Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology > B1 > Flashcards

B1 Flashcards

1
Q

Describe necrosis

A
  • More common type of cell death
  • Occurs after exogenous stimuli ex : stress & chemical injury
  • Always pathological
  • Inflammation always present
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe apoptosis

A
  • A form of genetically programmed cell death designed to eliminate unwanted host cells through activation of a coordinated series of events
  • can be either physiological or pathological
  • no inflammation , plasma membrane remains intact ( hence no leakage of lysozymes , no enzymatic digestion )
  • fragments of apoptosis cells break off & become targets of phagocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

State the manifestation of necrosis of cell

A

I) severe cell swelling / cell rupture
II) denaturation and coagulation of cytoplasmic proteins
III) Breakdown of cell organelles

  • Inflammation
  • Leakage of lysozymes causing enzymatic digestion of cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Mention some causes of cell injury

A

1) Oxygen deprivation
- Hypoxia , ischemia
- ischemia is more severe because it causes both lack of oxygen and nutrient supply

2) Physical agents
- burns & trauma

3) Chemical agents & drugs
- Glucose , salt , water , insecticides , asbestos

4) Nutritional imbalances
- vitamins & minerals

5) Genetic derangement
- genetic mutation ex: sickle cell anemia

6) Infectious agents
- Virus , parasites , bacteria

7) Immunologic agents
- Autoimmune response , hypersensitivity reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

State 2 phenomena which consistently characterise irreversible cell death

A

1) Inability to reverse mitochondrial dysfunction
- Causes marked ATP depletion

2) Development of profound disturbances in membrane function
- Cell membrane become destroyed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the morphology of reversible cell injury ( general & ultrascopic )

A

General

1) Cellular swelling ( hydropic change / vacuolar degeneration )
- Due to accumulation of H2O as a result of impaired Na & K regulation on the cell membrane
- Damage to cell membrane —> impair ATP- dependent processes , Na+ into cell , K+ out —>H2O follows NA into cell
- First manifestations of cell injury

2) Accumulation of triglycerides in the intracellular parenchyma / accumulation of fat vacuoles in the cytoplasms of hepatocytes ( Fatty changes )
- Nucleus of hepatocytes displaced to the periphery
- presence of lipid vacuoles histologically
- in gross morphology , organ may become enlarged ( increase turgor ) , pallor ( due to compression of capillaries ) and have increased weight , greasier
- More common in organs participating in fat metabolism (liver , heart , kidney )
- Ex. In liver , fatty changes is secondary to alcoholism , diabetes mellitus , malnutrition , obesity or poisoning

Ultrascopic

1) Plasma membrane alterations
- blebbing , blunting & distortion of microvili

2) Mitochondrial changes
- swellings , rarefraction , amorphous densities

3) Dilatation of ER
- detachment & disaggregation of polysomes

4) Nuclear alterations
- disaggregation of granular &fibrillation elements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the morphology of irreversible cell injury

A

1) Severe swelling of mitochondria
2) Extensive damage to plasma membrane
3) Swelling of lysosomes , followed by leaking their enzymes into the cytoplasm & activation of their hydrolases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

State & briefly describe the biochemical mechanism of cell injury

A

1) ATP depletion
- Lack of oxygen /nutrients in hypoxia / ischemia / mitochondrial damage / toxins
- Causes decreased activity of plasma membrane ATP - dependent pumps , increased in anaerobic glycolysis causing increased lactic acid accumulation , influx of Ca due to failure of Ca pump , structural depletion of protein synthetic apparatuses

2) Mitochondrial damage
- mitochondria sensitive to injurious stimuli
- Causes reduced oxidative phosphorylation & ATP , causes release of ROS, release of mitochondrial proteins into cytosol causes apoptosis

3) Influx of calcium & loss of calcium homeostasis
- Ca pump disrupted
- causes influx of Ca into cell —> activated enzyme —> cause harm to the cell

4) Accumulation of ROS ( oxidative stress )
- generation of ROS occur due to redox reaction in body , absorption of radiant energy , metabolism of exogenous drugs , nitric oxide , transition metals
- ROS attacks cellular proteins , lipids & nuclei acids

5) Defects in membrane permeability
- Affects membrane-bound organelles (mitochondria , lysosomes and the cell itself
- affects ATP production , causes leakage of lysozymes into cell & alter osmotic balance & leads to loss of cellular content within a cell

6) Damage to DNA & proteins
- accumulation of damaged DNA & misfolded proteins —> apoptosis
- Affects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe Hypertrophy with examples

A
  • Increase in cell size resulting in increase in mass of tissue & organ
  • usually occurring in cells which do not divide
  • can be physiologic or pathological , caused by increased functional demand or by hormones and growth factors
  • physiological : massive growth of uterus during pregnancy , skeletal muscle Hypertrophy due to strength training
  • Pathological : left ventricular Hypertrophy in heart
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe hyperplasia in examples

