Lecture 4

General Pathology 2022

Derangement of homeostasis and

hemodynamics I
Prepared by: Gran Omer – Hussen Hirmz-
Lawez Araz – Mohammed Taha-
Rezheen Aryan
 Homeostasis
The term internal environment or milieu interieur for the state in the body in which the interstitial fluid
that bathes the cells and the plasma, together maintain the normal morphology and function of the cells
and tissues of the body. The mechanism by which the constancy of the internal environment is
maintained and ensured is called the homeostasis. For this purpose, living membranes with varying
permeabilities such as vascular endothelium and the cell wall play important role in exchange of fluids,
electrolytes, nutrients and metabolites across the compartments of body fluids.
Homeostasis:- stable internal condition or maintaining the normal morphology and function of cells and
tissues.

• The range of female water is 1, it is lower than in male because of presence of higher amount of fat
in female
• The majority of the body parts are composed of fluids. These fluids are present in the form of
intracellular compartments within the cytosol of the cytoplasm of the cells, in the interstitial tissues,
and cardiovascular system (in the form of blood; plasma is the liquid part).
• The presence of fluid is very important in order to regulate the normal physiological functions &
morphology of the cells. The process by which cells provide microenvironments are via a
phenomenon is called homeostasis.
• Homeostasis is important in regulating the normal physiological functioning of cells in our body. If any
change occurs in the amount of fluid present inside the cytosol, interstitial tissues, or cardiovascular
system; it will probably affect the normal physiological functioning of the targeted cell, tissue, or
organ.
The normal composition of internal environment consists of the following components:
I. WATER. Water is the principal and essential constituent of the body. The total body water
in a normal adult male comprises 50-70% (average 60%) of the body weight and about
10% less in a normal adult female (average 50%). The total body water is distributed into
2 main compartments of body fluids separated from each other by membranes freely
permeable to water.
i. Intracellular fluid compartment. (contained in muscles)
This comprises about 33% of the
body weight, the bulk of which is
contained in the muscles.
ii. Extracellular fluid compartment (contained in water)
This constitutes the
remaining 27% of body weight
containing water.
• In general, when we talk about fluid, it is mainly composed of water. Around 50% to 70% of the body
weight of an adult, with differences between the male & female water-level amounts, is composed of
water.
• Q/ why is the amount of fluid in the body of females less compared to the amount in males?
• On average, 60% of the male body weight is made of water, while only around 50%, on average, in
females. 33% of this amount (water) is present as intracellular fluid compartment, within the cytosol
of the cytoplasm of the cells. The remaining 27% is present as an extracellular fluid compartment,
5% of which is present in the form of blood plasma, 12% of which is present in the interstitial tissues,
and the remaining 10% as others.
• In men, 60% of their bodies are water. However, females does not have as much water so in women,
so fat makes up more of the body than men and also fat contains less water, so they have about
55% of their bodies made of water.
 II. ELECTROLYTES. (different ions Mg,K,Ca)
The concentration of cations (positively charged) and anions (negatively charged) is
different in intracellular and extracellular fluids: i. In the intracellular fluid, the main cations
are potassium and magnesium and the main anions are phosphates and proteins. It has low
concentration of sodium and chloride. ii. In the extracellular fluid, the predominant cation is
sodium and the principal anions are chloride and bicarbonate. Besides these, a small
proportion of non-diffusible proteins and some diffusible nutrients and metabolites such as
glucose and urea are present in the ECF.

• Besides water, fluids contain electrolytes. Electrolytes are important in regulating the process of material

exchange and the normal physiological functioning of the cells. Electrolytes are present in the forms of positively

& negatively-charged ions. Different types of ions are present, the most important of which, are the sodium,

potassium, magnesium, calcium, bicarbonate, and chloride.

 Disturbances of body fluids
Oedema
The Greek word oidema means swelling. Oedema may be defined as abnormal and excessive
accumulation of “free fluid” in the interstitial tissue spaces and serous cavities. The presence of
abnormal collection of fluid within the cell is sometimes called intracellular oedema but should more
appropriately be called hydropic degeneration
Free fluid in body cavities: Depending upon the body cavity in which the fluid accumulates, it is
correspondingly known as ascites (if in the peritoneal cavity), hydrothorax or pleural effusion (if in
the pleural cavity), and hydropericardium or pericardial effusion (if in the pericardial cavity). Free
fluid in interstitial space: The oedema fluid lies free in the interstitial space between the cells and
can be displaced from one place to another.
In the case of oedema in the subcutaneous tissues, momentary pressure of finger produces a depression
known as pitting oedema. The other variety is non-pitting or solid oedema in which no pitting is
produced on pressure e.g. in myxoedema, elephantiasis.
The oedema may be of 2 main types:
1. Localised when limited to an organ or limb e.g.
lymphatic oedema, inflammatory oedema, allergic
oedema.
2. Generalised (anasarca or dropsy) when it is
systemic in distribution, particularly noticeable in
the subcutaneous tissues e.g. renal oedema, cardiac
oedema, nutritional oedema.
Depending upon fluid composition, oedema fluid may be: transudate which is more
often the case, such as in oedema of cardiac and renal disease; or exudate such as in
inflammatory oedema.
• Changes in the amount of body fluid can possibly include an excessive amount of fluid accumulation abnormally as a local condition,
for instance, local edema, or it can be accumulated systemically as when fluids are accumulated in different parts causing what is
called a swelling. Besides this, sometimes the amount of fluid is decreased in our body, a condition which is called dehydration.
• One abnormality produced due disturbances in body fluid is an edema. Edema is the accumulation of fluids. Edema is possible to be
seen at the level of cells when large amounts of water are accumulated in the cytoplasm. As taken in the previous lectures, hydropic
change is a type of derangement possible to be seen during cell injury when an excessive amount of water is accumulated inside the
cytoplasm of the cell. This usually occurs due to disturbances in the exchange of sodium and potassium when too much sodium is
accumulated inside the cytoplasm, thus increasing the amount of water in the cytoplasm.
• Besides this, edema is possible to occur in the interstitial tissues when too much fluid is escaping from the blood vessels and different
factors have a role in increasing the rate of interstitial fluid escaping.
• Besides this, water is also possible to be accumulated in the cavities, for example in the peritoneal cavity, also called the ascites, the
Causes abdominal
hydrothorax, the plural cavity (pleural effusion), and hydro pericardium. swelling
• Free fluid in the interstitial space is also another location where fluid can be accumulated.
• In general, when fluid is accumulated in the subcutaneous tissues, we have two types of edemas.
• Pitting Edema: is usually produced when the fluid accumulated is mainly made from water, when pressing the edematous area with
your fingers, a form of pit/indentation is produced after the removal of the pressed finger.
• Non-Pitting Edema: is usually produced when the fluid accumulated is not mainly only made from water rather the accumulation of
proteins, and other debris, firmer & smoother when compared to the pitted-type of edema.
 Feature Transudate Exudate
Definition Filtrate of blood plasma without changes Oedema of inflamed tissue
in endothelial permeability associated with increased vascular permeability

