reaction is suspected the transfusion should
be stopped and the urine be tested for Hemoglobin.
The blood bank should recheck the samples and record the event to identify the cause of the mismatch.

The patient should receive fluids to correct hypotension and
maintain renal blood flow.
Mannitol may be useful for diuresis.

7.2 IMMUNE REACTIONS

7.2.1 HEMOLYTIC

These reactions occur as a delayed reaction after the
transfusion has been completed.

-There is fall in hematocrit and it is accompanied by fever and
Jaundice.
-This jaundice may be caused by the antibodies to earlier
transfusions.
It may also be because of mishandled blood packs or infected blood packs.
7.2.2 NON-HEMOLYTIC REACTIONS

Erythma,
Urticaria,
Pruritus, occur within a few minutes of start
of transfusion.
-These are allergic reactions and the symptoms are due to release of Histamine and Serotonin as result of antigen-antibody reaction.
Transfusion is slowed down, and anti-histamine is given.
If no progress of symptoms occurs the transfusion can be continued.
7.2.3 ANAPHYLACTIC REACTION

The symptoms include

* Respiratory distress Bronchospasm
* Hypertension later Hypotension
* Subcutaneous edema

These are caused by antigen-antibody reaction and complement
activation and treated by:
1. Stop transfusion
2. Start isotonic saline
3. Anti-Histamine intravenously
4. Cortico-steroid 100 mg. hydrocortisone IV
5. Oxygen
6. Give diuretics eg. Furosemide. IV

7.3 TRANSMISSION OF DISEASE

Viral and bacterial infection can be transmitted by blood
transfusion.
This is possible if proper screening procedures for
donors are not conducted.

7.3.1 HUMAN IMMUNODEFICIENCY VIRUS

If screening of donar for HIV is not conducted this virus can be
transmitted through blood transfusion.

Awareness of prevalence of HIV in the population and screening
Procedure will bring down this mode of transmission.
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BLOOD FOR BLOOD

5. BLOOD TRANSFUSION

The varieties of hemorrhages have been dealt with in detail in chapter on Shock(Chap3).
We need to discuss here some clinical methods for assessing the
amount of blood loss so as to start treatment.

To estimate blood loss in the ward or emergency room:

* Swabs can be counted and weighed to estimate blood loss
* The clots can also be weighed to calculate blood lost
* In closed wounds, a moderate swelling in the leg may indicate
a loss of 1000-1500 cc of blood
* A similar swelling in the thigh (fracture femur) may
indicate a loss of 1000-2000cc
* Fracture pelvis may indicate a loss of >2000cc

Blood loss of <20% need not be replaced with whole blood.
-Immediate circulating fluid needs are provided by the transfer of fluid from the extra-vascular compartments.
-Protein lost in the blood is replaced by the body protiens in days
-RBC are replaced in weeks.

-Blood loss of 20-25% can be replaced by saline,
-loss of 30-35% may require replacement with plasma substitutes.
-When loss of 50% or more occurs replacement with whole stored blood is
required.

BLOOD is required in all cases of acute blood loss:

* Trauma + haemorrhage-(fracture)
* Intra-operative
* Post-operative
* In cases of deep burns
* In cases of bleeding disorders

5.1 HOMOLOGUS BLOOD

Stored blood is obtained from donors and kept in bags of 300cc.
Each donor needs to be carefully screened to limit the risk of
transmission of disease to the recipient.

5.2 AUTOLOGOUS BLOOD

Patient can donate his own blood within 5 weeks prior to the
surgery.
This blood can then be used at the time of surgery.
Blood lost during surgery can also be collected at that time
Washed, filtered and re-infused.

5.3 Blood Grouping and Cross Matching
Transfusion of blood require arrangements with the blood
bank
-to group patient's blood and
-cross match sample of blood
with sample of the same group in the blood bank.

-For this purpose a sample of blood has to be obtained from the
patient.
-All red cells contain agglutinogens (A and B).
-The serum contains Agglutinins (Anti A and Anti B).

5.4 Rh Factors
This is an antigen found in Red Cells and human red cells can be
either Rh+ or-.
Antibodies in the serum develop if Rh positive cells are
injected in Rh negative.
At the 1st repeat transfusion no problem may arise but subsequently
transfusion may produce Haemolysis.
Approximately 85% of the population is Rh positive.