A
  • increased in number of cells in an organ or tissue , usually resulting in the increased mass of organ or tissue
  • can be pathological or physiological
  • stimulus is increased functional demand , growth hormone , hormonal , growth factors
  • Physiological :
    I) hormonal hyperplasia : - proliferation of granular epithelium of female breast at puberty & pregnancy ( due to increase in estrogen)
    II) compensatory hyperplasia : occurs when a portion of liver is removed
  • Pathological :
    I) endometrial hyperplasia
    II) thyroid hyperplasia —> thyrotoxicosis
    III) Benign prostatic hyperplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe atrophy with examples

A
  • reduced size of an organ resulting from a decrease in cell size & number
  • can be physiologic or pathological
  • Physiological : thymus , uterus after parturition , breast after lactation , embryological ( thyroglossal duct , branchial clefts ) , infancy ( ductus arteriosus , umbilical vessels )
  • pathological : generalized ( extreme starvation , senile atrophy , endocrine atrophy ) ; localised ( ischemic atrophy , pressure atrophy , disused atrophy , neuropathic atrophy )
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe metaplasia with examples

A
  • reversible changes in which one differentiated cell type ( epithelial or mesenchymal ) is replaced by another type
  • most common type of epithelial metaplasia : columnar —> squamous ( squamous metaplasia)
  • types of metaplasia
    I) epithelial metaplasia ( squamous , columnar metaplasia )
    II) CT metaplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

State the example of epithelial metaplasia

A

A) Squamous metaplasia
I) seen in chronic smokers in respiratory tract ( columnar , pseudostratified —> squamous cell)
II) Changes in salivary glands , pancreas & bile duct due to stones
III) renal pelvis & bladder transition from urothelium —> squamous cell in chronic inflammation & renal stones
IV) deficiency in Vit A —> cause metaplasia in respiratory tract

  • columnar metaplasia
    I) Barret’s oesophagus
    II) stomach-intestinal metaplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

State the the example of CT metaplasia

A
  • formation of cartilage , bone or adipose tissue ( mesenchymal tissue ) in tissue that normally do not contains these elements
  • ex: bone forms in muscle ( myositis ossificans)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe dysplasia with examples (characterised by )

A
  • Dysplasia is an abnormality of both differentiation and maturation
  • It is a premalignant lesion associated with increased risk development of cancer
  • Characterized by :
    1) Nuclear abnormalities
  • Increased nucleus size
  • Increased nucleus : cytoplasm ratio
  • Increased chromatin content ( hyperchromasia )
  • abnormal chromatin distribution
  • nuclear irregularities
  • pleomorphism ( multiple morphology )

2) Cytoplasmic abnormalities
- Lack of keratinisation
- Lack of mucin in glandular epithelium

3) Increased rate of mitosis
4) Disordered maturation

5) Basement membrane intact
- cancer basement membrane not intact

6) Lacks of invasiveness vs cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The most common type of epithelial metaplasia is ( …….)

A

The most common type of epithelial metaplasia is ( squamous metaplasia )

** columnar —> squamous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Define necrosis

A

A spectrum of morphological changes occurring after cell death in living tissue , resulting from the progressive degradative action of enzyme on the lethally injured cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

State the types of necrosis

A

1) Coagulative necrosis
2) Liquefactive necrosis
3) Gangrenous necrosis
4) Caseous necrosis
5) Fat necrosis
6) Traumatic fat necrosis
7) Fibrinoid necrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Necrosis is characterised by changes in the cytoplasms & nuclei of the injured cells.Mention the changes

A

Nucleus
I) Pyknosis - progressive shrinkage of nucleus & transformation into a small , dense mass of chromatin which leads to increased Basophilia
II) Karyorrhexis - pyknotic nucleus undergoes fragmentation
III) Karyolysis - breakdown of chromatin & DNA leading to decreased Basophilia

Cytoplasm
I) Increased eosinophilia - due to loss of cytoplasmic RNA & increased binding of eosin to denatured cytoplasmic proteins
II) Glassy & homogenous appearance - due to loss of glycogen particles
III) moth-eaten vacuolated appearance - due to digestion of cytoplasmic organelles

  • basic stain ( hemotoxylin , Basophilic ) binds to nuclei acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe coagulative necrosis ( Pathogenesis ,morphology )

A
  • most commonly seen in hypoxic death
  • Occurs in all tissues ( kidney , heart —> myocardial infarction , adrenal glands) ***except brain
  • Morphology :
    I) general
  • affected area is pale & firm
  • Demarcated from uninvolved tissue by a rim of hyperaemia

II) histological

  • affected cells are eosinophilic ( loss of nuclei acids —> loss of basophilia —> more eosinophilic ) opaque mass w/ loss of nucleus
  • Basic cellular outline & tissue architecture are preserved

-Pathogenesis :injury denatures structural protein & enzymes thereby blocking the proteolysis of dead cells hence the basic structural outline of the cells is preserved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe liquefactive necrosis ( morphology , Pathogenesis)

A
  • seen in hypoxic death of brain tissue , focal bacteria & fungal lesions
  • characterised by digestion of dead cells - transformation into a liquid viscous mass
  • Morphology :
    I) general
  • affected area is soft , liquid , viscous mass
  • if associated w/ acute inflammation , creamy yellow pus is seen

