ppt contains concept of cell injury and cellular adaptation and mechanism of inflammation and wound healing.

1. Cell Injury and
Inflammation
BY MS. ANKITA BURANDE
ASSISTANT PROFESSOR
NAGPUR COLLEGE OF PHARMACY

2. There are two separate field involve in pathophysiology
First is Physiology: the study of body and its function
Second is Pathology: the study of disease and its impact on body.
When combine, pathophysiology concern with study of mechanism
responsible for initiation, development, treatment of pathological
process in humans and animals and provide appropriate care to the
patient.
Pathophysiology

3. Basic principals of Cell Injury & Adaptation
Introduction, Definitions,
Homeostasis,
Components and Types of Feedback systems,
Causes of cellular injury,
Pathogenesis (Cell membrane damage, Mitochondrial damage, Ribosome damage, Nuclear
damage)
Morphology of cell injury – Adaptive changes (Atrophy, Hypertrophy, hyperplasia, Metaplasia,
Dysplasia),Cell swelling,
Intra cellular accumulation, Calcification, Enzyme leakage and Cell Death Acidosis & Alkalosis,
Electrolyte imbalance.

4. Introduction
Cells are the basic units of tissues, which form organs and systems in the human body.
Traditionally, body cells are divided into two main types: epithelial and mesenchymal cells
 In 1859, Virchow first published a cellular theory of disease, bringing in the concept that
diseases occur due to peculiarities at the level of cells
Thus, most forms diseases begin with cell injury followed by consequent loss of cellular
function.
Cell injury is defined as a variety of stresses a cell encounters as a result of changes in internal
and external environment.
In general, cells of the body have the inbuilt mechanism to deal with changes in the
environment to an extent.
The environment of a living cells frequently changing. Thus, the availability of nutrient en,
blood supply and regulatory substances like hormones is not the same at all time. Homeostatic
mechanisms try to keep these changes within physiological range.

5. The cellular response to stress
The cellular response to stress may vary and depends upon the
following variables:
i) Type of cell and tissue involved
ii) Extent and type of cell injury
Various forms of cellular responses to cell injury may be as
follows:
1. When there is improved working demand, the cell may
adapt to the changes which are revealed morphologically and
then revert back to normal after stress is removed (Cellular
adaptation)
2. If the stress is mild to moderate, the injured cell may recover
(reversible cell injury) while when the damage is persistent cell
death may occur (Irreversible cell injury)

6. Homeostasis refers to stability, balance or equilibrium in the body's internal environment due to constant interaction of
body's many regulatory processes.
Maintaining a stable internal environment requires constant monitoring and adjustments as conditions change.
Components Homeostatic mechanism is maintained by control system or feedback system, having three components;
1. Receptor (sensor): It is a body structure that monitors changes in a controlled condition and sends input to a control
center (integrator). The input is in the form of nerve impulses or chemical signals. Example: Certain nerve endings in the
skin sense temperature and detect changes.
2. Control centre (integrator): It integrates (puts together) data from sensor provides commands to an effector but this
time the effector produces a physiological response that adds to the initial changes in the controlled condition. Example-
the brain, sets the range values within which a controlled condition should be maintained, evaluates the input it receives
from receptors and generates output commands when they are needed. The output from the control center occurs as
nerve impulses, or hormones and other chemical signals.
3. Effectors: It is the mechanism that has a body structure that receives output from the control center and produces a
response or effect that changes the controlled condition. Nearly every organ or tissue in the body can behave as an
effector
Homeostasis

7. Homeostasis
Example: If the temperature of a body is decreased from set point, the receptor detects the
change in temperature and signals the thermostat (effector). Result in shivering which generate
heat and raises body temperature. Similarly, it the temperature is increased from set point,
thermo receptor are involved in the detection of temperature change . Once stimulated, it act
on effectors for cooling (sweat gland) or heating (e.g. muscles) the body to reverse the change to
set point.

8. Concept of Feedback Mechanism in Homeostasis
There are types of feedback:
1. Negative feedback: The effector
response decrease or negates the effect of
the original stimulus maintaining
homeostasis.
2. Positive feedback: The effector response
increase or enhance the effect of the
original stimulus maintaining homeostasis.

