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Ramp - Pathophysiology > Basic Pathophysiology > Flashcards

Basic Pathophysiology Flashcards

1
Q

Define Disease.

A

Disease is a structural or functional change in the body that is harmful to the organism.

Some changes in the body are normal, such as pregnancy, puberty or increases in muscle mass whilst athletes train, and the cells and tissues in the body can adapt to minor fluctuations in their environment, in order to maintain homeostasis.

Disease occurs when the cellular environment changes to such a degree that tissues are no longer able to perform their function optimally, for example in diabetes, extracellular tissue of blood vessel walls undergoes changes that lead to narrowing of the blood vessels, which decreases blood flow, which decreases oxygen delivery,and can eventually cause irreversible damage to tissues such as in the heart and kidneys.

When disease is occurring the ability of cells or tissues to perform their function is compromised, with deleterious consequences to the organism.

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2
Q

What is the ‘Cellular basis of disease?’

A

A philosophy developed by scientists which states that diseases can be traced to deranged structures or functions of organs, tissues or cells.

Today the definition has been expanded to include changes at the molecular level, including proteins, and ultimately, genes.

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3
Q

Define Pathology.

A

In the broadest sense pathology is the study of disease.

Pathology includes the study of basic structural and functional changes associated with a disease, as well as the sequence of events that leads from structural and functional abnormalities to clinical manifestations.

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4
Q

Define Pathophysiology.

A

The study of the sequence of events that leads from structural and functional abnormalities to clinical manifestations of disease.

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5
Q

Structural Disease.

Describe ‘structural’ disease.

A

Also known as organic diseases.

Characterised by structural changes within the body, known as lesions.

Lesions may be visually identified by the naked eye, or by microscope, and with molecular medicine may now now be recognised at the level of proteins and genes.

3 major categories of structural disease are:

  • Genetic and developmental diseases
  • Acquired injuries and inflammatory diseases
  • Hyperplasias and neoplasms
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6
Q

Structural Disease.

Describe ‘Genetic and developmental diseases’

A

Genetic diseases are Caused by abnormalities in the genetic makeup of an individual, either at:

  • the level of chromosomes, ie. increased numbers or translocations.
  • the genetic level, ie. mutations.

Developmental diseases develop during an individuals life in utero, ie. embryonic and feral development.

The range of genetic and developmental abnormalities is very broad, extending from birth deformities to biochemical changes caused by genes but influenced by environment, so appearing later in life, ie. Diabetes Mellitus.

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7
Q

Structural Disease.

Describe ‘Acquired injuries and inflammatory diseases’

A

Degenerative and inflammatory diseases are caused by forces or agents that:

  • destroy cells or intercellular substances.
  • deposit abnormal substances in cells and tissues.
  • cause the body to injure itself by by means of the inflammatory process.

External agents of injury include physical and chemical substances and microbes.

Internal mechanisms of injury are:

  • vascular insufficiency.
  • immunologic reactions.
  • metabolic disturbances.

The 2 general reactions reactions to injury are:

  • inflammation
  • repair
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8
Q

Structural Disease.

Describe inflammation

A

A vascular and cellular reaction that attempts to:

  • localise the injury
  • destroy the offending agent
  • remove damaged cells and other materials

A stereotyped response with several variations.

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9
Q

Structural Disease.

Describe repair

A

The replacement of damaged tissue by new tissue of the same type and/or fibrous connective tissue.

Greatly influenced by the type of tissue or organ that has been injured.

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10
Q

Structural Disease.

Describe ‘hyperplasias and neoplasms’

A

Hyperplastic and neoplastic diseases are those in which the basic abnormality is an increase in cell populations.

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11
Q

Structural Disease.

Define Hyperplasia

A

A proliferative(rapid growth) reaction to a prolonged external stimulus.

Usually regresses when the stimulus is removed.

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12
Q

Structural Disease.

Define Neoplasia

A

Results from genetic changes that favour the growth of a single population of cells.

Divided into 2 groups:

  • Benign
  • cells remain localised
  • Malignant
  • cells develop ability to grow into surrounding tissues or even migrate to other tissues.
  • colloquial term for malignant neoplasm is Cancerl

Certain types of hyperplasia can evolve, through a series of genetic changes induced by external agents, into malignant neoplasms.

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13
Q

Functional Disease.

Describe ‘functional disease’

A

Diseases in which there are no visible lesions, at least during the onset of the disease.

The basic change is a physiological or functional one.

The 2 most common functional disorders are:
- tension headache
- IBS
these disorders may be the result of unconscious stimulation of the autonomic nervous system.

Other examples and method of diagnosis:

  • Diabetes Mellitus - laboratory evidence of increased circulating blood glucose.
  • Hypertension - increased blood pressure readings.

Over time structural changes become evident, first in blood vessels, then in the form of organ damage, ie. necrosis of renal tissue, and it’s replacement by fibrosis, ultimately leading to stroke, heart disease, blindness and kidney disease.