II) histological
- amorphous , acidophilic / eosinophilic fluid w/ complete destruction of cells

  • Pathogenesis :microbes stimulate the accumulation of leukocytes & liberation of enzymes from the cells which liquefy the tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe gangrenous necrosis

A
  • It is coagulative necrosis modified by liquefactive necrosis due to bacterial infection & attracted leukocytes
  • Types :
    I) Dry gangrene : coagulative necrosis is predominant
    II) wet gangrene : liquefactive necrosis is predominant
  • sites : lower leg , appendix , intestine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe caseous necrosis

A
  • seen in foci of tuberculous infection ( lungs , intestine , bone , meninges )
  • morphology
    I) gross
  • affected area appears soft
  • friable ( easily crumble) white cheesy material

II) histology

  • pink , amorphous granular debris enclosed within granulomatous reaction ( soft tubercles )
  • tissue outline completely obliterated & cellular outlines cannot be discerned
  • Pathogenesis : results from hypersensitivity ; lipopolysaccharide present in cell wall of tubercle bacilli
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe fat necrosis

A
  • focal area of fat destruction seen in acute haemorrhagic pancreatitis
  • Morphology :
    I) gross
  • variegated / colourful appearance
  • grayish- white necrotic area in pancreas
  • black haemorrhagic areas
  • amorphous opaque chalky white deposits in pancreas ( fat saponification )
  • Fat globules floating in the asciting fluid

II) Histology

  • Amorphous , granular deposits on the shadowy outline of necrotic fat cells surrounded by inflammatory reaction.
  • Areas of haemorrhage
  • Eosinophillic necrosis areas in pancreatic acini
  • Pathogenesis : results from activated pancreatic lipases into substances of pancreas & peritoneal cavity —> liquefy membrane of fat cells into peritoneum —> triglyceride esters are split —> fatty acids combine w/ calcium to form visible chalky white areas ( fat sponification )
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe traumatic fat necrosis

A
  • due to trauma to superficial adipose tissue eg. Breast

-Morphology :
I) gross
- early : sharply localised lesion
-late : Ill defined induration / lumps

II) late

  • focal area of necrotic fat cells surround by neutrophils & lipid filled macrophages
  • enclosed by fibrous tissue ( spindle shaped cells ) & mononuclear inflammatory cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Describe fibrinoid necrosis

A
  • special form of necrosis seen in immune reactions involving blood vessels ( malignant hypertension , systemic lupus erythematosus)
  • morphology :
    I) histology ( only visible by light appearance )
  • bright pink & amorphous ( fibrinoid ) appearance in H&E stains
  • Pathogenesis : antigen-antibody complexes + fibrin that has leaked out of vessels get deposited on the walls of arteries -> fibrinoid of appearance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Define apoptosis

A

A form of genetically programmed cell death that is designed to eliminate unwanted host cells through a series of coordinated events

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe the mechanism of apoptosis

A

I) intrinsic / mitochondrial pathway
- stimuli : DNA damage , accumulation of misfiled proteins ( ER stress ), lack of growth factors
- activated Bcl-2 family sensors which then activate Bcl-2 family effector ( Bax , Bak ) which are pr-apoptosis proteins
- form channels in the mitochondrial which allow pro-apoptotic mitochondrial proteins such as cytochrome c to escape
- cyt c caspases which breaks down the cell sytoskeleton and activates endonucleases that break down chromatin
- cytoplasmic bless are formed which then separated from the cell to form an apoptosis body
- apoptotic bodies express phosphoatidlyserine & thrombospondin on the cell membrane which then attract macrophages & get phagocytoses
II) Extrinsic / death receptor pathway
- cells express surface receptor ( death receptors ) : TNf & Fas
- receptor- ligand ( eg : FasL on cytotoxic T lymphocytes ) interactions activated adaptor proteins
- the proteins recruit caspases which breakdown the cell cytoskeleton & activates endonucleases that break down chromatin
- cytoplasmic blebs are formed which then separated from the cell to form an apoptotic body
- apoptotic bodies express phosphoatidlyserine & thrombospondin on the cell membrane which then attract macrophages & get phagocytosed

II) Extrinsic / death receptor pathway

  • cells express surface receptors ( death receptors ) : TNF & Fas
  • receptor-ligand ( eg : FasL on cytotoxic T lymphocytes ) interactions activates adaptor proteins
  • the protein recruit caspases which breakdown the cell cytoskeleton & activates endonucleases which break down chromatin.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Compare & contrast necrosis and apoptosis

A

Cell size
N: Swelling
A : Shrinkage

Nucleus
N : Pyknosis -> karyorrhexis -> karyolysis
A : Fragmentation into nucleosome sized fragments

Plasma membrane
N : Disrupted
A : Usually intact , but altered ( especially in orientation of lipids )

Cellular contents
N : Lysosomes leak out enzymes & cause enzymatic digestion of organelles , may even leak out into extracellular space , intracellular proteins denatured
A : Intact , may be released in apoptotic bodies.