10. Causes of Cell Injury:
A variety of factors may be responsible for cell injury. The important ones are described here.
(a) Hypoxia: Hypoxia (deficiency of oxygen) is the most common and most important cause of cell injury.
The most common cause of hypoxia is ischemia (inadequate blood supply) due to impaired arterial supply
of venous drainage. However, hypoxia may result from other causes as well e.g. cardiac failure, respiratory
failure, anemia, carbon monoxide poisoning, etc.
B) Physical Stress: Trauma disrupts the physical integrity of cell extreme temperatures cause denaturation
of proteins and electric shock disrupts the ionic equilibrium and trans membrane potentials. Thus, different
types of physical factors can damage the cells in different ways
(c) Drugs and Chemicals: Almost all chemicals, including the endogenous ones like hormones and even the
vital ones like glucose, are capable of inducing cell injury and death. Electrolytes may damage cells by
disturbing the ionic equilibrium across their membranes. Poisonous chemicals' may disturb the osmotic
balance between the inside and outside of the cell, alter membrane permeability or disrupt the integrity
and activity of enzymes. The best examples of chemicals, which produce cell injury, are cytotoxic drugs.
(d) Microbial Agents: Infections and infestations may damage cells many ways. Micro organisms elaborate
toxins or trigger inflammation which produces cell injury. Intra cellular pathogens (like Plasmodium)
directly produce cell injury.

11. Causes of Cell Injury:
(e) Immunologic Factors: Allergic reactions may produce devastating cell injury as in the case of
the cytolytic allergic reactions. Similarly, auto immune reactions may cause cell injury, as in
Type-I diabetes mellitus (DDM).
(f) Nutritional Derangements: A deficiency or an excess of nutrients may result in nutritional
imbalances.
Nutritional deficiency diseases may be due to overall deficiency of nutrients (e.g. starvation), of
protein calorie (e.g. marasmus, kwashiorkor), of minerals (e.g. anaemia), or of trace elements.
 Nutritional excess is a problem of affluent societies resulting in obesity atherosclerosis, heart
disease and hypertension.
g)Aging: Cellular aging leads to impaired ability of the cells to undergo replication and repair,
and ultimately lead to cell death culminating in death of the individual.
h) Psychogenic Disease, i) Iatrogenic Factors, j) Idiopathic Diseases.

12. Cellular adaptation changes
 The cell adaptations are many, some involve up or down regulations on specific cellular
receptor which involves in the metabolism of certain components.
(1) For example regulation of cell surface receptors involved in uptake and degradation of low
density lipo-proteins (LDL)
(2) the other are induction of new proteins synthesis by target cells such as heart stock or stress
shock proteins which protects cells from some form of injury.
The common adaptive responses are Atrophy (decreased cell size), hypertrophy (increased cell
Size), hyperplasia (increased cell number), metaplasia (conversion of one cell type to another),
and dysplasia (disorderly/abnormal growth growth). Each of these changes is potentially
reversible when the cellular stress is relieved.

13. ATROPHY
 Atrophy is a decrease or becoming smaller in cell size, loss of cell substance is named atrophy. If
atrophy takes place in an enough number of an organ's cells, the complete organ gets smaller or
become atrophic. Atrophy can affect any organ, but it is most commonly found in the hen
skeletal muscle, the brain, and as physiologic or pathologic.
 Physiologic atrophy takes place with early development. For example, the thymus gland
undergoes physiologic atrophy during childhood. Pathologic atrophy takes place as an outcome
of decrease in blood supply, nutrition, hormonal stimulation, workload and pressure.
 Atrophy getting old ages the brain cells to become atrophic and endocrine-dependent organs,
such as the gonads, to get smaller as hormonal stimulation decreases.

14. HYPERTROPHY
 Hypertrophy is an increase in the size of cells. which leads to increase in organ. Hypertrophy is due to
increased functional demand or by specific hormonal stimulation, which may occur under
physiological or pathological conditions.
 For example in the physiological growth of uterus during pregnancy, which involves both
hypertrophy and hyperplasia. The cellular hypertrophy is stimulated by estrogen receptor, which
allows its interaction with nucleus DNA resulting in increased synthesis of smooth muscle proteins
and increase in cell size of the uterus. Thus this physiological hypertrophy is due to hormonal
stimulations.
 Hypertrophy is an adaption response which is also due to enlargement of muscles. The cells of the
heart and kidneys are particularly responsive to enlarge. The striated muscle cells of both the heart
and skeletal muscles are capable of hypertrophy. Physiologic hypertrophy in skeletal muscle occurs in
response to heavy work.
 The hypertrophy may reach to a limit beyond which enlargement by muscle mass is no longer
compensated for increased burden and results in cardiac failure.