Many mental illnesses, diabetes, hypertension, are considered functional disorders but there is increasing evidence that they may have an organic/genetic basis.

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14
Q

Causes of Disease.

Describe exogenous causes of disease

A

Disease caused by injury from an agent acting externally.

Divided into 3 groups:

  • physical - trauma, heat/cold, electricity, atmospheric pressure, radiation.
  • chemical - subdivided into:
    • poisoning - accidental, homicidal, suicidal
    • drug reactions - toxic effects of prescription or proprietary drugs taken to treat disease
  • microbiological - known as INFECTIONS - classified by the type of the offending organism:
    • bacteria
    • fungi
    • rickettsiae
    • viruses
    • protozoa
    • helminths
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15
Q

Causes of Disease.

Describe endogenous causes of disease

A

3 large categories:

Vascular diseases:

  • obstruction of blood supply to an organ or tissue, ie. myocardial Ischemia secondary to atherosclerosis.
  • haemorrhage, ie. ruptured abdominal aortic aneurism.
  • altered blood flow, ie. microvascular changes in diabetes or hypertension.

Immunologic diseases:

  • caused by anomaly of the immune system.
  • failure of the immune system to work when needed results in immunodeficiency disease.
  • overreaction of the immune system causes allergic, or hypersensitivity diseases.
  • abnormal reaction of the immune system to endogenous substances causes autoimmune diseases.

Metabolic diseases:

  • encompasses wide variety of biochemical disorders that may be genetically determined or secondary effects of acquired disease.
  • most commonly categorised as abnormalities that primarily involve lipids, carbohydrates, proteins, minerals, vitamins and fluids.
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16
Q

Causes of Disease.

List other causes of disease

A

Some diseases cannot be classified due to internal/external causes, as the cause is unknown.

Disease of unknown cause is termed Idiopathic.

Adverse reactions resulting from treatment by a HCP produce Iatrogenic disease.

Diseases acquired from a hospital environment are termed Nosocomial.

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17
Q

Manifestation of disease.

Define Manifestation of Disease.

A

This refers to all the data gathered about a disease as it occurs in a patient.

The manifestations that are of interest to a HCP are:

  • symptoms
  • signs
  • laboratory findings/abnormalities
  • diagnosis
  • syndromes
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18
Q

Manifestation of Disease.

Define symptoms

A

Evidence of disease perceived by the patient such as:

  • pain
  • a lump
  • diarrhoea

HCP’s will record these as the patients ‘History’

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19
Q

Manifestation of Disease.

Define signs

A

Physical observations made by the person examining the patient, such as:

  • tenderness
  • a mass
  • abnormal heart sounds

These are observed and recorded as a ‘physical examination’

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20
Q

Manifestation of Disease.

Define laboratory findings/abnormalities

A

Observations made by the application of tests or special procedures, such as:

  • x-rays
  • blood counts
  • biopsies
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21
Q

Manifestation of Disease.

Define diagnosis

A

The process of assimilating the information from the symptoms/history, the signs/physical examination and the laboratory findings in order to identify the condition causing the disease.

Also refers to the name given to that disease, ie. diabetes.

It sums up all essential information from the symptoms, signs and lab findings so that a prognosis can be given and appropriate treatment started.

Diagnosis and treatment, is of course the assumption that diseases of the same name will run a predictable course, that may be altered by medical intervention.

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22
Q

Manifestation of Disease.

Problems with diagnosis

A

Sometimes diagnosis cannot immediately be made, ie. alzheimer disease cannot be definitively diagnosed until a patient’s brain is examined after their death.

In these cases, whilst the patient is alive, they are given a provisional diagnosis, ie. Alzheimer-type dementia.

Rheumatologic, neurologic or gastrointestinal diseases may also be vaguely identified(eg. Paralysis of unknown cause) and treated symptomatically until the disease ‘declares itself’ or develops features that will allow its unique identification.
In these cases the clinical problem(eg. paralysis, dementia) becomes the focus of treatment until the disease becomes identifiable.

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23
Q

Manifestation of disease.

Define syndromes

A

Clusters of findings that are commonly encountered with more than one disease.
For example:
- Leakage of protein into the urine
- low serum protein
- oedema
These are all common findings in the ‘nephrotic syndrome’ which can be caused by a number of different diseases that affect the renal glomeruli.

The syndrome describes a group of symptoms, for which treatment can be started, to alleviate the symptoms.

However specific treatment of the disease causing the syndrome will still be necessary.

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24
Q

Injury, Inflammation and Repair.

Review events following injury

A

In varying proportions involve:

Necrosis

  • the death of cells or tissue as a result of endogenous or exogenous injury
  • mild forms of injury may produce sub lethal cell injury without necrosis, referred to as degeneration.
  • lethal and sub lethal cell injury occur together in varying proportions.

Inflammation

  • the vascular and cellular response to necrosis or sub lethal cell injury.
  • the body’s mechanism of limiting the spread of injury and removing necrotic debris.