Before transfusion the red cells of the donor (stored blood) are
matched against the serum of the recipient (the patient)
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BLOOD SPIN-OFFS FOR BLEEDING

LAB-INDICATORS-ACTION PLAN


Platelets must be counted in the blood if normal, we proceed to the tests that follow

3. TEST IN BLEEDING DISORDERS



3.1 BLEEDING TIME

This tests platelet and vessel wall interaction plus plug
formation.
This may be increased in thrombocytopenia, altered
Platelet function, Von Will brands disease factor V deficiency
and hypofibrinogenaemia .
It should not exceed 3-5 minutes.

3.2 PROTHROMBIN TIME

This test measures the efficiency of the extrinsic pathway.
Tissue source thromboplastin and calcium are added to citrated
plasma and the clotting time noted.

3.3 PARTIAL PROTHROMBIN TIME

This is a screening test for assessing the intrinsic pathway.
The range of normal varies and has to be compared with normal
control.

THROMBIN TIME (TT)

3.4 Tests Fibrinogen activity

The clotting time of patients’ plasma following addition of
standard controls are run.
Failure of clotting is evidence of low finbrinogen.
Excessive fibrinolysis can also prolong the thrombin time.




4 BLOOD COMPONENTS IN CLINICAL USE

4.1 PLATELET RICH PLASMA (PRP)

This is prepared by slow centrifugation of fresh whole blood.
Platelet concentrate is prepared by centrifuging PRP at 1500 rpm
for 20 minutes.
It can be stored and the platelet activity is preserved for seven days.

Platelets transfusions are indicated in cases of

* Thrombocytopenia
* Altered platelet functions

In general, platelets should not be given unless:

* There is micro vascular bleeding
* Patient of low count is for surgery
* Platelet count falls to below 10,000

After each unit, platelet count should rise by 5000/cmm at 1
hour.

4.2 Leukocyte concentrate

This is indicated in patients with granulocytopenia (<500/mm)
patient with infection (blood culture positive) with no response
to antibiotics.
Daily transfusions are required till counts exceed 1000/cmm.

4.3 Fresh Frozen Plasma (FFP)

This is normal plasma containing Citrate and is used in liver
disease and DIC.
This is indicated in a number of cases of coagulopathies with
proven deficiency of clotting factors.
This may be met with in:

* Liver dysfunction
* Congenital disorders
* Transfusion related deficiency

In cases of investigation documented factor deficienies.
Alternatives used are albumin, hetastarch.

4.4 Cryoprecipitate

If frozen plasma is brought to a temperature of 4oC white
Cryoprecipitate will seperate out.
This is rich in factor VIII and can be stored at -40oC.

The concentrate contains factor VII, fibrinogen, vWF.

This is indicated in Hemophilia, Von Wilhbrand's disease
Hypofibrinogenemia.
It may also help to treat uremia bleeding and DIC.

4.5 Packed RBC

A stable asymptomatic patient should not receive transfusion only
because haematocrit is below 30%.
Each unit of packed cell raises haematocrit by 2-3%

4.6 Washed RBC

Are indicated in patients who cannot tolerate plasma, leucocytes
and platelet debris.
These are patients with fever or renal failure

4.7 Deglycerised RBC

Deglycerised RBCs of rare blood groups can be stored for 3 years
at -65oC.
When they are required they are thawed, washed and transfused.
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BLEEDING IN OTHER DISORDERS

2.4.2 RENAL FAILURE

Uraemia causes reversible bleeding disorder related to platelet
dysfunction.
There is as a result reduced platlet aggregation and adhesion.
There is also a reduction in platlets factor II and prolonged bleeding time.

The intravenous adminstration of desmopressin 0.3 ug/kg helps to
stop bleeding.
Cryoprecptitate also help to control the bleeding disorders.
Conjugated estrogens also of use in uremia bleeding disorders.

A vast number of etiologic agents have been identified here and
must be kept in mind when a patient presents with a bleeding
tendency.