15. HYPERPLASIA
 Hyperplasia is an increase in the number of cells resulting from an increased rate of cellular
division.
The cell growth is increased due to multistep process involving the production of growth factors,
which stimulate the remaining cells to synthesize new cell components and, ultimately, to
divide.
 Hyperplasia and hypertrophy are closely related and often develop simultaneously in tissue.
Both hyperplasia and hypertrophy take place if the cells are capable of synthesizing DNA.
 Cardiac and skeletal muscle cells have no capacity for hyperplastic growth and thus usually
undergo only hypertrophy.

16. HYPERPLASIA
Hyperplasia can be physiologic or pathological: Physiology hyperplasia is divided into
(1) Hormonal hyperplasia: most from of pathological hyperplasia is due to excessive hormonal
stimulation and its effect on growth factor on targeted cells. It is seen in proliferation of the
epithelium of the female breast at puberty and during pregnancy
(2) Compensatory hyperplasia: is an adaptive mechanism that enables certain organs to
regenerate. For example when a portion of tissue is removed, mitotic activity in the remaining
liver cells begins as early 12 hours after hypertrophy resulting the liver to attain its normal
weight.
 The various specific factors that appear to be involved in liver regenerating are transforming
growth factor hepatocyte growth factor (HGE».is a mediator in vitro of liver regeneration. In
addition, other in vitro growth factors and cytokines (cell-signaling proteins) that increase
hepatic cell growth regeneration includes transforming factor-alpha (TGF-a), epidermal growth
factor (EGF), necrosis factor-alpha (TNF-).

17. METAPLASIA
 Metaplasia is the reversible replacement of one adult cell by another. sometimes less
differentiated, cell type.
 Metaplasia is best seen in the form of squamous change that occurs in respiratory tract in the
habitual cigarette smoke. The normal columnar ciliated epithelial cells of trachea and bronchi
are replaced mainly by striated squamous epithelial cells.

18. DYSPLASIA
 Dysplasia is related to occurs when abnormal changes in the size, shape, and organization of
adult cells which is related hyperplasia and is often called atypical hyperplasia.
 It is not consider as true adaptive process. These changes are strongly associated with common
neoplastic growth and often found adjacent to cancerous cells.

19. Pathogenesis of Cell Injury
 Cell injury is cause by various reasons. Mechanism and location of cell injury is well defined
based on injurious agent or injury causing agent.
 Cell Injury Is of two type: Reversible Cell Injury and Irreversible cell injury
 Pathogenesis of cell injury involve below two pathways
1. Ischemic or Hypoxic Injury
2. Free radical mediated cell injury.

20. ISCHEMIC AND HYPOXIC INJURY
1. Cellular Injury: The term, ischemia, has been used to denote deficient blood supply to due to
obstruction of the arterial inflow. The disorders characterized by ischemia such as myocardial infarction,
stroke, and peripheral vascular disease, most frequent causes of cell Injury or cell damage.
2. Cell damage: The effect of hypoxia is in the aerobic respiration cells involving the oxidative
phosphorylation reaction in mitochondria. The generation of adenosine triphosphate membrane (ATP)
slows down or stops which may effect on many oxidation systems which causes failure of the active sodium
pump, this effects the accumulation of sodium intracellular and potassium out from fusion of the cell.
Thus, it produces acute cellular swelling due to water. This stage is reversible if oxygen is restored.
If ischemia persists, the irreversible injury may be the result. It is associated with vacuolization of the
mitochondria which includes extensive damage plasma membrane, swelling of lysosome, and particularly
massive calcium influx into cell, leads to Ca++ deposits in mitochondrial matrix and efflux the cellular
enzyme creatine kinases (CK) and lactate dehydrogenase; There is continued loss of proteins, essential
coenzyme and ribonucleic acid from the hypermeable membranes. The cell reaches at stage to necrosis or
cell death. This sage is called Irreversible Injury.