Character Non-inflammatory oedema Inflammatory oedema

Protien content Low (less than 1 gm/dl); mainly albumin, High ( 2.5-3.5 gm/dl), readily coagulates due to high
low fibrinogen; hence no tendency to content of fibrinogen and other coagulation factors
coagulate

Glucose content Same as in plasma, why? Low (less than 60 mg/dl)

LDH < 0.6 > 0.6

Cells Few cells and cellular debri Many cells, inflammatory as well as parenchymal

Because in excaudate an excessive utilization by inflammatory cells and impairment of diffusion across the membrane lining pleural cavity occurs
 Generally, when talking about edema we have two types:
1. Localized Edema: possible to be seen when fluid is accumulated on a specific area of the body on any part of
the body.
2. Generalized Edema: possible to be seen when fluid is accumulated on different or most areas of the body.
• Depending on fluid composition, we have two types of edema:
1. Transudate Edema: usually produced as a result of the accumulation fluid mainly made of water. Therefore, it
is mainly made from water with minor amounts of proteins. There is no inflammation! The amount of sugar is
same as in the plasma. So, the glucose in the fluid which is accumulated in the interstitial tissues has the same
amount of glucose present inside the plasma. LDH is lower than 0.6.
2. Exudate Edema: usually produced as a result of the accumulation of fluid not only made from water. Besides
water, there are large amounts of proteins and inflammatory cells. Usually associated with inflammation. The
amount of glucose is lower than the amount of glucose presents normally in the plasma. Why in exudate
edema, the amount of glucose in the accumulated fluid is lower than the amount of glucose which is present in
the plasma? LDH is higher than 0.6 because LDH is one of the markers that increases in the body when the
extent of cell damage is increased. So having cell damage increases the amount of LDH in the body and thus
acts as an indicator of having a cell injury.
Pathogenesis of oedema
Oedema is caused by mechanisms that interfere with normal fluid balance of plasma,
interstitial fluid and lymph flow.
The following mechanisms may be operating singly or in combination to produce oedema:
1. Decreased plasma oncotic pressure
2. Increased capillary hydrostatic pressure
3. Lymphatic obstruction
4. Tissue factors (increased oncotic
pressure of interstitial fluid, and
decreased tissue tension)
5. Increased capillary permeability
6. Sodium and water retention.
• Edema is possible to occur as a result of many mechanisms.
1. Decreased Plasma Oncotic Pressure: in the blood vessels there are two types of pressure:
a. Oncotic Pressure: usually regulated by proteins normally present in the plasma such as albumin.
b. Hydrostatic Pressure: is produced as a result of fluid or plasma. So when blood circulates through the blood vessels it
will produce a pressure on the walls of the blood vessels.
• Disturbances in these two types of pressures will increase the rate of fluid escaping from the plasma into the interstitial spaces.
Oncotic pressure is possible to be decreased in cases where the amount of protein is decreased. For example, in hypoalbunimia
when the amount of proteins is decreased in the blood, hence the normal oncotic pressure is affected as a result. Conversely,
when the oncotic pressure is increased it will increase the rate of fluid escaping from the blood vessels into the outside.
2. Increased Hydrostatic Pressure: increases the rate of fluid escaping from the plasma into the outside. Hydrostatic pressure
is possible to be increased in case of venous blockages; when the veins are obstructed by any factor, too much blood is
accumulated which can probably increase the rate of hydrostatic pressure.
3. Lymphatic Obstruction: lymph vessels are responsible to transfer the excessive fluid from tissues and cell so any
obstructions of blockages whether it occurs in the lymphatic duct can probably affect the rate of excessive fluid drainage
4. Tissue Factors (Increased Oncotic Pressure of Interstitial Fluid, and Decreased Tissue Tension): when the fluid in
present in the interstitial tissue, the amount if regulated by the oncotic and hydrostatic pressures, therefore if any change
occurs in these two factors it will probably affect the amount of fluid from the plasma into the interstitial spaces.
5. Increased Capillary Permeability: for whatever reasons, if the cell membrane of blood vessel walls in the capillaries is
changed by any factors, it will increase the amount of fluid escape from the plasma into the interstitial spaces.
6. Sodium & Water Retention: retention of these two is another mechanism which is controlled by the kidney, sometimes, for
many reasons, and as a response to any conditions, the kidneys will try to decrease the amount of sodium and water excretion
into the outside of the body . So any retention of these two by the kidneys, for whatever reason, can probably affect and
increase the risks of edema.
• Types of edema due to abnormalities in some vital/visceral organs
1. Renal Oedema
Oedema in nephrotic syndrome. Since there is persistent and heavy proteinuria
(albuminuria) in nephrotic syndrome, there is hypoalbuminaemia causing decreased plasma
oncotic pressure resulting in severe generalised oedema (nephrotic oedema). The
hypoalbuminaemia causes fall in the
plasma volume activating renin-angiotensin
aldosterone mechanism which results in
retention of sodium and water, thus setting in a
vicious cycle which persists till the albuminuria
continues. Similar type of mechanism operates
in the pathogenesis of oedema in protein-losing
enteropathy, further confirming the role of
protein loss in the causation of oedema.

Pathway leading to systemic edema resulting from heart failure

renal failure, or reduced plasma osmotic pressure
Renal odema:- Renal Edema: is a type of edema which is produced as a result of renal dysfunction. In cases of
nephrotic syndrome, when too much of the albumin is excreted into the outside of the body, it will probably
decrease the rate or amount of albumin in the blood, this condition is called hypoalbunemia. Decreasing the
amount of albumin will probably affect the oncotic pressure; hence the oncotic pressure decreases, as a result of
excreting too much albumin into the outside of the body. This decrease in the amount of albumin will affect the
normal oncotic pressure, the oncotic pressure is decreased and then fluid can very easily escape from the blood
vessels into the interstitial spaces, by the effect of the hydrostatic pressure. This is one of the factors which can
increase the rate of edema. When the hypoalbunimia is decreased, despite changes in the oncotic pressure,
another mechanism is possible to be activated. This mechanism can again increase the rate of edema. This
mechanism is called renin-angiotensin-aldosterone; when the albumin is decreased, a signal in send to the kidney
to release renin, renin is increased into the blood vessels when can then activate the angiotensin, and the
angiotensin will activate the aldosterone and vasopressin, these two work to activate the process of sodium and
water retention since the vasopressin works as an antidiuretic. It will decrease the rate of filtration and the amount
of urine. When urine is decreased, it means that the process of excretion of water and sodium to the outside of the
To outside
body is decreased. So this was the process of sodium and water retention and this process is activated by the
kidney s an attempt to restore the amount of sodium and water in order to protect the volume of the blood. So renin
and angiotensin activation is possible to be activated due to the decrease in the amount of albumin.
• Why does liver cirrhosis cause hypoalbunemia? Because liver produces albumin and any failure in liver reduces albumin