Repair
- the body’s attempt to replace dead cells, whether by regeneration of the original tissue or replacement by connective tissue.

Relative intensities of necrosis, inflammation and repair depend on:

  • magnitude and/or duration of injury
  • location within the body
  • nature of the injury

Generally inflammation begins immediately after cell injury.
Repair is not usually well established until necrosis ceases.
In chronic injuries all 3 processes might occur together.
Intense inflammation can cause necrosis, the body may sacrifice some of its own tissue to isolate and agent of injury.

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25
Q

Injury, Inflammation and Repair.

Describe apoptosis

A

Often referred to as ‘programmed cell death’.

Not necessarily an indication of injury.

Occurs for example during embryogenesis, when not all cells generated are required.

Mechanism for:

  • ridding the body of excess lymphocytes following resolution of an inflammatory or immune event.
  • hormone-dependant cell death after the hormonal stimulus is removed.
  • tumour cell death.

May also occur following injury a variety of agents that might cause necrosis under other conditions.

Referred to as ‘programmed’ as it results from the activation of specific genes following appropriate stimuli.

Differs in appearance from necrosis:

  • cell shrinks
  • nuclear chromatin condenses into dense masses
  • blebs form in the cytoplasm
  • the apoptotic cells then phagocytosis by macrophages or nearby parenchymal cells

Apoptosis does not elicit inflammation.

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26
Q

Injury, Inflammation and Repair.

Review Acute injury and Necrosis

A

Acute injury most prominently affects cells, as cells are more susceptible to injury than non-cellular connective tissue elements.

The critical difference between sublethal(reversible) cell injury and necrosis is whether the cell can recover or is dead.

Certain changes in cell nucleus indicate cell death. Nuclear changes include:

  • pyknosis - condensation of the nucleus
  • karyorrhexis - fragmentation of the nucleus
  • karyolysis - lysis/fading of the nucleus

These changes may take a number of hours to develop, so cells may not show these changes immediately even though they are dead.

Reversible cell injury is characterised by the preservation of the nucleus and variable changes in the cytoplasm such as swelling/condensation of the cell, nucleus and/or cytoplasmic organelles.
These changes reflect the biochemical changes in the cell.

There is no exact biochemical end point that determines cell death, but depletion in the cell’s energy system(especially ATP) and alteration of the cell membranes permeability are critical events leading to death of a cell.

Once the nucleus is destroyed or the cell membrane disrupted, the cell cannot recover.

After cell death, enzymes released from the cells own lysosomesbegin to digest the remains of the cell.

Other events associated with necrosis:

  • influx of calcium
  • dissolution of ribosomes
  • clumping of DNA followed by its enzymatic digestion
  • rupture of the cell membrane(final element)
  • the above changes will elicit an inflammatory response(necrotic tissue is a potent stimulus of inflammation)

In summary:

  • when reversible changes predominate, a tissue will be enlarged
  • when necrosis predominates, a tissue will be of normal size or shrunken

Necrotic tissue takes on differing gross and microscopic appearances dependant on circumstances.
Recognition of these differences can suggest the cause of necrosis.

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27
Q

Injury, Inflammation and Repair.

Describe free oxygen radicals

A

Unstable oxygen molecules that have only a single unpaired electron in their outer orbit.

Generated by the reduction of molecular oxygen to water.

Partial cause of many types of cell injury.

React with proteins, lipids and carbohydrates, releasing energy that when generated damages DNA and vital cell structures such as membranes.

28
Q

Injury, Inflammation and Repair.

Discuss types of acute injury and necrosis - Anoxia/Hypoxia

A

One of most common causes of Acute injury and necrosis:
Anoxia-lack of oxygen
Hypoxia-reduction of oxygen

Cells are vulnerable to hypoxia in proportion to their oxygen requirements, thus, metabolically active cells are selectively vulnerable. This is illustrated by systemic anoxia from causes like carbon monoxide poisoning, blood loss or suffocation.

In these situations, neurons in the brain and the kidneys tubular epithelial cells are more vulnerable to necrosis than any other kind of cell.

Localised hypoxia resulting from poor blood flow is termed ischemia.

When severe, ischemia leads to necrosis of the cells in the area of the compromised blood supply.

An area of ischemic necrosis is termed an infarct.

Infarcts are most commonly obstruction of arteries. Atherosclerotic plaques that obstruct coronary arteries, lead to myocardial infarcts and are responsible for high no.s of deaths.

Atherosclerotic obstruction is also key in producing infarcts of the brain, legs, kidneys and other sites.

29
Q

Injury, Inflammation and Repair.

Discuss types of acute injury and necrosis - Thrombi/Emboli

A

Important causes of ischemic necrosis.

Thrombus is a blood clot that forms during life in a blood vessel, as a result of activation of the coagulation process.
Composed of layers of fibrin and entrapped blood cells.