21. ISCHEMIC AND HYPOXIC INJURY
3. Nuclear damage: The decrease in cellular ATP and Increase in adenosine monophosphate
(AMP) also stimulates the enzyme Phospho-fructotokinase glycolysis in order to maintain the
cells energy source by generating the ATP from glycogen. The glycogen gets rapidly depleted.
Glycolysis results in the accumulation of the lactic acid and inorganic phosphate from the
hydrolysis of phosphate ester, it reduces the intercellular pH and glycogen which results in
clumping the chromatin. This stage is reversible is restore if oxygen d.
 If ischemia persists, the cell reaches at the next stage- irreversible injury. The fall of pH leads
to injury to the liposomal membranes followed by leakage of their enzymes in to cytoplasm,
activation of acid hydrolases and enzymatic digestion of cytoplasmic and nuclear components.

22. 4. Ribosome damage:
 This process also involves oxidative phosphorylation, decrease the ATP the result detachment of
ribosomes from the granular endoplasmic reticulum and dissociation polysomes into
monosomes, decreased proteins synthesis , lipids deposition and lipotoxicity.
This stage cell may recover the injury and is called reversible injury If hypoxia continues, it will
lead to increased membrane permeability and diminished mitochondrial functions. In
mitochondria will appear normal, slightly swollen or condensed, the endoplasmic reticulum
dilated and entire cell is markedly swollen, a stage arises called apoptosis irreversible injury.
5. Mitochondrial Damage:
Cell injury or damage occurs as a result of the initial ischemia. ATP levels and intracellular pH
decreases as a result of anaerobic metabolism and lactate accumulation. As a consequence,
ATPase-dependent ion transport mechanisms become dysfunctional, this stage is called
reversible Injury if hypoxia is restored. If hypoxia continue which leads to contributing an
increased intracellular and mitochondrial calcium levels (calcium overload), cell keeps swelling
and rupture, and thus, there is cell death by necrotic, necro-apoptotic, and autophagic
mechanisms

23. Free Radical Mediated cell injury
Chemical species with unpaired or odd number of electron are called as free radicals.
 In Biological system the term free radicals mostly refers to reactive oxygen species (ROS). The
major ROS are superoxide anion (O2), hydrogen peroxide (H2O2), hydroxyl radical (OH), Beside
ROS, reactive nitrogen species (RNS) includes nitric oxide (NO), Peroxynitrite (NO3), S-
nitrosothile also contribute to generation of free radicals.
 These radicals are extremely unstable and react with inorganic membrane and nucleic acid in
the cell and start the chain of damage.
 These radicals are emitted within the cell due to absorption of radiant energy e.g. U V light,
X-rays or reduction reactions that occurs during normal metabolic reactions or may be derived
from enzymatic metabolism of exogeneous chemicals.

24. Free Radical Mediated cell injury
1. Radiation injury: Radiation enters a cell; it can be absorbed by macromolecules directly, but
more commonly it reacts with water to produce free radicals such as OH, H.
 These radicals interact with membranes nucleic acid and key elements within cell.
macromolecules such as proteins and DNA.
 The enzymatic and structural proteins depend on their three-dimensional (3-D) structure for
their function, and this 3-D structure is dependent upon various types of chemical bonds. These
bonds are disrupted by radiation, mostly by the intermediation of free radicals, and the proteins
are then incapable of performing their structural or enzymatic duties and resulting in the
induction of mutation or cell death.
2. Oxygen Toxicity: When excessive quantities of oxygen is administered in patients resulting
symptoms bodily disturbance are from breathing due to high partial pressures of oxygen.
 Symptoms observed such as visual and hearing abnormalities, unusual fatigue twitching,
anxiety, confusion, in-coordination, and convulsions. The formation of free while breathing,
muscular Oxygen radical causes inhalation the pulmonary therapy.

25. Free Radical Mediated cell injury
3) Chemical Injury: They can by combining with some molecular component or cellular
organelle. For example in case of mercuric chloride poisoning mercury bind to sulfhydryl
groups of the cell membrane and other proteins, causing increase permeability and inhibition
of ATPase dependent transport. Many anti-neoplastic chemotherapeutic agents agents and
antibiotic drugs also induced cell damage by direct cytotoxic effects in the induction of
mutation or cell death.