production.
• If we take a look at this figure, it is a figure of cardiac edema which is produced as a result of heart failure. In
case of heart failures, renal blood flow is decreased. When the cardiac output is decreased, all body parts will
not be able to get enough blood and the renal is one of those organs. So when the blood supply into the kidneys
has decreased, it will activate the process of renin-angiotensin-aldosterone system as an attempt to restore the
volume of the blood. This will lead to the retention of sodium and water in an attempt to increase the normal
blood volume and this retention will increase the rate of edema. Plasma albumin, if decreased, can probably
affect the plasma. So, plasma albumin can be decreased as a result of malnutrition or hepatic abnormalities
(since albumin is produced by the liver); so when the liver is not able to work properly, it will affect the amount of
albumin. Albumin is possible to be decreased as a result of the nephrotic syndrome when too much albumin is
excreted. Therefore, all of these factors work to increase the rate of edema.
2. Cardiac Oedema (localized & generalized)
Generalized oedema develops in right-sided and congestive cardiac failure.
Pathogenesis of cardiac oedema is explained on the basis of the following
hypotheses.
a. Reduced cardiac output causes hypovolaemia which stimulates intrinsic-renal and
extra renal hormonal (renin angiotensin-aldosterone) mechanisms as well as ADH
secretion resulting in sodium and water retention and consequent oedema.
b. Due to heart failure, there is elevated central venous pressure which is transmitted
backward to the venous end of the capillaries, raising the capillary hydrostatic
pressure and consequent transudation; this is known as back pressure hypothesis.
c. Chronic hypoxia may injure the capillary wall causing increased capillary permeability
and result in oedema; this is called forward pressure hypothesis. However, this theory
lacks support since the oedema by this mechanism is exudate whereas the cardiac oedema
is typically transudate.
• In left heart failure, the changes are, however, different. There is venous congestion,
particularly in the lungs, so that pulmonary oedema develops rather than generalised
oedema (described below).
• Cardiac oedema is influenced by gravity and is thus characteristically dependent oedema
i.e. in an ambulatory patient it is on the lower extremities, while in a bed-ridden patient
oedema appears on the sacral and genital areas. The accumulation of fluid may also occur
in serous cavities.
• Cardiac oedema is another example, in general any abnormalities if it occur in normal function of the heart it will probably

increase the rate of oedema, for example: in case of heart failure when the heart won’t be able to pump blood so cardiac output is

decreased, decrease in the cardiac output will probably affect the risk of hypovolemia.

• So decreasing blood supply will affect many or almost all tissues and organs in the body of the targeted individual and this will

activate the process of (renin angiotensin- aldosterone) mechanism that I have mentioned in the last slide and it will also activate

process of antidiuretic hormone secretion.

• Antidiuretic hormone secretion like vasopressin is working to reduce the amount of water and sodium excretion as a result oedema is possible to

be seen.
Generalized oedema
• Another type of oedema is produced for example in case of right side heart failure, right side heart failure possible to occur, so

when the right side heart failure is occurred means the blood or venous blood is not normally taken and sent to the lung so in

case of right side heart failure too much blood is accumulated in the venous circulatory part, accumulation of the blood in veins

will make a backward pressure on the capillary and the process is called back pressure hypothesis. Right side of the heart is not

working as a result blood accumulated in the vein accumulation of the blood in the veins will make pressure on the capillaries and

this will increase the risk of hydrostatic pressure in the capillaries as a result too much fluid is escaping from the capillaries into

the interstitial spaces.

• Another type of oedema is possible to be produced as result of cardiac or heart failure is
pulmonary oedema.
Localized
• Pulmonary oedema is produced as a result of left side heart failure. Left side is responsible for
taking the blood from the lung, when the left side is affected by any factor and isn’t be able to
perform normal function, which means too much blood is accumulated in the lung,
accumulation of the blood in the lung will increase the rate of oedema and the type of oedema
which is produced in the lung is called pulmonary oedema.
• In general, oedema which is produced as a result of cardiac failure is affected by gravity and is
called dependent oedema, in case of cardiac failure in ambulatory patient the type of cardiac
oedema is usually seen or the oedema which is produced as a result of heart failure is most
commonly affect the lower extremities, and in bed ridden patients the type of oedema possible
to be seen in sacral and genital areas.
• So, this figure will summarize the mechanism which are possible to be activated during the cardiac oedema or the

oedema that is produced as a result of heart failure.

• 3 mechanisms possible to be activated 1- extrarenal hormonal 2- intrinsic renal 3- antidiuretic hormone (ADH)

mechanism

• These 3 mechanism are activated during cardiac output failure it will probably decrease the amount of blood

which is supposed to be circulating throughout the body to provide oxygen and nutrients, decreasing volume of

the blood it will activate (renin angiotensin- aldosterone) mechanism and make the process of the sodium and

water retention and will decrease the rate of GFR and as a result excretion of sodium is decreased, and beside
Glomerular Filteration rate
these ADH is activated which is also working to decrease water and sodium excretion as a result

• At the end of these mechanisms the sodium and water are dramatically increased in the body of targeted

individual and this will probably increase the rate of interstitial fluid and increase blood pressure at the same time.
Localized 3. Cerebral Oedema (happens due to damage to blood brain barrier)
Cerebral oedema or swelling of brain is the most threatening example of oedema. The mechanism of
fluid exchange in the brain differs from elsewhere in the body since there are no draining lymphatics
in the brain but instead, the function of fluid-electrolyte exchange is performed by the blood-brain
barrier located at the endothelial cells of the capillaries.

Cerebral oedema is another type which is very fatal and cerebral oedema is occurred when the damage is occurred

in the BBB.

-BBB as you know is responsible for regulating the process of fluid exchange between CNS and cardiovascular

system, so any abnormalities if its occur it will probably affect the accumulation of fluid in the brain and as we said

this is very fatal.