Inflammation
N : Present
A : No

Physiologic or pathological role
N : Invariably pathologic ( culmination of irreversible cell injury )
A : Often physiologic ; means of eliminating unwanted cell ; may be pathologic after some forms of cell injury , especially DNA and protein damage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Humans contain ( …….. ) chromosomes , ( …….. ) are autosomal and ( ……..) are sex chromosomes

A

Humans contain ( 46 ) chromosomes , ( 44 ) are autosomal and ( 2 ) are sex chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Distinguish the chromosomal abnormalities of Down syndrome

A
  • Trisomy 21 ( extra copy of chromosome 21 ) hence chromosomal count is 47
  • most common cause is due to meiosis non-disjunction of chromosome 21
  • incidence : 1 in 700 live births
  • maternal age has a strong influence ( occurs in 1 in 25 live births for women > 45 yrs old )

Clinical features
I) mental retardation , 80% have an IQ of 25-50
II) flat facial profile, oblique palpebral fissure , epicanthic folds ( mongolism )
III ) simian crease ( gap b/w 1st and 2nd toe )
IV) Intestinal stenosis
V) Umbilical hernia

32
Q

Distinguish chromosomal abnormalities in Klinefelter syndrome

A
  • male hypogonadism that develops when there are at least 2 X chromosome and 1 or more Y chromosome ( 47 , XXY )
  • due to non- disjunction of sex chromosome during meiosis
  • rarely diagnosed before puberty because testicular abnormalities does not develop before puberty
  • incidence : 1 in 660 male births

Clinical features
i) hypogonadism
II) Elongated body due to increase in length b/w the soles and pubic bone
III) underdeveloped secondary sexual characteristics ( reduced facial , body and pubic hair )
IV) Gynaecomastia
V) Reduced testes size
VI) Low serum testosterone levels w/ elevated urinary gonadotropin and plasma estradiol levels
VII) Commonly infertile due to impaired spermatogenesis

33
Q

Distinguish the chromosomal abnormalities of Turner syndrome

A
  • hypogonadism in females resulting from complete or partial monopsony of X chromosome ( XO ; 45 , X karyotype )
  • incidence : 1 in 3000 live in female birth

Clinical features

  • significant growth retardation —> abnormally short statue
  • failure to develop secondary sexual characteristics ( pubic hair , infantile genitalia )
  • amenorrhea
  • bilateral neck webbing & persistent looseness of skin of the back of the neck
  • most severe cases present during infancy : swelling of the dorsum of the hand , swelling of the nape of the neck producing cystic hygroma
  • congenital heart disease
  • mental status usually normal

** in adults , short statue + amenorrhea —> strong suspicion of Turner syndrome

34
Q

In reversible cell injury , fatty change can be cause any of the following mechanism :

A

1) Decreased use of TAG in cells
2) Increased production of TAG in cells
3) Increased transport of TAG or FA to affected cells
4) Decreased mobilisation of fat from cells

35
Q

Define inflammation

A

A response of vascularised tissue that delivers leukocytes and molecule of host defense from the circulation the site of infection and cell damage in order to eliminate the offending agents

36
Q

Describe the cause of inflammation w/ example

A

1) microbial infections
- eg pyogenic infection , fungi , viruses
- viruses lead to death of cells via intracellular replication , bacteria release specific exo / endotoxins
- some bacteria can cause hypersensitivity reactions ( tubercle bacilli ) which leads to immunologically mediated inflammation
- pathogen-associated molecular patterns (PAMP) of microbes recognised by immune cells w/ help receptors
— pattern recognition receptors ( PRR eg TLR ) -> activate immune cells —> trigger production cytokines & chemokines -> initiate inflammation

2) Hypersensitivity reactions
- occurs when an altered state of immunological responsiveness causes an inappropriate / excessive immune reaction -> damage tissue
- 4 types of hypersensitivity : I, II, III , IV
- eg : tubercle bacilli in tuberculosis , parasites

3) Physical agents
- when cells are damaged -> released self molecules ( mammalian DNA , heat shock proteins ) which acts as an endogenous non foreign alarm signal -> recognised PRR’s —> trigger production of cytokines & chemokines -> inflammation
- eg : physical trauma , ionising radiation , UV , heat , cold

4) Chemical agents
- provoke inflammation through gross tissue damage
- infecting agents —> release chemicals —> directly cause inflammation
- eg : acids , alkalis , corrosive agents , bacterial toxins , reducing agents

5) tissue necrosis
- death of tissue due to lack of O2 or nutrients is a potent inflammatory stimulus
- edge of infarct shows an acute inflammatory response

37
Q

Describe the cardinal signs of inflammation

A

1) Swelling ( Tumor )
- results of accumulation of exudates :
I) edema ( accumulation of fluid in the extravascular space )
II) Physical mass of inflammation cells migrating into the area
III) formation of new CT

2) Redness ( Rubor )
- Due to vasodilation within the damaged area

3) Pain ( Dolor)
- due to stretching & distortion of nerve endings & pain receptors by inflammatory exudates , chemical mediators etc

4) Heat ( Calor )
- due to increased blood flow to the area
- felt only in peripheral part of the body ( skin )

5) Loss of function
- due to pain & restricted movement
- loss of functions may occur due to fibroplasia ( scar tissue ) , metaplasia