An Embolus is any particulate object that travels in the bloodstream from one site to another.
Most commonly arises from a thrombus but can be other substances such as:
- bone marrow
- fat
- air
- cancer tissue
Thrombotic emboli most commonly originate in the legs veins, travel through the vena cava and right heart to the pulmonary arteries, or from the left heart through the aorta to various organs such as:
- brain
- legs
- kidneys
- spleen
- intestines

Bone marrow and fat emboli occur after trauma to bones, when severe the fat globules pass through pulmonary vessels and gain access to the systemic circulation, where they can cause obstruction of the small vessels of the brain.

30
Q

Injury, Inflammation and Repair.

Discuss types of acute injury and necrosis - Trauma/Infection/Hypersensitivity

A

Trauma disrupts cells by direct physical force, effects are dependant on the site injured and the nature of the force being applied.

Although there are many types of infections and the degree of injury varies widely,most damage is produced by the body’s own inflammatory response to the invading microorganism.
Immunologic mechanisms are important in the inflammatory response and also contribute to the damaged caused by the inflammation, although the immune damage is usually less than the potential damage that could be inflicted by the offending agent.

When an immunologic reaction occurs in sensitised individuals only, the reaction is referred to as a hypersensitivity reaction /allergy.
Common examples are:
- hay fever
- hives
- contact dermatitis

Sometimes the body will react to its own tissues, known as an Autoimmune Reaction.
This produces destructive diseases such as:
- rheumatoid arthritis
- lupus erythematosus
- thyroiditis

31
Q

Injury, Inflammation and Repair.

Identify Coagulation Necrosis

A

Most commonly caused by Anoxia, whether it be generalised or ischemic.

In many tissues, coagulation evolves slowly, over days. This produces characteristic preservation of cell and tissue outlines until later stages of the process.

The coagulation necrosis of an infarct can be recognised by its pale yellow colour and solid, but soft texture.

The location, size and shape of the infarct depend on the area being supplied by the blocked artery.

32
Q

Injury, Inflammation and Repair.

Identify Liquefaction Necrosis

A

Most commonly caused by certain types of bacteria known as Pyogenic Bacteria.

These pyogenic bacteria attract neutrophils into the area they release enzymes to liquefy the dead tissue.

The resultant thick, creamy mixture of dead tissue and neutrophils is called Pus/Purulent Exudate.

When cut into, an area of liquefaction necrosis will exude pus and leave a hole in the tissue.

33
Q

Injury, Inflammation and Repair.

Identify Caseous Necrosis

A

Most commonly caused by Mycobacterium Tuberculosis, the bacterium that causes Tuberculosis, or by certain Fungi.

Caseous necrosis looks different as it is necrosis of diseased tissue.

The causative organisms are attacked by large no.s of lipid-containing macrophages.

Necrosis of these macrophages produces a solid, amorphous, cheesy mass.
Microscopically, a mass of red cytoplasm with scattered nuclear dust remains.

Special staining techniques can be used to reveal the causative organisms in this material.

34
Q

Injury, Inflammation and Repair.

Identify Enzymatic Fat Necrosis

A

Occurs following injury to the pancreas and surrounding adipose tissue, as a result of the organs digestive enzymes leaking.

Produces chalky, yellow-white nodules resembling caseous necrosis.

The location is limited to the pancreas and it’s surrounding.

35
Q

Injury, Inflammation and Repair.

Identify Gangrenous Necrosis(Gangrene)

A

Coagulation necrosis with superimposed decomposition by saprophytic bacteria.

Similar to postmortem decomposition except that only a portion of the body is dead.

In Gas Gangrene, however, organisms causing the gangrene include a strain of bacteria of the genus Clostridium, which produces gas and a necrotising toxin.
The toxin of gas gangrene can spread to normal tissue and produce lethal effects.

36
Q

Injury, Inflammation and Repair.

Describe Chronic Injury

A

May produce:

  • ATROPHY(a decrease in tissue size)
    • may be result of a decrease in the size of cells, in the no. of cells, or both
    • is most commonly a gradual loss of cells

Or

  • ACCUMULATION(of material within or between cells)
    • often cells slowly accumulate their own metabolic products or exogenous materials, resulting in a decrease in cell function
    • can result in enlarged cells, with decreased function

Types of chronic cell or tissue degeneration are classified according to the cause of the atrophy or the type of material accumulated.

37
Q

Injury, Inflammation and Repair

Identify types of Atrophy - Senile Atrophy

A
  • Caused by aging
  • tissues often become smaller and decrease in functional capacity
  • natural part of aging process

Eg. Brains of aging people become smaller, whilst decreased memory and slowed thought processes provide evidence of decreased cellular function.

38
Q

Injury, Inflammation and Repair

Identify types of Atrophy - Disuse Atrophy

A
  • occurs when cells are unable to carry out their normal function
  • may be reversible

Eg. When an arm/leg placed in a cast, muscle cells gradually become smaller and show decreased ability to contract. Once cast is removed, and the limb exercised, the strophic muscle cells can regain their prior function and structure.