4. Pulmonary Oedema
 Acute pulmonary oedema is the most important form of local oedema as it causes serious functional impairment
but has special features. It differs from oedema elsewhere in that the fluid accumulation is not only in the tissue
space but also in the pulmonary alveoli.
Etiopathogenesis. The hydrostatic pressure in the pulmonary capillaries is much lower (average 10 mmHg).
Normally the plasma oncotic pressure is adequate to prevent the escape of fluid into the interstitial space and
hence lungs are normally free of oedema. Pulmonary oedema can result from either the elevation of pulmonary
hydrostatic pressure or the increased capillary permeability
Pulmonary oedema is another type of oedema which is possible to occur in the lung. Here pulmonary oedema differs from the other type
because the fluid is not only accumulated in the interstitial space, it also accumulates in the alveoli. If you have a look at this image you
will see the fluid is not only accumulated in the interstitial space, and accumulation in case when the alveoli permeability has changed
and the fluid is possible to escape from the blood into interstitial spaces and also the fluid is possible to be accumulated in the alveoli and
maybe alveolar oedema. Accumulation of the fluid in the alveoli will probably affect the normal breathing, and increase the rate of
tachypnea and many other abnormalities is possible to be seen in case of pulmonary oedema. Because as we said, in case of pulmonary
oedema the fluid is not only accumulated in interstitial spaces, beside this fluid will accumulate in alveolar spaces as well and increase
the rate of alveolar oedema, accumulation of the fluid in alveoli it will probably affect the process of gas exchange and this will increase
the rate of a many abnormalities.
 Dehydration
Dehydration is a state of pure deprivation of water leading to sodium retention and hence a
state of hypernatraemia. In other words, there is only loss of water but no loss of sodium.
Clinically, the patients present with intense thirst, mental confusion, fever, and oliguria. Etiology.
Pure water deficiency is less common than salt depletion but can occur in the following
conditions:
1. GI excretion: e.g, Severe vomitings and Diarrhoea
2. Renal excretion: e.g., Acute renal failure in diuretic phase and Extensive use of diuretics
3. Loss of blood and plasma: e.g., Severe injuries, severe burns
4. Loss through skin: e.g., Excessive perspiration and Hyperthermia
5. Accumulation in third space: e.g., Sudden development of ascitesand Acute intestinal
obstruction with accumulation of fluid in the bowel.
• Another type of abnormality which is possible to be seen at the disturbance of body fluids is Dehydration,
dehydration is a clinical condition where too much amount of the water is excreted into the outside of the body
and this condition possible to be seen in many or as a result for example:
• In case of GI excretion when too much fluid or water is excreted into outside of the body like in case of
diarrhea and vomiting.
• Renal excretion: e.g., Acute renal failure in diuretic phase and Extensive use of diuretics, diuretics are group
of drugs which is used to increase the rate of the urine, too much urine means too much water and sodium are
secreted into outside of the body
• Loss of blood and plasma: in case of burns and severe injury, too much blood is escaping to outside of the
body
• Loss through skin: e.g., Excessive perspiration and Hyperthermia
• Accumulation in third space: e.g., Sudden development of ascites and Acute intestinal, obstruction with
accumulation of fluid in the bowel.
• So abnormal accumulation of fluid in body cavities will increase the rate of dehydration.
 Disturbances of electrolytes

In health, for electrolyte homeostasis, the concentration of electrolytes in both intracellular and
extracellular compartments should be within normal limits. Normal serum levels of electrolytes
are maintained in the body by a careful balance of 4 processes: their intake, absorption,
distribution and excretion. Disturbance in any of these processes in diverse pathophysiologic
states may cause electrolyte imbalance. Among the important components in electrolyte
imbalance, abnormalities in serum levels of sodium (hypoand hypernatraemia), potassium
(hypo- and hyperkalaemia), calcium (hypo- and hypercalcaemia) and magnesium (hypoand
hypermagnesaemia) are clinically more important. It is beyond the scope of this book to delve
into this subject in detail.

→Electrolyte imbalance may be due to, intake, absorption, distribution and excretion
• Disturbances of the electrolyte is another abnormality of the clinical condition which is possible to be seen in case of when
the too much electrolytes are excreted or accumulated withing the body, normally the electrolytes there is balanced between
cytoplasm interstitial space and the amount of electrolytes which is needed to be present normally and the excess amount
needs to be excreted through kidney
• There are 4 mechanisms that need to be balanced in order to regulate the amount of the electrolytes inside the body, the
mechanism are intake of these electrolytes. Any change that occur in amount of electrolytes which are supposed to be taken
daily will probably affect the level of the electrolyte by increasing or decreasing the normal amount. Absorption is another
factor, because rate of electrolyte absorption can be increased or decreased. Distribution how this electrolytes are distributed
between cytoplasm and interstitial spaces and excretion which is regulated by kidney.
• So, any abnormality which if it is occur or any imbalance if it is occur in these 4 mechanisms it will probably affect the
amount of the electrolytes.
• Different medical terms are used to describe the condition where a specific electrolyte is decreased or increased, when the
sodium is decreased in the body it’s called hyponatremia. In Hypernatremia salt increase. A lot of factors have a role in
decreasing or increasing the amount of these ions.
• Hypokalemia X Hyperkalaemia. Many factors which are listed here have a role in increasing or decreasing the amount of
potassium.
 Haemodynamic derangements