**Acquired Disorders
Vitamin K deficiency
The causes of vitamin K deficiency are many.
Dietary intake may be poor, or the intake may be adequate but malabsorbed.
Vitamin K is a fat soluble vitamin, so any factor that causes decreased fat emulsification by bile salts can lead to malabsorption (e.g. biliary obstruction, decreased bile salt formation cholestasis, biliary fistula).

Antibiotic causes include oral antibiotics that can kill vitamin K producing bacteria in the gut, or cephalosporin antibiotics containing the N methylthiotetrazole side chain (e.g. cefoperazone, cefotaxime, cefamandole, moxalactam).

Other etiologies include parenteral alimentation without vitamin K supplementation, renal insufficiency, and hepatic dysfunction.

Vitamin K is a necessary cofactor in the y-carboxylation of glutamate residues of factors II, VII, IX and X as well as protein C and protein S. As these factors are referred to as the vatimin K-dependent factors. Without vitamin K, these coagulants cannot bind calcium properly and thus are not active.

Treatment
Vitamin K may be given orally or parenterally to correct coagulopathy form deficiency or to reverse the effects of warfarin.

Anticoagulant Drugs

Drugs that affect hemostasis are abundant and their numbers increase each year. More detailed information on hemoactive durgs can be found later in this chapter.
I Thrombocytopenia
Thrombocytopenia is generally defined as a platelet count less than 100,000/mm3 .

Bleeding is more common after surgery or injury in cases with counts from 50,000 to 100,000 mm3

Spontaneous bleeding usually does occurs with count below 20,000 and is common with count below 10,000.
The etiology of thromboeytopenia may be
- Decreased production of platelets
- Increased use, consumption or sequestration of platelets;
- Dilution

Decreased production may occur with various oncologic disorders or after chemotherapy. Consumption of platelets may occur in sepsis, disseminated intravascular coagulation (DIC), or thrombotic thrombocytopenic purpura, and sequestration can occur in the spleen.

Dilutional thrombocytopenia is possible after massive transfusion.

Many drugs can cause thrombocytopenia through an immune mechanism, antibodies are formed to platelet glycoproteins. These drugs are quinidine, sulfa drugs histamine antagonists oral hypoglycemies, gold salts, rifarnpin, and heparin.

The most common of these is heparin.
Chronic alcohol consumption may lead to alcohol induced thrombocytopenia.

Clinical
Clinical manifestations of thrombocytopenia include cutaneous petechiae or purpura, cucosal bleeding, easy bruising, and excessive bleeding after surgery or injury.

Treatment
Management involves correcting or reversing the underlying cause if found. Transfusion of platelet concentrates is indicated for active bleeding associated with thrombocytopenia, and to keep platelet counts above 10,000 to 20,000/ mm3.

If an invasive procedure or surgery is necessary in a thrombocytopenic patient, transfusion is most beneficial in providing hemostasis when given just before or during the procedure.

Multiple platelet transfusions often lead to formation of alloantibodies, thus decreasing the efficacy of repeated administration. Platelet transfusion is not indicated for empiric or prophylactic treatment during massive transfusion or resuscitation, unless there is clinical evidence of microvascular bleeding, or a prolonged bleeding time.**
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DIC BY ANOTHER NAME

Consumptive Coagulopathy (PATH PHYSIOLOGY)