39
Q

Injury, Inflammation and Repair

Identify types of Atrophy - Denervation Atrophy

A
  • muscle cells are immobilised due to permanent loss of nervous stimulation

Eg. After traumatic severance of a nerve, muscle cells will remain atrophied.

40
Q

Injury, Inflammation and Repair

Identify types of Atrophy - Pressure Atrophy

A
  • results from steady pressure on tissues, such as could be produced by the mass of an expanding tumour

Eg. Bedsores, they occur in bedridden patients due to external pressure on the skin.

41
Q

Injury, Inflammation and Repair

Identify types of Atrophy - Endocrine Atrophy

A
  • resulting from decreased hormonal stimulation
  • certain organs are maintained in their functional state by the action of hormones upon them
  • insufficient hormonal stimulation results in atrophy of the organ

Eg. The decrease in estranged and progesterone at the time of menopause results in atrophy of the breasts and uterus.

42
Q

Injury, Inflammation and Repair.

Briefly Describe Inflammation

A

Protective response that the body mounts in response to injury.

The term reflects the observation that an inflamed lesion is like fire: red, hot and painful.

A process by which fluid, chemicals and cells are brought to an injured area to limit the extent of the injury, remove necrotic debris, and prepare for the healing process.

Involves complex chemical, and to a lesser extent, neural mechanisms that serve to turn on the response quickly and mobilise more reserves.
And also to turn the process off in order that the cellular and chemical responses don’t destroy any more normal tissue than is necessary to control the spread of injury.

The degree and duration of the inflammatory response vary depending on the cause and time course of the injury.

Described as a protective response, but also has damaging effects.

43
Q

Injury, Inflammation and Repair.

Define Acute Inflammation

A

Tightly coordinated vascular and cellular responses to injury.

Vascular response results in increased blood flow to the injured area, and increased vascular permeability so that water, electrolytes and serum proteins leak into the tissue spaces.

The cellular response refers to the movement of leukocytes, predominantly neutrophils and monocytes, from the blood, into the tissue.

This cellular response produce the the ‘cardinal signs of inflammation’:

  • redness - hyperaemia
  • swelling - oedema
  • heat - hyperaemia
  • pain - oedema
  • loss of function - resulting from the attempt to protect the painful, swollen lesion from further injury

Cellular response refers to movement of leukocytes, mainly neutrophils and monocytes, from the blood into the tissue.

Inflammation destroys or limits the spread of the causative agent, and cleans up debris in preparation for the repair process.

In simple injuries, like a burn, cut or chemical injury where the chemical has been diluted away, the causative agent is no longer a threat therefore the inflammatory response is proportional to the amount of tissue damage.

Tissue damage itself incites a mild inflammatory response, enough to bring leukocytes to digest and remove the debris from the dead cells and increase lymph flow to carry away fluid from the lesion.

Both neutrophils and macrophages engulf particulate matter, aprocess known as phagocytosis.

Microscopically Acute inflammation is characterised by the presence of abundant neutrophils, usually intermixed with macrophages.

44
Q

Define hyperaemia

A

Increased blood flow in dilated vessels, causing redness and heat.

45
Q

Define oedema

A

Leakage of fluid into the tissues, causes swelling and pain(pressure)

46
Q

Describe cellular events during inflammation

A

Phagocytes(neutrophils and macrophages) play a key role in the inflammatory process, moving from their normal location in the bloodstream to the periphery as the venule dilates and the flow of blood slows, referred to as ‘margination’.

The marginated leukocytes then stick to endothelial cells, due to complementary molecules on the leukocytes and endothelial cells being activated by chemical mediators of the inflammatory process, referred to as ‘adhesion’.

Once chemically stuck to the endothelial cell, the leukocytes crawl between the endothelial cells, into the tissue, known as ‘emigration’.

47
Q

Discuss the action of neutrophils during the cellular response to inflammation

A

Neutrophils migrate fastest from the vessels to the injured site, arriving within minutes and accumulating over hours.

Neutrophils may die soon after arrival at the injured site in order to liberate their powerful digestive enzymes, or they may phagocytose and digest cellular debris and foreign material before dying.

Once at the site of an infection neutrophils rapidly phagocytose the offending agent, including bacteria, which can be responsible for large numbers of infections because many are part of the natural flora of the skin, mouth, resp. Tract and intestines. Neutrophils detect and move toward certain chemicals found in bacteria by the process of ‘chemotaxis’ - the movement of white blood cells in relation to a chemical gradient. This can be in response to chemicals released by bacteria or to ‘chemokines’(small proteins produced by the body itself/endogenously during inflammation).

Bacteria have evolved mechanisms of resisting phagocytosis, such as thick polysaccharide capsule that evade the detection mechanisms of the host.
The host can counter this by producing antibodies known as ‘opsonins’ that attach to this capsule and are easily recognised by phagocytes.

Opsonins are important in the response to organisms that have been encountered previously or when antibodies have been artificially induced by immunisation.