The principles of blood flow are called

haemodynamics. Normal circulatory
function requires uninterrupted flow of
blood from the left ventricle to the farthest
capillaries in the body; return of blood
from systemic capillary network into the
right ventricle; and from the right ventricle
to the farthest pulmonary capillaries and
back to the left atrium.
There are three essential requirements to maintain normal blood flow and perfusion of tissues:
normal anatomic features, normal physiologic controls for blood flow, and normal
biochemical composition of the blood.
Derangements of blood flow or haemodynamic disturbances are considered under 2 broad
headings:
i. Disturbances in the volume of the circulating blood. These include: hyperaemia and
congestion, haemorrhage and shock.
ii. Circulatory disturbances of obstructive nature. These are: thrombosis, embolism,
ischaemia and infarction.
• Haemodynamic derangements, this term is used to describe a condition or abnormality which possible to be seen
in the normal blood circulation, so as you know there is a cardiovascular system in our body which is responsible
for circulating the blood throughout the body, and blood is important to transport the gasses and nutrients and
hormones and many other things , the flow needs to be uninterrupted any interruption of the normal flow of the
blood will probably affect the normal function of many organ, in general when we talk about Haemodynamic
derangements we have 3 points that need to be considered:
• First of all is the normal anatomic features; in order for the normal blood flow normal anatomic features need to
be present, any abnormality which is occur in the obstruction of the blood it will probably affect the flow of the
blood.
• Normal physiologic controls for blood flow which is another important point, the process of the blood flow which
is controlled by many mechanisms and by many organs so any disturbance if it occurs in this control it will
probably affect the rate of the blood flow.
• Biochemical composition of the blood, as you know the blood is made of plasma and cells and many other
structures, so any change if its occur in the amount of the blood cellular compartment or plasma or both of them
• In general, when we talk about the Hemodynamic disturbances two types of abnormalites are possible to be seen
which affect the process blood flow:
• One of them is the disturbance in the volume of the blood when the blood volume is decreased or increased
• And obstruction of the blood vessel, these two things are different from each other sometimes the volume of the
blood is in the normal range but a part of the body doesn’t be able to get enough amount of the blood why? –
• Because for example obstruction, in this lecture I’m going to talk about the first point which is the disturbance in
the volume of the blood, in the next lecture I’m going to talk about circulatory disturbances as a result of
obstruction.
Disturbances in the volume of circulating blood
1. Hyperaemia and congestion
Hyperaemia and congestion are the terms used
for localized increase in the volume of blood
within dilated vessels of an organ or tissue; the
increased volume from arterial and
arteriolar dilatation being referred to as
hyperaemia or active hyperaemia, whereas the
impaired venous drainage is called venous
congestion or passive hyperaemia. If the
condition develops rapidly it is called acute,
while more prolonged and gradual response is
known as chronic.
Active Hyperemia
The dilatation of arteries, arterioles and capillaries is effected either through sympathetic
neurogenic mechanism or via the release of vasoactive substances. The affected tissue or
organ is pink or red in appearance (erythema).
The examples of active hyperaemia are seen in the following conditions:
• Inflammation e.g. congested vessels in the walls of alveoli in pneumonia
• Blushing i.e. flushing of the skin of face in response to emotions
• Menopausal flush
• Muscular exercise
• High grade fever
• Goitre
• Arteriovenous malformations
Clinically, hyperaemia is characterized by redness and raised
temperature in the affected part.
-Regarding the Disturbances in the volume of circulating blood we have two terms Hyperaemia and congestion.
Normally the blood is circulating through the artery, capillary and vein , so any change occuring in the diameter of
blood vessels will probably affect the amount of the blood and the rate of blood flow and at the end will increase the
accumulation of the blood for example.
-Active hyperaemia is a condition which occurs due to the dilatation of artery and arterioles, when the artery or
Accumulation
arterioles are dilated, too much oxygenated blood are pumped and as a result the affected area the color is changed
to become more red and this is possible to be seen as a result of many conditions like:
• Inflammation e.g. congested vessels in the walls of alveoli in pneumonia
• Blushing i.e. flushing of the skin of face in response to emotions
• Menopausal flush
• Muscular exercise
• High grade fever
• Goiter (increased size of thyroid gland) Swelling of neck
• Arteriovenous malformations
Clinically, hyperaemia is characterized by redness and raised temperature in the affected part.
Passive Hyperaemia (Venous Congestion)
The dilatation of veins and capillaries due to impaired venous drainage results in passive
hyperaemia or venous congestion, commonly referred to as congestion. Congestion may be
acute or chronic, the latter being more common and called chronic venous congestion (CVC).
The affected tissue or organ is bluish in colour due to accumulation of venous blood
(cyanosis).
Obstruction to the venous outflow may be local or systemic. Accordingly, venous
congestion is of 2 types:
▪ Local venous congestion
▪ Systemic (General) venous congestion
⮚ Local venous congestion results from obstruction to the venous outflow from an organ or part
of the body e.g. portal venous obstruction in cirrhosis of the liver, outside pressure on the vessel
wall as occurs in tight bandage, plasters, tumours, pregnancy, hernia etc, or intraluminal
occlusion by thrombosis.

⮚ Systemic (General) venous congestion is engorgement of systemic veins e.g. in left-sided and
right-sided heart failure and diseases of the lungs which interfere with pulmonary blood flow
like pulmonary fibrosis, emphysema etc. Usually the fluid accumulates upstream to the specific
chamber of the heart which is initially affected. For example, in left-sided heart failure (such
as due to mechanical overload in aortic stenosis, or due to weakened left ventricular wall as in
myocardial infarction) pulmonary congestion results, whereas in right sided heart failure (such
as due to pulmonary stenosis or pulmonary hypertension) systemic venous congestion results.
Passive hyperaemia (venous congestion):
Xwen tezan
• Passive hyperaemia or congestion is opposite to active hyperaemia. Congestion is usually occur due to the
dilatation of the vein when the venous blood is accumulated, the affected area usually looks bluish in color due
to the accumulation of the non-oxygenated blood. There are two types which are acute and chronic. And
beside this is local and systemic. These two things are different, acute venous congestion is possible to be
seen which happens suddenly and remain for very short period of time. Chronic congestion is possible to occur
during a long period and remain for many months or years. Venous congestion possible to occur as local and
systemic and this usually occur due to the accumulation of the an or non-oxygenated venous blood.
pulmonary Occurs
• Local venous congestion is one the outflow due to the obstruction in the vein in some organ like the total
venous obstruction in the liver.
• Systemic venous congestion: this is possible to be occur due to the left side or right side, by the way left side
Localized
heart failure will increase the rate of the pulmonary congestion while right side failure in the heart will increase
the rate of the systemic congestion. Because right side is responsible to take the blood from the an or non-
oxygenated blood from the whole body while the left will take the blood from the lung. So, when the left side of
the heart is affected and is not able to perform its normal activity, it will probably affect the amount of the blood
which is needed to be taken from the lung and as a result too much blood is possible to be accumulated in the
lung and increases in the rate of the pulmonary congestion.
 Difference between hyperaemia and congestion
A.Hyperaemia: (active hyperaemia)
• The dilation of artery so blood flow increases, causes redness in area
• Blushing
• Inflammation
• Menopausal flush (like
hyperthyroidism due to
hormonal imbalance)
• Exercise
• Fever
• Goitre
• Arteriovenous malformations

B.Congestion:- (passive hyperaemia)

• Dilatation of veins and capillaries due to impaired venous drainage.
• Too much deoxynagaed blood is accumulated.
- Here this figure will summarize what is going on during the right or left side heart failure. Right side failure will probably
make the systemic venous congestion because the blood from the these organs which are present here are taken or are
collected in the right side. And the left side is due to the left side blood will take from the lung, in case of the left side
heart failure too much blood is accumulate in the lung and increase the rate of the pulmonary congestion.
 Morphology of CVC of organs
CVC lung
Chronic venous congestion of the lung occurs in left heart failure, especially in rheumatic mitral stenosis
so that there is consequent rise in pulmonary venous pressure. Grossly, the lungs are heavy and firm in
consistency. The sectioned surface is dark The sectioned surface is rusty brown in colour referred to as
brown induration of the lungs. Histologically, the alveolar septa are widened due to the presence of
interstitial oedema as well as due to dilated and congested capillaries. The septa are mildly thickened due
to slight increase in fibrous connective tissue. Rupture of dilated and congested capillaries may result in
minute intra-alveolar haemorrhages. The breakdown of erythrocytes liberates haemosiderin pigment
which is taken up by alveolar macrophages, so called heart failure cells, seen in the alveolar lumina. The
brown induration observed on the cut surface of the lungs is due to the pigmentation and fibrosis.