EVENTS LEADING TO THE EVENTS



**In certain conditions, bleeding is caused by a decrease is platelets and / or coagulation factors resulting from their USE UP in the blood vessels, a condition known as consumptive coagulopathy. Also called DIC
Rapid fibrin deposition occurs, decreasing the fibrinogen level, and also platelets due to trapping causing thromboeytopenia.
There is recent data showing that the receptor on the liver hapatocytes are responsible for
Depleting platelets and other factors.
Hypofibrinogenemia concurrent with thrombocytopenia in a bleeding patient is good evidence for a consumptive coagulopathy.
Fibrinolysis is induced, resulting in increased fibrin degradation products in the blood.
There are many etiologies of consumptive coagulopathy, with the principle example being the syndrome of DIC. The distinction between DIC and the other etiologic conditions listed below is ill defined, and one or more of the processes may be overlapping.
1. Sepsis. These conditions are a common cause of postoperabive thrombocytopenia. The mechanism is unclear, may is part be due to endotoxin-induced aggregation and destruction of platelets in the microvasculature or by direct activation of the coagulation cascade.
Also APC is deficient and so formation of microthrombi is not inhibited.
2. Shock, Trauma, Burns, and Pancreatitis.
These conditions cause release of thromboplastic substance that increase thrombin formation and consumption of coagulation factors. They also can lead to thrombocytopenia. In addition, inadequate tissue perfusion incites the inflammatory response, which leads to coagulopathy.
3. Traumatic Brain Injury. Injured brain tissue releases its rich stores of thromboplastin, which leads to hypercoagulability by accelerating fibrin formation and microvascular thrombosis. Coagulation sustrates are consumed and further clotting is impaired.
4. Obstetric Emergencies. Placental abruption, amniotic fluid embolism, dead fetus, eclampsia, septic abortion, and hydatidiform mole all can cause release of thromboplastic substances that increase thrombin formation and consumption of coagulation factors.
5. Disseminated Intravascular Coagulation. DIC is an acquired coagulation disorder that involves diffuse activation of the coagulation system, with fibrin deposition in the microvasculature, platelet aggregation, and thrombosis.
The severity ranges from subelinical or low grade to serve and life threatening.
Clinically DIC is manifested by generalized bleeding, and end-organ failure results form the diffuse microvascular thrombosis.
The more severe form can lead to multiple organ system failure and death. Mortality is increased in septic or severely injured patients with DIC.
A variety of clinical conditions are associated with DIC. In addition to all of the process listed 1 to 4 DIC may be associated with massive transfusion, hemolysis liver discase, and malignancy (including leukemis).
The pathophysiologic process in DIC is limited through inflammatory mechanisms and cytokines, especially interleukin-6.
The systemic formation of fibrin results form three mechanisms.
-First TF activated factor VII, and the TF factor VIIa complex mediates formation of thrombin, with subsequent conversion of fibrinogen to fibrin and activation of platelets.
-Second, the natural anticoagulant mechanisms operating via antithrombin III (ATIII), protein C and TF pathway inhibitor all are impaired in DIC. This leads to a shift in the hemostatic balance toward thrombosis.
-Finally, fibrin clearance is decreased because of a relative excess of PAI-I(plasmin activator inhibiter), which inhibits plasmin formation and fibrinolysis.
Diagnosis of DIC is made by the combination of clinical finding and certain supportive laboatory tests. There is no specific test that confirms or rules out the diagnosis. Clinically one suspects DIC in paitents with a generalized coagulopathy, bleeding and the presence of an inciting factor or disease associated with DIC.
The patient usually has a low or decreasing platelet count and prolonged PF/PTT. FSPs may be present in the plasma and coagulation inhibitors such as ATIII may be deficient.
Fibrinogen levels may be low in severe DIC, but, because fibrinogen is an acute phase reactant, its production is increased as part of the stress response, and levels may be normal.
The D-dimer assay is the most sensitive test for DIC, being abnormal in up to 94% of patients with a diagnosis of DIC.
In many patients with coagulopathy who are suspected of having DIC, hypothermia needs to be considered as the primary etiology of the bleeding disorder, especially if sepsis is not present.

Treatment of DIC
Treatment is of the underlying disease process is essential.
Symptomatic treatment can be tried but is futile if the underlying disease is not treated at the same time.
Several specific strategies have been investigated as therapy of DIC.
Anticoagulation has been used as an attempt to halt the underlying hypercoagulation in DIC.
Currently there have been no controlled studies showing any benefit of.**

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COAGULATION SYSTEM BREAKDOWN

SYSTEM OVERLOAD
2.4.1 Disseminated Intravascular Coagulation (DIC).
This syndrome is a systemic Thrombo-hemorrhagic disorder.
It occurs in small vessels (micro vascular) or sometimes in large vessels, and can leads to organ failure and death.
It is met with as a mild or severe form in the following conditions:
* Hemolytic
* Gram positive or gram negative sepsis
* Viremia
* Crush injury
* Burns
* Leukemia
* Malignancy with Metastasis
2.4.2 Clinical features
In DIC there is evidence of coagulation activation, fibrinolytic
activation, inhibiter consumption resulting in biochemical
evidence of some end organ damage.