38
Q

Describe the classification of genetic disorder

A

1) Disorder related to single gene mutations of large effects ( Mendelian disorders )
- storage disorder , inborn errors of metabolism
- eg : sickle cell anemia , thalassemia , CF , Von Gierke’s disease

2) Disorder w/ multi factorial ( polygenic) inheritance
- involve both genetic & environmental influences
- eg T1 diabetes , colon cancer , heart disease

3) Chromosomal disorder
- may be numerical or structural abnormalities
- ex : Down syndrome , Klinefelter syndrome

39
Q

Describe the vascular & cellular response during acute inflammation

A

A) Increase in blood vessel calibre & flow

  • due to dilation of small blood vessels resulting in greater blood flow
  • at first there is transient vasoconstriction followed by vasodilation
  • induced by histamine
  • it is the cause of erythema & stasis of blood flow

2) Increase in membrane permeability
- induced by histamine & kinins producing gaps between endothelial cells
- allows plasma protein & leukocytes to enter sites of infection of damage —> exudate formation
- vasodilation leads to increased blood flow . Increased hydrostatic pressure and decreased intravascular osmotic pressure leads to edema
- lymphatics also involved in inflammation

3) Extravasation of leukocytes ( neutrophils)
- neutrophils recruited from the blood into extravascular tissue & activate to perform their functions m recognition & phagocytosis
- multi step process m marginatum , rolling , adhesion & transmigration
- involves cytokines & chemokines which promote directional migration of leukocytes ( produced by macrophages )

40
Q

Describe the formation of cellular exudates & removal of pathogens in detail during acute inflammation

A
  • multi-step process
  • does not occur in arteries because too thick

1) Margination
- leukocytes migrate to the periphery of the blood vessel

2: Rolling
- neutrophils bounce/ roll along endothelial cells
- they are transiently adherent to the cells
- rolling adhesion is due to loose binding b/w selection on the endothelial cells and the carbohydrates of the neutrophil.

3) Adhesion ( pavementing )
- neutrophils become tightly adherent to endothelium —facilitated by ICAM ( endothelial )and integrin ( neutrophil )
- neutrophil can then extravasate through the vessel wall into the surrounding tissue
- ICAM : intercellular adhesion molecule

4) Transmigration
- mediated by PECAM-1 (CD 31 )
- diapedesis / cell crawling from the blood vessel into the extravascular space occurs through intercellular junctions

5) Migration / chemotaxis
- leukocytes after citing circulation , move toward the site of injury
- due to presence of chemoattractants which can be exogenous ( bacterial products ) and endogenous ( cytokines )
- the chemotactic agents binds to 7 transmembrane GPCR on the surface of the leukocytes

6) Leukocytes activation
- bacterium / particles gets coated ( by C3b or IgG ) in order to facilitate its phagocytosis — opsonisation
- phagocytosis
- release of leukocyte products

7) Lysosomal action
- once bacterium is phagocytosed -> degraded by lysozymes containing acid hydrolyses
- lysosomes can also make antimicrobial peptides by combining super oxygen radicals w/ nitric oxides to form peroxynitrite -> cause respiratory burst ( oxidative damage )

41
Q

State the important opsonizers

A
  • IgG , C3bb , IgM
42
Q

State the endogenous & exogenous chemoattractants

A

Chemoattractants : small soluble molecules that bind to receptors on leukocytes & regulates their trafficking

Endogenous
I) Cytokines , particularly those of the chemokine family (IL-8 )
II) Components of the complement system ( C5a)
III) arachidonic acid metabolites ( leukotriene B4 )

Exogenous
I) Bacterial products
II) peptides w/ N-formylmethionine terminal amino acids
III) some lipids

43
Q

In most forms of acute inflammation , ( …….. ) predominate during the first 6-w4 hours and then replaced by ( ………. ) after 24-48 hours

A

In most forms of acute inflammation , ( neutrophils ) predominate during the first 6-w4 hours and then replaced by ( monocytes ) after 24-48 hours

44
Q

In acute inflammation , increased membrane permaebility may be due to :

A

I) Constriction of endothelial cell by histamine & kinins —> produce gaps b/w cells
- generally short-lived

II) Endothelial cell injury due to burns , microbial toxins
-generally long lived

45
Q

Exudates refers to extravascular fluid w/ (…….. ) protein content & contain ( …….. ) . It is a sign of inflammation , caused by increased permaebility of small blood vessel.

Transudate refers to extravascular fluid w/ ( ……. ) protein content & (…………. ) . It is produced as a result of differences in hydrostatic & osmotic pressure across the vessel wall. Not caused by in creased permaebility of blood vessels.

A

Exudates refers to extravascular fluid w/ ( high ) protein content & contain ( contain cellular debris ) . It is a sign of inflammation , caused by increased permaebility of small blood vessel.

Transudate refers to extravascular fluid w/ ( low ) protein content & ( little or no cellular materials ) . It is produced as a result of differences in hydrostatic & osmotic pressure across the vessel wall. Not caused by in creased permaebility of blood vessels.