The rapid neutrophil reaction to bacteria often result in the death of many neutrophils and much tissue breakdown to produce pus, giving rise to the organisms being referred to as ‘pyogenic’ or ‘pus forming’.

48
Q

Discuss the action of macrophages during the cellular response to inflammation

A

Macrophages are slower moving and peak later than neutrophils.
Although they arrive later, they are hardier than neutrophils and carry the major load when cleaning up the inflammatory debris, including the dead neutrophils.

49
Q

Neutrophils and macrophages-in relation to injury

A

Numbers of neutrophils and macrophages depend on the amount and nature of the dead tissue, and whether highly chemotactic foreign substances, like pyogenic bacteria, are present.

For example a staphylococcal infection will have lots of neutrophils, whereas injured adipose tissue from trauma has mostly macrophages to remove the spilled lipids. Macrophages also predominate in reaction to large inert foreign particles such as suture material, surrounding the material and often forming multinucleated giant cells which often remain in the tissue for long periods of time.

Phagocytosis by neutrophils and macrophages entails sequestration of the engulfed particle, whether bacterium or foreign material, into acytoplasmic compartment where killing occurs, mainly by the action of free oxygen radicals such as:

  • hydrogen peroxide(H2O2)
  • hydroxyl halide(HOCl-)
  • nitric oxide(NO)-
  • hydroxyl ions(HO)

The particles are then digested following the release of enzymes.

50
Q

Discuss the role of noncellular elements in inflammation

A

Increased fluidity of of the lesion allows movement of cells and chemicals and promotes increased flow of lymph to carry fluid debris away from the injured area.

It may also serve to dilute offending agents like toxins and antigens.

Fibrinogen is a soluble blood protein that may leak into the inflamed site and be converted into a stringy polymer known as ‘fibrin’. This process involves several enzymes and is activated by exposure to damaged tissue.

Formation of fibrin serves as a barrier to prevent the spread of injury, ie. a scab - formed of fibrin, keeps bacteria out, keeps fluid in.

Fibrinogen is a large protein, so only leaks into tissue during severe increase in vascular permeability, and even then, some of the fibrin formed is lysed by the enzyme fibrinolysin.
These control mechanisms prevent the formation of fibrin in mild injuries for which it is not needed.

51
Q

Summarise the importance of the inflammatory reaction

A

Patients who lack the ability to mount an acute inflammatory reaction will succumb to infections that are easily warded off by people with an intact inflammatory response mechanism.

Acute Inflammation can also be very damaging, so its control is important. It must be activated quickly and turned off when no longer required.

52
Q

Define Repair

A

The body has 2 basic methods of repair following tissue destruction which are:

  • regeneration
  • fibrous connective tissue repair(scarring or fibrosis)

Many tissue injuries heal in part by regeneration and in part by fibrosis.

53
Q

Define Regeneration

A
  • the replacement of destroyed tissue by cells similar to those that were previously present, eg. Epidermal surface of a cut is replaced with epidermis,fractured bone is united by bone.
  • restores normal tissue function and so is more desirable, in particular when there has been widespread damage to a vital organ.
  • A pre-requisite of regeneration Is that the cells directly next to those that have died must be able to multiply.
  • some cells, like neurons and cardiac muscle fibres, do not undergo cell division as adults, so annoy regenerate after injuries,eg. Prolonged hypoxia of the brain(neuronal tissue) during cardiac arrest with successful resuscitation.
  • in contrast, tissue that is constantly replacing its cells under normal conditions, like that of the epidermis, G.I. Tract, or bone, have a much greater capacity for regeneration.
  • regeneration can repair defects of the epidermis or intestinal mucosa that are several centimetres in diameter. Bone marrow can replace itself even when only a few cells survive an injury-its capacity for this function is exploited in bone marrow transplants.
  • most tissues of the body undergo cell replacement at a slow rate.
  • regeneration can usually occur in parenchymal organs so long as its architectural framework is still intact.
  • complex structures composed of inter relating tissue types, like the gas exchanging membranes of the lungs, do not regenerate.
54
Q

Define Fibrous Connective Tissue Repair(Scarring or Fibrosis)

A
  • the tissue that was previously present is replaced by fibrous tissue(scar), eg dermal edges of a cut are united by scar, bone fractures not properly united are healed with scar tissue.
  • can occur in any tissue, and produce the same result regardless of site-the formation of a dense, tough mass of collagen known as a scar.
  • does not restore original tissue function.
  • purpose is to provide a strong bridge across the damaged area.
  • process also known as ‘organisation’ and consists of 2 stages:
    • a granulation tissue stage
    • scar forming stage
  • granulation tissue consists of capillaries and fibroblasts.
  • repair initiated by the ingrowth of capillaries and fibroblasts into the injured area.
  • capillaries bring blood to provide nutrition for the repair process, and carry away liquid remains of dead tissue and particulate material removed by macrophages. This removal process is known as ‘resolution’.
  • fibroblasts proliferate rapidly, then initiate the scar formation stage by laying down collagen.
  • initially there is only small amounts of loose collagen amongst the mass of capillaries and fibroblasts. With time, more collagen is formed and the numbers of capillaries and fibroblasts decreases.
  • the final stage, which takes weeks to months, involves the shrinking and condensation of the fibrous scar.
55
Q