In low grade DIC, there are minimal symptoms and laboratory
evidence while in severe DIC there is life threatening bleeding
disorders.

The simultaneous activation of coagulation and fibrinolytic
systems results in presence of both thrombin, and plasmin in
circulation.

Thrombin alters fibrinogen and fibrin monomers are released.
These cause fibrin clots resulting in microvascular thrombosis.
Platelets are entrapped in Thrombus leading to their depletion in
the blood.
Plasmin in circulation further acts on the degraded products in circulation, resulting in depressed levels of fibrinogen and increased levels of fibrinogen degradation products.
Plasmin also degrades factor V, VIII, IX and XI and
activates complement system all these derangements lead to D
**Fibrinolysis (and Regulation of Thrombosis)

-The fobrinolytic system aims to break down fibrin and dissolve thrombus, allowing healing of the wound. If provides a to limit the thrombotic mechanism.
-The main means for fibrinolysis is the breakdown of fibrin into soluble fragments by the proteolytic enzyme plasmin.
-Plasmin binds fibrin, and splits it at multiple sites, resulting in fibrin split products (FSPs)
The process Steps.
-Plasminogen is the precursor to plasmin. It is converted to plasmin by tissue plasminogen activator (tPA), which is released form endothelial cells near the site of injury.
-Although this reaction is inefficient in the general circulation, in the presence of a fibrin clot it is rapid.
-Thus fibrin is both the target and controler of its own destruction. Urokinase, so named because of its high concentration in the urine, is a plasminogen activator that is not fibrin specific.
-That, it converts plasminogen to plasmin in the circulation and not just on the clot.
-It is also the main activator of fibrinolysis in the extravaseular space.
-Urokinase is formed form the singlechain urokinase plasminogen activator precursor.
-Alpha2 antiplasmin (alpha2-AP) is the main inhihitor of plasmin, but also can bind plasminogen.
-Plasmin is inhibited by alpha2-AP when in the circulation, but its degradation is prevented when bound to the fibrin clot.
-This ensures localized, and not systemic, fibrinolysis.
-Fibrinolysis is kept in check by several inhibitors of plasminogen activation.
-These include plasminogen activator inhibitor type I (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI).**

Lab. Diagnosis
- No test confirm fibriolysis, but the process can be assed by laboratory tests
- One can measure levels of fibrinogen.
- FSPs,
- Plasminogen
- Plasminogen activator and
- Plasimin inhibitors
- The thrombin time (TT) is prolonged in fibrinolysis, and is useful in monitoring the fibrinolytic state during fibrinolytic therapy.
- Bleeding complications from such therapy are more common when the fibrinogen level is less than 100mg/dL and when FSPs are greater the 100U/dL,

Treatment
- Fresh frozen plasma (FFP) can be used to correct fibrinogen levels and reduce coagulopathy in such situations**.

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THE CASCADE EVENTS

**Hemostasis(BASIC SCIENCES)
THE STEPS AND SEQUENCE


Hemostasis is a process of linked physiologic events aimed at limiting of bleeding. It can be divided into two broad stages.

Primary and secondary hemostasis.
-Primary hemostasis involves the initial clot formation by adherence of platelets to the damaged blood vessel wall.
-Secondary hemostasis includes initiation of the coagulation cascade thrombin generation, and fibrin deposition.
Steps
-The main partners of primary hemostasis are platelets and endothelial cells. Platelets are 1.5 to 3.5µm discoid blood cells without nucleus or DNA that are formed from bone marrow megakaryocytes.
-Their key structure are their secretory granules, contractile cytoskeleton, and outer proteoglycan coat, which contains membrane receptors.
-The intracellular granules are of two types, alpha granules and dense granules (or dense bodies).
-Alphgranules contain platelet thrombospoundin, fibrinogen, fibronectin, platelet factor 4, von Willebrand’s facto (vWf), platelet derived growth factor (PDGF), factors V, X and VIII, and many other.
-Proteins dense granules contain ATP, ADP, GTP, GDP, other phosphates, calcium and serotonin.
-After platelet activation, these contents are released the presence of platelet specific proteins in the serum is the start of platelet activation.
-The endothelium is recognized as a metabolically active tissue that plays a role in coagulation and inflammation.
-The normal endothelium functions to maintain a nonthrombogenic surface in normal blood vessels, and keep a balanced steady state between the continuous process of coagulation and fibrinolysis. --Although the normal endothelium is nonthrombogenic, it secretes a subendothelial matrix gets exposed to the plasma (with break of endothelium), acts as highly thrombogenic.
-Another function of the endothelium (and megakaryocytes) is production of vWf. Stores of vWf are released into the subendothelium when the endothelium is damaged.
This initiates platelet, adhesion, leading to degranulation and further adhesion. Primary hemostasis is further enhanced by the initial vasoeonstriction of the damaged vessels.