46
Q

List the cell-derived and plasma-derived mediators of inflammation

A

A) Cell derived :
i) Performed mediators in secretory granules : Histamine & Serotonin
II) Prostaglandin , Leukotrienes , Platelet-activating factor , Reactive oxygen species , Nitric oxide , Cytokines , Neuropeptides

B) Plasma protein derived :
I) Complement activation : C3a , C5a ( anaphylatoxin ) ; C3b ; C5a-9 ( membrane attack complex )
II) Factor XII ( Hageman factor ) activation : Kinin system , Coagulation / fibrinolysis system

47
Q

Describe the role of mediators in different reaction of inflammation

A

I) Vasodilation : Prostaglandins , Nitric oxide , Histamine

II) Increased vascular permaebility : Histamine and serotonin , C3a and C5a , Bradykinin

III) Chemotaxis , leukocytes recruitment and activation : TNF , IL-1 , Chemokines , C3a , C5a

IV) Fever : IL-1 , TNF , Prostaglandins

V) Pain : Prostaglandins , Bradykinin

VI) Tissue damage : Lysosomal enzymes of leukocytes , Reactive oxygen species , Nitric oxide

48
Q

Describe abscesses

A
  • localised collection of pus w/ a central region of necrotic tissue surrounded by neutrophils , congested vessels & fibroblasts
  • caused by seeding of pyogenic bacteria (Staphylococci ) into a tissue , organ or confined space.
  • as time passes , abscesses may be completely walled off & replaced by CT
49
Q

Describe ulcers

A
  • a local defects or excavation of the surface of an organ or tissue that is produced by the sloughing / shedding of inflammed necrotic tissue
  • only occurs when tissue necrosis and resultant inflammation exists on or near a surface
  • commonly occurs in :
    I) mucosa of mouth , stomach ( peptic ulcers ) , intestine , genitourinary tract
    II) skin & subcutaneous tissue of lower extremities ( diabetes ulcer )
50
Q

Describe the sequelae of acute inflammation

A

1) Resolution ( regeneration and repair )
- occurs if the injury is short-lived / limited , minimal tissue damage has occurred and the damaged tissue is able to regenerate
- tissue is repaired to structural & functional normalcy
- process of inflammation must be terminated to prevent bystander destruction of tissues

2) Abscess formation
- occurs when acute inflammation fails to resolve —> extensive tissue destruction occur with formation of a cavity —> inflammation continues to smolder & leads to abscess formation
- ex : in acute bacterial pneumonia , chronic lung abscess is formed

3) Progression to chronic inflammation
- Acute inflammation transitions to chronic inflammation when the inflammation response persists.
- may be due to perseverance of injurious stimuli or interference w/ normal healing process

4) Healing process
- occurs due to :
I)extensive tissue destruction
II) when the inflammatory injury involves tissues that cannot regenerate
III) when there is abundant fibrin exudation — when fibrinous exudate cannot be adequately cleared ( like in pleural, peritoneal , synovial cavities ) -> CT grows into areas of exudates -> converting it into a mass of fibrous tissue ( this process is known as organisation )

51
Q

Explain the beneficial effects of inflammation

A

1) Dilutions of toxins by edema fluid
2) Production of protective antibodies ( via cytokines ) & promotion of immunity

3) Formation of fibrin mesh work
- acts as a scaffold for inflammatory cell migration & limits the spread of the bacteria
- phagocytosis of microbial pathogens can occurs easily , tissue debris can be removed

4) Cell nutrition

52
Q

Explain the harmful effects of inflammation

A

1) Swelling and edema can be detrimental
- example : acute epiglottitis -> constriction of airways

2) Rise in tissue pressure contributes to tissue necrosis
- due to compression of surrounding vessels —> ischemia & necrosis

3) Digestion of adjacent viable tissue
- action of phagocytes if unregulated

4) Severe damaging allergic reaction
- as seen in hypersensitivity reactions

5) Generalized increase in vascular permaebility can leads to shocks
- caused by hypotension -> lack of perfusion to vital organs & tissues —> ischemia —> necrosis
- eg : septic shock , anaphylactic shock

53
Q

Explain the systemic effects of inflammation

A
  • also known as acute phase reactions or systemic inflammation response syndrome ( RDS )
  • mediated by IL-1 , IL-6 and TNF

I) Fever
- endogenous pyrogens ( IL-1 , TNF) and exogenous pyrogens (LPS) stimulate the production of cytokines which then stimulate the synthesis of prostaglandins in the hypothalamus —> sets the temperature set- point at a higher level leading to fever.