Define wound repair

A
  • process artificially separated into repair by primary union and secondary union, depending on whether the wound edges are placed together or left separated.
  • one of the greatest impediments to healing and wound repair is the amount of dead tissue and foreign material present, and It could take the body’s inflammatory cells months to phagocytose large amounts.
  • the presence of bacteria in a wound may produce necrotic tissue and inflammatory cells, as fast as they are being removed, therefore the care of a large wound should always include thorough cleaning and ‘debridement’ (removal of foreign material and necrotic tissue).
56
Q

Define primary union

A
  • minimal tissue damage and edges of wound are brought together (eg. Tape/sutures).
  • The narrow space between the edges of the wound fills with a small amount of serum, which Quickly dries and clots, forming a scab.
  • Within 1/2 days the narrow area of acute inflammation at the edges of the wound has lessened and new capillaries begin to bridge the gap across the defect. By now the epithelium has already grown across the curvaceous the gap.
  • Within a few more days, fibroblasts grow across the subepithelial portions of the wound and begin to deposit collagen, which eventually contracts, pulling the wound edges together and giving them strength.
  • The wound might appear well healed by approx. 2 weeks but may take a month or more for the strength of the scar tissue to approximate that of the original tissue.
57
Q

Define secondary union

A
  • same basic process as primary union except there is greater injury with consequent greater tissue damage and more inflammation to resolve.
  • wound edges not brought together.
  • to fill the larger void There is a tremendous proliferation of capillaries and fibroblasts, which actually start growing after the injury is just a few days old, and acute inflammation may still be intense.
  • after a week or more the wound will be filled with granulation tissue, composed largely of capillaries, fibroblasts, variable numbers of residual acute inflammatory cells, and some chronic inflammatory cells.
  • this tissue is red and oozes blood, eg. Picked off a scab.
  • granulation tissue is eventually replaced as more and more collagen is deposited by fibroblasts.
  • fibroblasts and collagen have inherent contractile properties, these aid in shrinking a wound and drawing the edges together.
  • it may take a long time for a wound healing by secondary union to achieve strength approximate to that of the original tissue.
  • if a skin wound is very large, the epithelium may never completely bridge the wound, and skin may need to be grafted to the site from another area of the body. Transplanted skin usually grows quite readily in such situations as the underlying granulation tissue is so rich in capillaries.
58
Q

Explain the interaction between antibodies and antigens in the immune response

A

B lymphocytes(B-cells) are a form of white blood cell descended from stem cells.

Each B-cell makes antibodies that have only 1 type of antigen-binding region, and therefore are specific for a particular antigen, known as the cognate antigen.

Antibody molecules are found on the surface of B-cells, where they are able to recognise the presence of their cognate antigens.

For B-cells to to produce antibodies, they must first be activated, most commonly by ‘helper’ T lymphocytes(T-cells):

a macrophage engulfs the antigen via phagocytosis, digesting it and pushing the discarded particles to the cell surface. These remnants interact with the B-cell and the helper T-cell.

the antigen binds to the B-cell and the T-cell, activating them both.

the activated T-cell secretes a lymphokine, a substance that stimulates the B-cells to produce a clone(a group of identical cells formed from the same parent cell.

an intermediate cell called a lymphoblast is produced.

The lymphoblasts divide/clone, producing plasma cells and memory B-cells.

The plasma cells produce antibody molecules.

The memory B-cell is left to enable a more rapid response to another attack/stimulation by the same antigen.

Antibodies act as ‘opsonins’, coating an antigen, allowing it to be recognised by immune cells. Antibodies themselves are not toxic, but they label antigens in order that immune cells know to attack them.

Antibodies cause antigens to clump together for easier phagocytosis(precipitation/agglutination).

Antibodies can bind to and deactivate some toxins produced by bacteria, allowing macrophages to ingest and destroy the deactivated toxin.

59
Q

Explain the role of white blood cells in the immune response

A

WBC’s are the primary cells of the immune system. They can be broken down into 5 general types:

Basophils.

  • contain histamine granules and other substances released during inflammatory and allergic responses.
  • account for less than 1% of leukocytes but are essential to the nonspecific immune response to inflammation because they release histamine and other chemicals that dilate blood vessels.

Eosinophils.

  • release substances that damage or kill parasitic invaders.
  • also play a major role in mediating the allergic response.
  • account for 1%-6% of leukocytes.
  • release chemoactive substances that can result in severe bronchospasm.

Neutrophils.

  • the most abundant of the WBC’s, accounting for 40%-75% of leukocytes.
  • have a segmented nucleus and are often called polymorphonuclear leukocytes(“polys”).
  • largely responsible for protecting the body against infection and are key components of the first response to foreign body invasion.
  • readily attracted by foreign antigens, which they destroy by engulfing and digesting(phagocytosis).