CVC in lungs:-
• Venous congestion possible to be occur in the lungs. If we just have a look at this image we will see pulmonary or congestion in
the lung which is possible to be seen or occur at the result of the right side heart failure is will make some changes, one of the
change is possible to be seen increase in the alveolar septa thickness due to the accumulation too much fluid, and haemorrhage
is possible to occur too much blood is accumulated lung and as a result capillary damage blood vessel damage possible to be
seen and the RBC are moving into the space of alveoli and these RBC are destructed by the macrophage as a result different
pigment of hemosiderin possible to be seen
CVC Liver
Chronic venous congestion of the liver occurs in right heart failure and sometimes due to occlusion of inferior
vena cava and hepatic vein.
Grossly, the liver is enlarged and tender and the capsule is tense. Cut surface shows characteristic nutmeg*
appearance due to red and yellow mottled appearance, corresponding to congested centre of lobules and fatty
peripheral zone respectively.
 • CVC in liver is possible to be occur due to the obstruction of the inferior vena cava or hepatic vein. As you know the hepatic
cell will take the blood through the hepatic artery and also through the portal vein. Portal vein is responsible to transport the
blood from the for example from the intestine, pancreas, spleen, liver and this blood contain some amount of oxygen and also
contain the nutrient, and beside this some of the hepatic cell will may be blood through the hepatic artery. In general, in case
of the chronic venous congestion in the liver, generally those cells which are located in the centrilobular zone are more
affected than those cells which are located peripheral zone
• In case chronic venous congestion in liver cells which are located in the centrilobular zone are more affected than those cells
which are located in the peripheral zone, why?)

Note://
** The cells around the central lobule undergo severe hyperoxia why?
They are closer to the source of nutrients, which is the hepatic portal vein and receives oxygen from the hepatic portal vein so any
obstruction causes the cells in the center hence closer to the portal vein to undergo severe hyperoxia but peripherally located cells
receives mostly their nutrient and oxygen from hepatic artery.

Note
The difference of circulatory system and other organ is that:
• Liver receives O2 from hepatic artery and portal vein
• Liver has 2 systemic capillary(capillary→vein→capillary)
Microscopically, the changes of congestion are more marked in the centrilobular zone due to severe
hypoxia than in the peripheral zone. The central veins as well as the adjacent sinusoids are distended
and filled with blood. The centrilobular hepatocytes undergo degenerative changes, and eventually
centrilobular haemorrhagic necrosis may be seen.
Long-standing cases may show
fine centrilobular fibrosis and
regeneration of hepatocytes,
resulting in cardiac cirrhosis. The
peripheral zone of the lobule is
less severely affected by chronic
hypoxia and shows some fatty
change in the hepatocyte.
2. Haemorrhage
Haemorrhage is the escape of blood from a blood vessel. The bleeding may occur externally,
or internally into the serous cavities (e.g. haemothorax, haemoperitoneum, haemopericardium),
or into a hollow viscus. Extravasation of blood into the tissues with resultant swelling is known
as haematoma. Large extravasations of blood into the skin and mucous membranes are called
ecchymoses. Purpuras are small areas of haemorrhages (upto 1 cm) into the skin and mucous
membrane, whereas petechiae are minute pinhead-sized haemorrhages.
Microscopic escape of erythrocytes into loose tissues may occur following marked
congestion and is known as diapedesis.
Etiology. The blood loss may be large and sudden (acute), or small repeated bleeds may
occur over a period of time (chronic).
 The various causes of haemorrhage are as under:
1. Trauma to the vessel wall e.g. penetrating wound in the heart or great vessels, during
labour etc.
2. Spontaneous haemorrhage e.g. rupture of an aneurysm, septicaemia, bleeding diathesis
(such as purpura), acute leukaemias, pernicious anaemia, scurvy.
3. Inflammatory lesions of the vessel wall e.g. bleeding from chronic peptic ulcer, typhoid
ulcers, blood vessels traversing a tuberculous cavity in the lung, syphilitic involvement of the
aorta, polyarteritis nodosa.
4. Neoplastic invasion e.g. haemorrhage following vascular invasion in carcinoma of the
tongue.
5. Vascular diseases e.g. atherosclerosis.
6. Elevated pressure within the vessels e.g. cerebral and retinal haemorrhage in systemic
hypertension, severe haemorrhage from varicose veins due to high pressure in the veins of legs
or oesophagus.
• Another type of the disturbance is the haemorrhage. Haemorrhage is the escape of the blood from the blood vessel into the
outside of the body or into the interstitial space.
• It is possible to be seen under the skin. 3 types of the haemorrhage are present ecchymoses, purpuras, and petechiae.
• Petechiae haemorrhage is the pinhead-sized haemorrhage, very small. And those which are smaller than 1cm they are called
purpuras.
• Ecchymoses is another types of haemorrhage which is usually larger than 1cm, and many other clinical terms are used, for
example haematoma, when the blood is escaped from the blood vessels into the interstitial spaces is called the haematoma.
• We have two types of haemorrhage acute and chronic. Different factors have a role in the rate of the haemorrhage like a
(Trauma), (spontaneous haemorrhage in case of the aneurysm when the blood vessels is dilated in some part of the body in
case of the leukemia, pernicious anaemia, scurvy).( Inflammatory lesion) (Neoplastic invasion when the cancer cells is
produced, tumor is produced, it will make a pressure of the blood vessels and it make the increase the rate of the rupture).
• Vascular disease e.g. atherosclerosis when too much fat is accumulate or deposited it in the wall of the blood vessels this is
another factor which increase the risk of the blood vessel damage.
• Elevated pressure e.g. cerebral and retinal haemorrhage in systemic hypertension, retinal haemorrhage, cerebral
haemorrhage is possible to seen due to the pressures which is produce in the wall of artery and at the end it will
increase the rate of the blood vessel damage.
Effects. The effects of blood loss depend upon 3 main factors:
▪ the amount of blood loss;
▪ the speed of blood loss; and
▪ the site of haemorrhage.
The loss up to 20% of blood volume suddenly or slowly generally has little clinical effects
because of compensatory mechanisms. A sudden loss of 33% of blood volume may cause
death, while loss of up to 50% of blood volume over a period of 24 hours may not be
necessarily fatal. However, chronic blood loss generally produces iron deficiency anaemia,
whereas acute haemorrhage may lead to serious immediate consequences such as
hypovolaemic shock.
causes
Trauma to the blood vessel wall:
2. Spontaneous haemorrhage/ rupture of an aneurysm,
3. Inflammatory lesions of the vessel wall
4. Neoplastic invasion/ haemorrhage following vascular invasion in carcinoma of the tongue.
5. Vascular diseases/ atherosclerosis.
6. Elevated pressure within the vessels/ hypertension
Effects
• Effect of the blood loss depend of the 3 factors, these three factors will probably detect the effect of the haemorrhage, how?
Loss of the 20% of blood volume suddenly or slowly doesn’t make a big problem but if you loss 33% of the blood suddenly it
is very fatal, if you for example loss 33% , one third of the total blood volume within few minutes then you are in the risk of
death but if you loss 50% of blood within 24h this will probably doesn’t make or it is not fatal, it is fatal if you loss 33% of
blood suddenly within the very short period of time while those of 50% of blood within or after in a period which is the more
than 24h is not fatal, why??
• Because in case of losing blood suddenly within the very short period of time body does not be able to compensate the
blood which loss or which escaping the blood vessels while during or losing of the blood over a period of more than 24h
body will be able to compensate the amount of the blood which was escaped the cardiovascular system by increasing the
amount of the plasma will try to compensate the normal volume of the blood which is need to present in the body.
Shock (Too much loss of blood from blood vessels)
Shock is a life-threatening clinical syndrome of cardiovascular collapse characterized by: an acute
reduction of effective circulating blood volume (hypotension); and an inadequate perfusion of cells
and tissues (hypoperfusion). If uncompensated, these mechanisms may lead to impaired cellular
metabolism and death. Thus, by definition “true (or secondary) shock” is a circulatory imbalance
between oxygen supply and oxygen requirements at the cellular level, and is also called as
circulatory shock.
The term “initial (or primary) shock” is used for transient and usually a benign vasovagal attack
resulting from sudden reduction of venous return to the heart caused by neurogenic vasodilatation
and consequent peripheral pooling of blood e.g. immediately following trauma, severe pain or
emotional overreaction such as due to fear, sorrow or surprise.
 Clinically, patients of primary shock suffer from the attack lasting for a few seconds or minutes and develop
brief unconsciousness, weakness, sinking sensation, pale and clammy limbs, weak and rapid pulse, and low
blood pressure. Another type of shock which is not due to circulatory derangement is anaphylactic shock
from type 1 immunologic reaction.
In routine clinical practice, however, true shock is the form which occurs due to haemodynamic
derangements with hypoperfusion of the cells; this is the type which is commonly referred to as ‘shock’ if
not specified.