II) increase in acute phase proteins

  • proteins produced in the liver , stimulated by IL-6 & IL-1
  • C reactive protein (CRP) , fibrinogen & serum amyloid proteins (SAA)
  • CRP & SAA acts as opsonins

III) Leukocytosis
- leukocytes count climbs to 15k- 20k cells / uL but in some cases may reach 40k - 100k cells /uL ( leukemoid reactions — similar to those seen in leukaemia )
- occurs due to :
I) accelerated release of WBC ( under the influences of TNF & IL-1 ) from the bone marrow post-mitotic reserve pool
II) increase production of WBC from the bone marrow due to increase colony stimulating factors ( CSFs)

54
Q

Describe the mechanism of resolution of acute inflammation

A

I) Leukocytes

  • half life of neutrophils & chemical mediators are short —> undergo apoptosis & ingestion by macrophages
  • macrophages changes character ( into anti-inflammatory M2 macrophages ) & promote repairs as well as release inhibitory cytokines ( IL-10 , TNF-B ) which limits inflammation

II) Growth factors ( FGF ) act on fibroblast — promote repair

III) Lipid mediators —> switch to production of anti-inflammatory lipoxins , resolvins and protectins

55
Q

IL -1 is an ( ……… ) cytokines whereas IL-10 is an (………. ) cytokine

A

IL -1 is an ( inflammatory ) cytokines whereas IL-10 is an ( anti-inflammatory) cytokine

56
Q

Describe some causes of chronic inflammation

A

1) Persistence infections by microbes that are difficult to treat
- ex : Mycobacterium tuberculosis , tryponema pallidum , fungi

2) Prolonged exposure to toxic agents
- agents may be exogenous or endogenous
- ex : inhaled particulate silica —> chronic inflammation of the lungs i.e silicosis ( exogenous ) ; cholesterol crystal -> atherosclerosis ( endogenous )

3) Immune-mediated inflammatory disease
- caused by excessive & inappropriate activation of the immune system
- autoantigens evoke a self-pertuating immune reactions that results in tissue damage & persistent inflammation
- ex: rheumatoid arthritis , SLE , inflammatory bowel disease

4) Disease of unknown aetiology
- ex : inflammatory bowel disease

57
Q

Describe the microscopic features of chronic inflammation

A
  • infiltration w/ mononuclear cells ( macrophages , lymphocytes & plasma cells )
  • tissue destruction largely induced by the products of the inflammatory cells
  • tissue repair , involving angiogenesis & fibrosis
58
Q

Describe the macroscopic appearance of chronic inflammation

A

1) Presence of chronic ulcers
- eg : chronic peptic ulcers of the stomach

2) Presence of chronic abscess cavities
- eg : osteomyelitis, empyema thoracis

3) Thickening of the wall of a hollow viscus ( organ ) by fibrous tissue ( fibrosis )
- eg : Crohn disease —> produce hour- glass contracture of the stomach , chronic cholecystitis

4) Granulomatous inflammation
- eg m chronic fibrocaseous tuberculosis of the leprosy , syphilis , cat- scratch disease

59
Q

Which cytokine is involved in the activation of monocytes to macrophages?

A

Interferon-y ( IFN-y )

60
Q

Explain cellular co-operation in chronic inflammation with the help of a suitable diagram using granuloma formation as an example

A
  • antigen - presenting cells ( DC , macrophage) phagocytosed & process the antigen -> present antigens to T-lymphocytes
  • T - lymphocytes become activated forming helper (CD4+) T lymphocytes
  • CD4+ TH1 cell release cytokines ( TNF , chemokines ) which recruit monocytes to the site of inflammation from blood vessels
  • Monocytes get activated to macrophages ( epithelium cells ) by IFN-y (released by T cells )
  • Activated macrophages in turn stimulates T cells by presenting antigens and via release of cytokines like IL-12
  • Accumulation of chronic inflammatory cells ( lymphocytes , macrophages , fibroblasts ,epitheloid cell , giant cells) —> granuloma formation
61
Q

Explain the roles of macrophages in chronic inflammation

A

2 types :

1) Classically activated macrophages (M1) — microbicidal
2) Alternative activated macrophages ( M2)— tissue repair

I)Phagocytosis & elimination of microbes & dead tissue

II) Secrete mediators of inflammation such as cytokines ( TNF , IL-1 , chemokines ) and eicosanoids

III) acts as APC
- T cells activate macrophages , and macrophages in turn activate more T cells by phagocytosis & presentation of microbial antigen

IV) Initiate process of tissue repair & fibrinosis & angiogenesis
- by releasing TGF-B & FGF —> increase proliferation of fibroblast —> increase deposition of collagen

62
Q

( ………….. ) and ( ………..) induce classical macrophage activation (M1)

Alternative macro activation is induced by cytokines such as (……..) and (……..)

A

( Microbial products like exotoxins , T-cell derived signals ) and ( IFN-y ) induce classical macrophage activation (M1)

Alternative macro activation is induced by cytokines such as ( IL-4 ) and ( IL-13 )

63
Q

Describe granuloma and its types

A

A form of chronic inflammation characterised by accumulation of epithelioid cell surrounded by lymphocytes , plasma cells , fibroblasts , multinucleated giant cell and sometimes associated with central necrosis

Types :
I) Foreign body granulomas
-incited by relatively inert foreign bodies
- absence of T-cell mediated immune response
- eg catgut (sutures ) , talc , fibers

II) Immune granulomas

  • caused by agents that are capable of inducing a persistent T-cell mediated immune response
  • macrophages engulf foreign protein antigen ( microbe or self antigen) , process it and present peptides to antigen specific T lymphocytes , causing their activation.
64
Q

Describe the morphology of granuloma ( gross , histological )