Secondary Hemostasis:
Coagulation Cascade
Steps
-Following the initiation of the primary hemostatic process the coagulation cascade is activated which ends with the formation of a stable fibrin clot. Inactive forms of factors in the blood are converted to their active forms and this leads to a cascade effect with progressively larger amounts of coagulation factors produced.
-Fibrin monomers are generated as the final product of this cascade and are physically cross-linked to form the final stable clot.
-Normal state coagulation involves the interaction of many factors and is limited to the vessel wall injured.
This occurs through a series of inhibitory and regulatory substances, with their feedback loops.
The diluting effect of the blood flowing through the affected area is also a factor.
Till now coagulation has been understood to involve two “pathways” intrinsic and extrinsic.
-The intrinsic pathway did not require interaction with the injured vessel wall and resulted in the activation of factor XII as the initiating event for coagulation.
-Activated factor XII then activated factor XI, which in turn activated factor IX. A complex of activated factor VIII (factor VIIIa) and activated factor IX (Factor IXa) with calcium and phospholipid then activated factor X.
-Activated factor X (Factor Xa) then converted prothrombin to thrombin, which in turn converted fibrinogen to fibrin.
-Factor XIIIa converted the fibrin monomers into a cross-linked fibrin clot in the presence of calcium.
In the extrinsic pathway, coagulation is initiated when circulating factor VII interacts with subendothelial tissue factor (TF) in the presence of calcium. Subendothelial TF is exposed to the circulation as a result of endothelial injury.
-The activated factor VII (factor VIIa) TF complex activated factor X. Factor Xa then converts prothrombin to thrombin, and the reaction proceeds as described previously to generate a stable fibrin clot.
It is now felt that the
-The intrinsic pathway play a minor role. Inadequate levels of some of its key components will render standard coagulation tests abnormal but do not result in a clinically significant bleeding disorder.
-However the importance of the TF pathway as the predominant mechanism for in vivo coagulation is supported by recent research.
-The distribution of TF in the subendothelial layer, the epidermis, and myoepithelial cells.
-Thus the intact cells constitutes a “hemostatic barrier”.
-Injury puts TF into contact with factor VII, thus initiating coagulation.
-This concept of a single coagulation pathway (TF pathway) fits with current data and observed clinical syndromes and should replace the older concept of twin pathways**
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THE CASCADE

FLOW CHART OF CAGULATION EVENTS


HOMEOSTASIS 3

THE FACTORS AND THE PATH
As stated earlier the process of coagulation may be initiated by intrinsic cause
or by extrinsic causes
The factors involved and there interactions are shown in Fig. 2.1.
The factors are Named and the deficiency management is tabulated in Table 2.1 below.

Intrinsic Path
(Present in Blood)
XII--------------
? HMWK *

XIIa
XI--------------


XIa
IX------------- Extrinsic Path
ca2+ (Outside the blood vessel)
Present in Tissue Protein
IXa------ -------
ca2+ ca2+
Phospholipid VIII Tissue Thromboplastin

X-----------------------
Phospholipid ca2+
V

Xa
Prothrombin---------------


Thrombin
Fibrinogen---------------------> Fibrin

ca2+ XI

Firm clot

* High Molecular weight Kininogen

Fig. 2.1 COAGULATION CASCADE AND FACTORS REQUIRED
BMJ 1997 314 1026


Factors that take part in these mechanisms are named and listed
in Table 2.1.
TABLE 2.1
NOMENCLATURE OF COAGULATION FACTORS
_______________________________________________________________________