27. Morphological changes in reversible cell
injury: Cellular swelling
 Cellular swelling applicable to accumulation of water, or hydropic swelling, is the manifestation
of most forms of reversible cell injury.
 Hydropic swelling results from abnormal function of the sodium-potassium (Na'-K') pumps that
normally maintain ionic equilibrium f pump the cell. In this stage cell membrane is swell and the
channels become closed, the Nat-K+ unable to exchange the ions results in accumulation of
sodium ions within the cell, creating osmotic gradient for water entry.
 Because Na"-K´ pump function is dependent on the presence of cellular ATP, any injury that
results in insufficient energy production also will result in hydronic swelling.
Hydropic swelling is characterized by a large, pale cytoplasm, dilated endoplasmic reticulum,
and swollen mitochondria.
With severe hydropic swelling, the endoplasmic reticulum may rupture and form large water-
filled vacuoles. Generalized swelling in the cells of a particular organ will increase in size and
weight of organ. The swelling of cell is reversible.

28. Cellular swelling
The morphological changes resulting from reversible injury, are of two types: cellular swelling and
fatty changes.
Cellular swelling applicable to accumulation of water, or hydropic swelling, is the manifestation of
most forms of reversible cell injury.
 Hydropic swelling results from abnormal function of the sodium-potassium (Na'-K') pumps that
normally maintain ionic equilibrium f pump the cell. In this stage cell membrane is swell and the
channels become closed, the Nat-K+ unable to exchange the ions results in accumulation of sodium
ions within the cell, creating osmotic gradient for water entry.
 Because Na"-K´ pump function is dependent on the presence of cellular ATP, any injury that results in
insufficient energy production also will result in hydronic swelling.
Hydropic swelling is characterized by a large, pale cytoplasm, dilated endoplasmic reticulum, and
swollen mitochondria.
With severe hydropic swelling, the endoplasmic reticulum may rupture and form large water-filled
vacuoles. Generalized swelling in the cells of a particular organ will increase in size and weight of
organ. The swelling of cell is reversible.

29. Cellular swelling
The ultra structural changes of reversible cell injury
include:
 (1). Plasma membrane alteration, blabbing, blunting,
distortion of microvilli.
 (2). Loosening of intercellular attachments
3) Creation of myelin
(4). Mitochondrial changes, mitochondrial swelling
 (5) Deletion of endoplasmic reticulum,
It these changes occurs in cell indicate that cell
undergoes swelling.

30. Morphological changes in irreversible cell
injury: Apoptosis
The morphological changes resulting from reversible injury, are of two types: Necrosis and Apoptosis.
1. Apoptosis: Apoptosis (from the Greek for "a falling off") is a highly programmed cell death or cellular
suicide.
 The different stages of apoptotic cell death start by cellular shrinkage and chromatin condensation,
concomitant with formation of membrane blebs.
 Organelles and nuclei fragment and the blebs begin formation of apoptotic bodies which are eventually
engulfed macrophages or neighboring cells by endocytosis/phagocytosis.
 The lack of release of cellular components to the extracellular fluid results in the absence of inflammation.
Apoptosis is responsible for number of physiological events including the destruction of cell during
embryogenesis for hormone-dependent involution as occur in death immune cells after cytokine
depletion.
 The apoptosis may be triggered by pathologic stimuli such as radiation and virus. The best example is the
apoptotic cell fragments are found in liver cells due to viral hepatitis.

31. 

32. Necrosis
 Necrosis is the death of body tissue. It occurs when too little blood flows to the tissue. This can
be from injury, radiation, or chemicals. Necrosis cannot be reversed. When large areas of tissue
die due to a lack of blood supply, the condition is called gangrene.
Depending on appearance and changes in the mass of necrotic cells, necrosis can be of different
type including coagulative necrosis (most common), liquefactive necrosis, caseous necrosis and
fatty necrosis. Necrosis is the result of two concurrent processes, enzymatic digestion of cell and
denaturation of proteins.