Monocytes.

  • mature in the blood during their first 24 hours, then travel to the tissues, where they differentiate into macrophages.
  • macrophages function primarily as scavengers for the tissues.
  • monocytes and macrophages represent Oe of the first lines of defence in the inflammatory process.

Lymphocytes and their derivatives.

  • mediate the acquired immune response.
  • although most lymphocytes are found in the lymphoid tissues, many are found in circulating lymph and blood as well.
  • there are 2 basic types: B lymphocytes and T lymphocytes.

Mast cells resemble basophils but do not circulate in the blood. they are found in the connective tissues under the skin, in the gastrointestinal mucosa and in the mucosal membranes of the respiratory system.

Mast cells play a role in allergic reactions, immunity and wound healing.

60
Q

Describe the pathophysiology of allergy in relation to the immune response

Primary response

A

When a foreign substance invades, the body initiates a series of responses.

The 1st encounter with a foreign substance begins the primary response:

  • macrophages immediately confront and engulf the invader to determine if they are allowed in the body
  • if the body is unable to identify the substance, it uses the immune cells to record the notable features of the outside substance
  • the immune cells record 1 or 2 of the proteins on the surface of the substance the design specific proteins to match each substance
  • these proteins, known as antibodies are intended to match up with the invader/antigen and deactivate it

Through the primary response, the body develops SENSITIVITY - the ability to recognise the foreign substance if it is encountered again.

In order to determine whether the substance is ‘one of us’, the body records enough details to assist in future identification of it, and produces antibodies which perfectly fit it, these are then distributed to the rest of the body by placing the specific antibodies on Basophil and Mast cells.

Basophils are stationed in specific sites within the tissues.

Mast cells move through the connective tissues, brooch, gastrointestinal mucosa and other vulnerable border areas that act as barriers to foreign invaders.

61
Q

Define Allergen

A

An antigen that produces an abnormal immune response, causing allergic symptoms in a patient.

Most are usually harmless substances that pose no threat to most people, eg. milk, eggs, nuts

62
Q

Describe the pathophysiology of allergy in relation to the immune response

Chemical Mediators

A

The body’s chemical weapons, they launch and maintain the immune response, produced by the Basophils and Mast cells.

These cells contain granules filled with a host of powerful substances, ready to be released, to fight invading forces of antigens.

As long as the body is not invaded by a previously identified foreign substance, the granules remain encapsulated in their protective walls, and remain inactive.

If an antigen invades the body and combines with one of the antibodies, however, the granules are ejected from the Mast cells and are then detonated, releasing the chemical mediators into the surrounding tissue and the bloodstream.

Chemical mediators:

  • summon more white blood cells to the area, to fight the invading substance
  • increase blood flow to the area under attack by dilating the blood vessels and increasing capillary permeability
  • these actions are useful when a small invasion occurs in a limited area, but can be extremely dangerous they spread throughout the body.
  • when they have systemic effects, the chemical mediators cause the signs and symptoms of the allergic and anaphylactic reactions seen in the body
63
Q

Chemical mediators and their effects

A

Histamine:

  • systemic vasodilation
  • increased permeability of blood vessels
  • decreased cardiac contractility
  • arrhythmias
  • bronchoconstriction
  • pulmonary vasoconstriction

Eosinophil Chemotactic Factor:
- attracts eosinophils and neutrophils

Arachidonic Acid(precursor to the following - Prostaglandin, Leukotrienes, Platelet Activating Factor, Serotonin):

  • smooth muscle contraction
  • vascular permeability
  • bronchoconstriction
  • decreased force of cardiac contraction
  • decreased coronary blood flow
  • arrhythmias
  • platelet aggregation
  • causes histamine release
  • pulmonary vasoconstriction

Proteoglycans(Heparin, Chondroitin Sulphate, Chemokines, Cytokines):

  • control the release of Histamine, these mediators as a whole work to activate the Kinin system and are thought to contribute to prolonged and biphasic reactions
  • trigger inflammatory pathways and increase the recruitment of inflammatory cells

Kinins:
- Bradykinin is one of the stronger kinins and is responsible for increased vascular permeability

64
Q

Describe the pathophysiology of allergy in relation to the immune response

Secondary Response/immunity

A

occurs when the body has previously been exposed to a foreign substance, and the matching antibodies already exist to fight it.

A cell carrying the antibody encounters and recognises the foreign substance and an intense immune response is triggered.

Large no.s of antibodies and immune cells are sent to the area, to destroy the foreign substance.

65
Q

Define Acquired Immunity

A

The administration of a vaccine, allows the body to produce the antibodies without having to experience the disease.

66
Q

Define Natural Immunity

A

The body encounters an antigen, and experiences a full immune response to the disease.

The body suffers the signs and symptoms of the disease, but then has the antibodies to fight off another encounter.

Ramp - Pathophysiology (10 decks)

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