FACTOR SYNONYM TREATMENT DEFECIENCY STATES
_______________________________________________________________________
I Fibrinogen FFP,cryoprecipitate platelet
II Prothrombin FFP, Platlets
III Thromboplastin (tissue
factors)
IV Calcium ion
V Proacclerin,labile factor FFP,minimal in platelets
vWF Von Willebrand's factor FFP,cryoprecipitate,full
concentrate
VII Serum prothrombin conversion FFP, Platelets
accelerator, stable factor
VIII Antihemophilic Factor A FFP,cryoprecipitate,factor
VIII concentrate(plasma
derived or recombinant)
*IX Christmas factor FFP,prothrombin complex
concentrate,factor IX
concentrate,platelets
*X Suart-Power factor FFP,Platelets
XI Plasma thromboplastin FFP,minimal in platelets
antecedent
XII Hageman factor FFP, platelets
XIII Fibrin Stabilizing factor
Low Platelets counts Platelets
_______________________________________________________________________
* Vitamin K-dependent factors
FFP Fresh frozen plasma, platelet packs
The mechanism involved in the intrinsic process of coagulation
are initiated by inactive factor XII coming in contact with
factor VII to form a complex which activates factor X.
Then onwards the process follows a common pathway ending with the
production of fibrin.
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BLOOD A LIVING TISSUE

HEMOSTASIS 2

**Red Blood Cell Life and death

The red blood cell does not possess the structures required for DNA synthesis nor, for transcription and translation of proteins.
Cellular life depends on the cell’s ability to generate ATP through the utilization of glucose. Without the pathway for ATP generation, the cell would not be able to maintain its membrane integrity, and ionic gradients.
The ability to maintain hemoglobin in its reduced form for the transport and delivery of oxygen would also be limited.
Glucose is the primary fuel of the erythrocyte. It enters the cell through diffusion from the plasma, and through glycolysis ultimately is converted to lactate and pyruvate.
This process uses 2 moles of ATP and produces 4 moles of ATP, for a net gain of 2 ATP molecules.
The rate limiting step is controlled by the activity of phosphofructokinase, which converts fructose 6-phosphate to fructose 1,6 phosphate. This enzyme is inhibited by high concentrations of ATP, which signal the “fed” state.
Conversely, high concentrations of AMP signal an “energy starved” state favouring continued glycolysis.
The energy generated by glycolysis is utilized by the Na+ -K+ ATPase pump to regulate cell membrance potentials.
Maintenance of the appropriate redox potential is essential for the red blood cell to complete its function of oxygen delivery.
The red cell ultimately dies as its enzyme systema burn out.
The inability to continue glycolysis to maintain membrane gradients leads to changes in membrane permability and ultimately to cell destruction.
More than 90% of red cells with altered membrane are destroyed by the macrophages of the reticuloendothelial system (spleen, liver and marrow).
As the cells are destroyed, the hemoglobin molecule is further degraded. The iron is largely conserved, redistributed to the marrow, and incorporated into new hemoglobin**

1. Coagulation

1.1 Intrinsic
In all injuries, there is injury to blood vessels with the
resulting exposure of blood to tissue factors and collagen in the
injured wall of the blood vessels factors V and VIII are
available in the endothelium.
There follows as a result platelet aggregation and adherence with formation of a plug at the injury
site.

Hemostasis(control of bleeding) is achieved within the body by four events occurring in
sequence:

* Vessel wall smooth muscle constriction at the site of injury
Vasoconstriction limits the blood loss. This occurs in
response to release of Thromboxane A and Serotonin from the
platelets. Endothalin is also responsible and is released
from the endothelial cells.
* Platelet function. The platelets adhere to one another and
also to the vessel wall at the site of injury to form a plug
* Coagulation wherein prothrombin is converted to thrombin and
their product in turn converts fibrinogen to fibrin
improves the platelet plug
* Fibrinolysis. This process causes the lysis of the fibrin
to restore the patency of the blood vessel.
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