• Shock is a collapse in the cardiovascular system when the body cells, tissue, and organs are not able to get enough amount of
oxygen. Shock is a disturbance in the normal balance in which oxygen supply and the oxygen requirement changes, any
change by any factor will probably increase the rate of the shock.
• In general, we have two types of shock, primary is a type of shock which is produce as a result of the vasovagal attack, in
vasovagal attack there is a decrease in the blood supply.
• Primary is a vasovagal attack, the blood supply is decreased for a very short period of time which is lasting for a few seconds
to very few minute. In the primary shock which is also called initial shock there is no decrease in the blood volume it is just
decrease in the blood supply, cardiac output is decreased for a very short period of time while in case of the secondary shock
(true shock) there is a decrease in volume of the shock.
• In the primary shock also called initial shock, there is no decrease in blood volume, only blood supply decreases.
Cardiac output is decreased for a short period of time while in case of true shock or secondary shock; there is a
decrease in the volume of the blood. Beside this, we have the anaphylactic shock which is usually produced by
the release of histamine, the dilatation of the blood vessels and constriction of smooth muscles in the respiratory
system. Primary shock is neurocardiogenic syncope, in which a signal is coming from the nervous system into the
heart and this will make a sudden decrease in the heart beat and decrease in the blood pressure and this only
lasts a few seconds to few minutes. This type of shock is not produced as a result of hypovolumea it only results
from a decrease in blood supply due to the decrease of heart rate and blood pressure. While in secondary or true
shock there is shock produced due to hemodynamic derangement in which the blood supply decreases as well
as blood pressure and the cardiac output.
 Classification and Etiology
Although in a given clinical case, two or more factors may be involved in causation of true shock
(secondary shock), a simple etiologic classification of shock syndrome divides it into following
3 major types and a few other variants.

1. Hypovolemic shock. This form of shock results from inadequate circulatory blood volume by
various etiologic factors that may be either from the loss of red cell mass and plasma from
hemorrhage, or from the loss of plasma volume alone (Acute hemorrhage, dehydration from
vomiting, diarrhea, burns and excessive use of diuretics)

Hypovolemic shock: in this type of shock, the total volume of the blood is decreased and this usually occurs due to
hemorrhage, dehydration, vomiting, diarrhea and burns. And this decrease in the blood volume affects the normal
balance between oxygen supply and oxygen requirement.
 2. Cardiogenic shock. Acute circulatory failure with sudden fall in cardiac output from acute diseases of the
heart without actual reduction of blood volume (normovolaemia) results in cardiogenic shock.
• Deficient emptying e.g. (Myocardial infarction, cardiomyopathies, rupture of the heart, ventricle or
papillary muscle, cardiac arrhythmias
• Deficient filling e.g.(Cardiac tamponade from haemopericardium)
• Obstruction to the outflow e.g. (Pulmonary embolism, tension pneumothorax and dissecting aortic
aneurysm)

• In this type of shock, the total volume of blood stays normal but the cardiac output decreases. Enough amount
of blood is not pumped by the heart and this is possible to be seen in deficient emptying or deficient filling.
Deficient filling or emptying might be seen in myocardial infraction, cardiomyopathy, and rupture of the heart,
ventricle or papillary cardiac arrhythmia.
• In deficient emptying, during the contraction or relaxation (systolic and diastolic). In case of systolic, the cardiac
muscle is not able to contract properly in order to push the whole blood in the left ventricle.
• In case of deficient filling, the cardiac muscles are not able to relax normally (the diastolic phase) and this
improper relaxation, doesn’t allow the right or left atrium to take enough amount of blood from the lungs.
• Thus, when the heart does not contract or relax properly during the systolic and diastolic phase, it will affect the
amount of blood which is supposed to be sent by the heart to the rest of the body.
 2. Septic (Toxaemic) shock. Severe bacterial infections or septicaemia induce septic shock. It may
be the result of Gram negative septicaemia (endotoxic shock) which is more common, or Gram
positive septicaemia (exotoxic shock).

Septic shock is another type of shock which is produced when an infection is present for example and there is too
much inflammatory molecules which also cause the damage of the blood vessels and increase the rate of blood clot
formation and this affects the blood flow and results in this type of shock called septic shock.