33. Necrosis
Types of Necrosis:
1. Coagulative Necrosis: Hypoxic death of cells in all tissues except brain is characterized by
coagulative necrosis. The injury or the resulting acidosis causes denaturation of proteins.
Myocardial infarction leads to coagulative necrosis.
2. Liquefactive Necrosis: Cell injury by localized bacterial and sometimes fungal infections leads
to liquefactive necrosis. The nucleus of infection attracts large number of leukocytes. The dead
cells are completely digested to liquefaction.
3. Caseous Necrosis: The cheesy-white appearance of the necrotic area imparts the name
'caseous' to this type of necrosis. It is seen in the foci of tubercular infection.
4. Fat Necrosis: It is not a specific pattern of necrosis. Instead, the term denotes focal areas of
fat destruction. It is pathognomic of acute pancreatitis or other pancreatic injury in which
activated pancreatic enzymes are released into adjacent parenchyma of peritoneal cavity. These
enzymes liquefy cell membranes in adipose tissue. The free fatty acids thus generate soaps
producing chalky-white areas.

34. Gangrene:
 When large areas of tissue die due to a lack of blood supply, the condition is called gangrene.
3 types of gangrene
1. Dry Gangrene: Usually occur in limb, originates from finger or toes, affected due to less blood
supply, spread from origin upward till it reaches to point of blood supply.
2. Wet Gangrene: occur in wet tissues and organ like mouth, bowel, lungs and cervix. Occur due
blockage of vein rather arteries.
3. Gas Gangrene: Special form of wet gangrene, formed by gas forming Clostridia + bacteria and
gain entry into open wound, produce toxins that causes necrosis and edema

35. Differentiation between Necrosis and Apoptosis:

36. Intracellular Accumulation
 In some circumstances cells may accumulate abnormal amounts of various substances, which may be
harmless or associated with varying degrees of injury.
The substance may be located in the cytoplasm, within organelles (typically lysosomes), or in the
nucleus, and it may be synthesized by the affected cells or may be produced elsewhere.
There are four main pathways of abnormal intracellular accumulations:
1. Insufficient removal of a normal substance to defects in mechanisms of transport, as in fatty
change in the liver.
2. Accumulation of an abnormal endogenous substance as a result of genetic or mutated acquired
defects in its folding, packaging, transport, or secretion, as with certain forms of a1-antitrypsin.
3. Failure to degrade a metabolite due to inherited enzyme deficiencies. The resulting disorders are
called storage diseases.
4. Deposition and accumulation of an abnormal exogenous substance when the cell has neither the
enzymatic machinery to degrade the substance nor the ability to transport it to other sites.
Accumulation of carbon or silica particles is an example of this type of alteration.

37. Intracellular Accumulation
1. Fatty changes: Any abnormal accumulation of triglycerides within parenchymal cell is known as fatty changes.
Most often seen in liver. E.g. alcohol abuse and diabetes induced obesity is well known cause of fatty changes in
liver.
3. Proteins: Morphologically visible protein accumulation is less common than lipid accumulation. They may
occur when excess amount are presented to the cell or if the cell synthesize excessive amounts. E.g. in Kidney,
albumin filtered through glomerulus are normaly absorbed by pinocytosis in PCT (Proximal convoluted tubules).
However in disorder e.g. nephrotic syndrome heavy protein leakage occur in glomerular filter
4. Glycogen: excessive intracellular deposition of glycogen are associated with abnormality in metabolism of
either glucose or glycogen. In Uncontrolled diebetis mellitus, glycogen accumulates into renal epithelial, cardiac
myocytes and B cell of islets of Langerhans.
5. Pigments: these are color substances from exogenous, coming outside the body as carban or synthesised
within body such as lipofuscin and certain derivative of haemoglobin. E.g Melanin is endogenous brown black
pigment that are synthesized by melanocytes cell of epidermis cause darkning of skin.
7. Hemosiderin: haemoglobin derived granular pigment that is golden yellow to brown and accumulates in tissue
when there is a local or excess synthesis of iron.

38. Pathologic Calcification
Deposition of calcium salts in tissues other than osteoid or enamel is called pathologic or
heterotopic calcification.
Two type of pathologic calcification are
1. Dystrophic Calcification: characterised by deposition of calcium salts in degenerated tissues
with normal calcium metabolism and normal serum calcium level.
2. Metastatic Calcification: occurs in normal tissue and associated with deranged calcium
metabolism and hypercalcemia.

40. Enzyme leakage
 Release of intracellular enzyme into extracellular space is a marker of cell damage in various
disease e.g. liver, lungs, heart.
 In Normal state, the plasma membrane is impermeable to enzyme hence enzyme leakage
indicates sever changes to membrane integrity or damage.
 This enzyme leakage, occur due to energy depletion e.g. in ischemia or shock or by direct
membrane damage cause by various toxins.
 Ischemia or inhibition of enzyme metabolism results in ATP depletion leading to failure of Na, K
and Cl pump and swelling of cell membrane.
 Ca2+ leak into cell activate the enzyme Phospholipase and formation of eicosanoids, affecting
cytoskeleton and formation of oxidants.
 The results of these reaction cause damage to cell membrane. Very small part of enzyme
leakage occur in reversible phase but substantial enzyme leakage occur in irreversible damage

41. Cell Acidosis & Alkalosis
1. Acidosis: it is process of causing increased acidity in blood and other body tissue, i,e,
increase in hydrogen ions concentration.
 Acidosis occurs when kidney and liver fails to maintain the bodies pH at optimal level.
 In body many processes produce acid. Lungs and kidney can usually compensate for slight
change in pH but problem with these organ can leads to excess acid accumulation in body.
 Acidity of blood is measured by determining its pH. pH of blood is around 7.4
 According to American Association of Clinical Chemistry (AACC) acidosis is characterised by pH
of 7.35or lower. And alkalosis means pH of 7.45 or more.
 Acidosis can leads to numerous health issues or sometimes it can be life-threatening.
 Causes of Acidosis: a. Respiratory Acidosis b. Metabolic Acidosis.

42. Acidosis
A. Respiratory Acidosis: It occur when too much of CO2 builds in body. Normally lungs remove CO2 during
breathing. However, sometimes body can’t get rid of enough CO2 due to
 Chronic Airway conditions like Asthma, Injury in chest
 Obesity, sedative misuse, overuse of alcohol, muscles weakness in chest, problems in nervous system, deform
chest structure.
Symptoms: Fatigue, Become tired easily, Confusion, Shortness of breath, Sleepiness, Headache
B. Metabolic Acidosis: metabolic acidosis start in kidney instead of lungs. It occur when kidney is not able to
eliminate acid. Three major form of metabolic acidosis.
1. Diabetic acidosis occur in diabetic patient due to deficiency of insulin, ketone bodies builds up in body and
acidify the blood.
2. Hyperchloremic Acidosis: results from loss of sodium bicarbonate. This base helps to keep the blood neutral.
Both diarrhoea and vomiting's cause this type of acidosis.
3. Lactic Acidosis: occur when too much of lactic acid secreted in body. Causes can include chronic alcohol use,
heart failure, cancer, seizers, liver failure, prolong lack of oxygen and low blood sugar. Even prolong exercise
can leads to lactic acid build up.
4. Symptoms: Rapid and shallow breathing, Confusion, fatigue, lack of appetite, Jaundice, increase heart rate,
breath that smells fruity, which is a sign of diabetic acidosis.

43. Alkalosis:
Alkalosis is excessive blood alkalinity caused by over abundance of bicarbonate in blood or loss
of acid from blood (metabolic alkalosis) or low level of carbon dioxide in blood that results from
rapid or deep breathing (Respiratory alkalosis).
Four type of alkalosis
1. Respiratory: occur when amount of carbon dioxide in bloodstream decreases than normal
level. Caused by hyperventilation, high fever, lack of oxygen, salicylate poisoning, being in high
altitude, liver disease, lungs disease.
2. Metabolic: occur when body loose too much acid or gains too much base, this caused by
excessive vomiting, overused of diuretics, adrenal disease, large loss of potassium or sodium,
antacid, accidental ingestion of bicarbonate.
3. Hyperchloremic : cause due to level of chloride decreased in body this can be due to excessive
vomiting or sweating .
4. Hyperkalemic: occur due to lack of potassium in body. Kidney disease, excessive sweating,
diarrhoea are reasons for loss of potassium.

44. Symptoms
 Nausea,
 Numbness
 Prolong muscle spasm
 Muscle twitching
 Hand tremor
 Dizziness
 Difficulty breathing
 Confusion
 Shock and coma

45. Electrolyte imbalance

46. Electrolyte imbalance