4. Other types. These include following types:

i. Traumatic shock. Shock resulting from trauma is initially due to hypovolaemia, but even after
haemorrhage has been controlled, these patients continue to suffer loss of plasma volume into the
interstitium of injured tissue and hence is considered separately in some descriptions (Severe
injuries, surgery with marked blood loss and obstetrical trauma)
ii. Neurogenic shock. Neurogenic shock results from causes of interruption of sympathetic vasomotor
supply (Neurogenic shock, high cervical spinal cord injury, accidental high spinal anaesthesia and
severe head injury)
 iii. Hypoadrenal shock. Hypoadrenal shock occurs from unknown adrenal insufficiency in which the
patient fails to respond normally to the stress of trauma, surgery or illness. Administration of high
doses of glucocorticoids and secondary adrenal insufficiency (e.g. in tuberculosis, metastatic
disease, bilateral adrenal haemorrhage, idiopathic adrenal atrophy)
Neurogenic shock: a type of shock produced due to the injury of the spinal cord or the brain which affects the
sympathetic vasomotor supply so it will affect the normal blood supply.
Hypoadrenal shock: a type of shock produced due to the decrease of blood pressure. The adrenal gland is not able
to work properly and it will probably increase the risk of the adrenal shock.
QUESTION/ usually glucocorticoid is used to regulate the blood pressure so in case of the hypo adrenal shock,
glucocorticoid is given in order to increase the blood pressure and also to treat the condition, while the administration
of too much glucocorticoid will increase the rate of hypo adrenal shock why?
A high dose of glucocorticoid affect the pituitary gland, hypothalamus, and the adrenal gland and decreases the rate
of ACTH from the anterior pituitary gland and that affect the adrenal gland to release low cortisol, and lower cortisol
causes low blood pressure and shock in some cases
Pathogenesis
In general, all forms of shock involve following 3 derangements:
• Reduced effective circulating blood volume.
• Reduced supply of oxygen to the cells and tissues with resultant anoxia. • Inflammatory
mediators and toxins released from shock induced cellular injury. These derangements initially
set in compensatory mechanisms but eventually a vicious cycle of cell injury and severe
cellular dysfunction lead to breakdown of organ function.

1. Reduced effective circulating blood volume. It may result by either of the following
mechanisms:
a. by actual loss of blood volume as occurs in hypovolaemic shock; or b. by decreased
cardiac output without actual loss of blood (normovolaemia) as occurs in cardiogenic
shock and septic shock.
2. Impaired tissue oxygenation. Following reduction in the effective circulating blood volume
from either of the above two mechanisms and from any of the etiologic agents, there is
decreased venous return to the heart resulting in decreased cardiac output. This consequently
causes reduced supply of oxygen to the organs and tissues and hence tissue anoxia, which
sets in cellular injury.
3. Release of inflammatory mediators. In response to cellular injury, innate immunity of the
body gets activated as a body defense mechanism and release inflammatory mediators but
eventually these agents themselves become the cause of cell injury. Endotoxins in bacterial
wall in septic shock stimulate massive release of pro-inflammatory mediators (cytokines)
but a similar process of release of these agents takes place in late stages of shock from other
causes. Several pro-inflammatory inflammatory mediators are released from monocytes-
macrophages, other leucocytes and other body cells, the most important being the tumour
necrosis factor- (TNF)-α and interleukin-1 (IL-1) cytokines.
 • In all types of shock, blood supply is decreased. And this decrease in blood supply might be due to heart failure,
loss of blood volume in case of hemorrhage, obstruction of the blood vessels.
• when the oxygen is not reaching the cells, the cells try to compensate the condition by depending mainly on
glycolysis in order to produce too much amount of the glucose and increase the rate of the lactic acid formation
and this will increase the rate of cell damage. Beside this, when the oxygen is decreased, it will probably increase
the rate of cell injury.
• And when this cell injury appears for example due to the accumulation of too much lactic acid, the injurious cell
will secrete different chemical compounds and this will activate the activation of inflammation process, and
Leads to more cell damage.
Why does high doses of glucocorticoids cause shock?
• Because high dose of glucpcorticoid affect the pituitary gland, hypothalamus, and adrenal gland.
• Low ACTH→adrenal gland→low cortisol→low pressure→shock
 Pathophysiology (Stages of Shock)
Although deterioration of the circulation in shock is a progressive and continuous phenomenon and
compensatory mechanisms become progressively less effective, historically shock has been divided
arbitrarily into 3 stages:
1. Compensated (non-progressive, initial, reversible) shock.
2. Progressive decompensated shock.
3. Irreversible decompensated shock.
Compensated (non-progressive, initial, reversible) shock. In the early stage of shock, an attempt
is made to maintain adequate cerebral and coronary blood supply by redistribution of blood so that
the vital organs (brain and heart) are adequately perfused and oxygenated. This is achieved by
activation of various neurohormonal mechanisms causing widespread vasoconstriction and by
fluid conservation by the kidney. If the condition that caused the shock is adequately treated, the
compensatory mechanism may be able to bring about recovery and reestablish the normal
circulation; this is called compensated or reversible shock.
Progressive decompensated shock. This is a stage when the patient suffers from some other stress or
risk factors (e.g. pre-existing cardiovascular and lung disease) besides persistence of the shock so that
there is progressive deterioration. The effects of progressive decompensated shock due to tissue
hypoperfusion are as under:
i. Pulmonary hypoperfusion. Decompensated shock worsens pulmonary perfusion and increases
vascular permeability resulting in tachypnoea and adult respiratory distress syndrome (ARDS). ii.
Tissue ischaemia. Impaired tissue perfusion causes switch from aerobic to anaerobic glycolysis
resulting in metabolic lactic acidosis. Lactic acidosis lowers the tissue pH which in turn makes the
vasomotor response ineffective. This results in vasodilatation and peripheral pooling of blood.
Clinically at this stage the patient develops confusion and worsening of renal function.
Irreversible decompensated shock. When the shock is so severe that in spite of compensatory
mechanisms and despite therapy and control of etiologic agent which caused the shock, no
recovery takes place, it is called decompensated or irreversible shock.
During shock, 2 mechanisms are activated directly. When the blood supply is decreased in which they try to control
the condition and regulate the blood flow.
1) Widespread vasoconstriction: this is really important to regulate the blood supply especially in coronary and
carotid arteries.
2) Fluid conservation: the kidneys will try to decrease the amount of water and sodium excretion. Retention of
sodium and water is important to increase the blood pressure.
If these mechanisms succeed then the shock will be controlled and the normal homeostasis returns back and the
effects of the shock will dramatically decrease.
And during this stage of shock, the shock is called the decompensated shock which means it is a reversible shock.
Irreversible decompensated shock is the last stage of shock.
In this stage, the patient most probably won’t survive, because a very big damage occurs and the normal
mechanisms responsible to control the condition are not able to compensate the condition.
Clinical Features and Complications
The classical features of decompensated shock are characterised by depression of 4 vital
processes:
• Very low blood pressure
• Subnormal temperature
• Feeble and irregular pulse
• Shallow and sighing respiration
• In addition, the patients in shock have pale face, sunken eyes, weakness, cold and
clammy skin.
 ▪ Life-threatening complications in shock are due to hypoxic cell injury resulting in immuno inflammatory
responses and activation of various cascades (clotting, complement, kinin). These include the following*:
• Acute respiratory distress syndrome (ARDS)
• Disseminated intravascular coagulation (DIC)
• Acute renal failure (ARF)
• Multiple organ dysfunction syndrome (MODS)
• With progression of the condition, the patient may develop stupor, coma and death.

Complications of shock include

• Low BP
• Irregular pulse
• Shallow respiration
• Subnormal temperature

Life threatening conditions include:

• DIC
• ARF-> acute renal failure
• MODS-> multiple organ
• dysfunction syndrome