A

Gross :
- granular , cheesy appearance —> caseous necrosis

Histological

  • pink amorphous granular debris enclosed within Granulomatous reaction
  • older Granulomatous may have rim of fibroblast & CT
  • pink amorphous granular debris —> area of necrosis , Granulomatous reactions —> accumulation of activated macrophages ( epitheloid cells ) which have pink granular cytoplasm with in distinct cell boundaries , surrounded by a collar of lymphocytes , plasma cells , fibroblasts and Langhans giant cells
65
Q

List some causes of granulomatous inflammation

A

1) Tuberculosis
- caused by Mycobacterium tuberculosis

2) Syphilis
- Caused by Treponema pallidum

3) Leprosy
- Caused by Mycobacterium leprae

4) Cat scratch disease
- caused by Gram negative bacillus

5) Sacoidosis , Crohn disease
- granulomas that have no areas of necrosis

6) Foreign bodies
- ex : catgut , talcum powder

66
Q

Langhans giant cells are ( …………… ) giants cells with (…………. ) shape arrangement of nuclei which are seen in (…………….) infections

It is formed by the fusion of (………….. ) & have (………… ) amounts of cytoplasm

A

Langhans giant cells are ( multinucleated) giants cells with ( horseshoe ) shape arrangement of nuclei which are seen in (granulomatous ) infections

It is formed by the fusion of (multiple activated macrophages )& have ( large) amounts of cytoplasm

67
Q

Describe healing by primary intention

A
  • ex : healing of wounds made by clean , uninfected surgical incision
  • occurs by 3 processes : inflammation -> proliferation —> maturation

A) Inflammation

  • wounding—> clot formation
  • damaged endothelial cell VEGF —> increased vessel permaebility & edema forms
  • within 24 hours , neutrophils appears at the margins of the incision —> removal of debris & invading the bacteria

Proliferation

  • in 24-48h , epithelial cell move from the wound edge along the cut margins of the dermis , fuse in the midline & close the wound , providing a thin layer of epithelial continuity
  • by 48-96h , neutrophils replaced by macrophages -> promotes angiogenesis & ECM deposition via release of VEGF & TGF- B.
  • by the 5th to 7th day , granulation tissue fill the wound area & neovascularization is maximal

Maturation

  • T3 collagen is eventually replaced by T1 collagen by remodelling by the 2nd week
  • increased accumulation of collagen causes blood vessels to regress
  • leukocytic infiltrate , edema & increased vascularity disappear
  • dermal appendages ( glands , hair ) that were destroyed in the line of incision are permanently lost
  • by end of 1st month , a scar is formed & epidermis is intact
68
Q

Compare healing by primary intention and seconds intention

A

Primary intention

  • surgical incisons
  • smaller wounds
  • no wound contraction
  • less blood clotting
  • less collagen deposition
  • less scar formation
  • less severe w/ less neutrophils and edema

Secondary intention

  • car accidents
  • larger wounds
  • have wound contraction
  • more blood clotting
  • more collagen formation
  • more scar formation
  • more severe with more neutrophils and edema
69
Q

Explain the systemic factors influencing wound healing

A

1) Nutrition
- nutrients like proteins , Vit C and zinc are involved in collagen synthesis , hence deficiency causes impaired healing

2) Circulation
- blood is responsible for bringing nutrients to tissues
- if circulation is impaired example atherosclerosis , varicose veins then , wound healing is delayed

3) Metabolic status
- presence of disease like diabetes Mellitus will cause delayed wound healing as it affects blood circulation

4) Hormones
- glucocorticoid causes weakness of scar tissue due to inhibition of TGF-B production & diminished fibrosis

70
Q

Explain the local factor influencing wound healing

A

1) Infections
- microbial infections can result in persistent tissue injury & inflammation

2) Mechanical factors
- eg : disruption of the wound ( picking , stretching ) —> destroys newly formed granulation tissue —> delays healing & separates the edges of the wound

3) Presence of foreign bodies
- ex : steel , glass , bone , suture , paint -> impairs healing

4) Size , location and type of wound
- wounds in richly vascularised tissue -> heal quickly
- small incisional injuries -: heal faster with less scar formation

71
Q

Explain the complications of wound healing

A

1) Formation of hypertrophic scar / keloid
- due to excessive amount of collagen —> hypertrophic scar
- if scar tissue grows beyond’s the boundaries of the original wound & does not regress —> keloid

2) Wound dehiscence & ulceration
- occurs in inadequate formation of granulation tissue
- eg : rupture of wound after abdominal surgery due to raised abdominal pressure

3) Exuberant granulation
- formation of excessive amounts of granulation tissues ( proud flesh )

4) Wound contraction
- contraction in size of wound is normal in healing process but exaggeration of this process -> contracture
- prone to develop on the palms , soles , anterior aspects of thorax
- seen after serious burns & can compromise movements of joints

72
Q

Describe how a bone fracture is healed

A

1) Formation of hematoma
- bone fracture -> ruptured blood vessels -> formation of blood clots ( hematoma )
- hematoma provides a fibrin mesh which seals off the fracture at the same time creates a framework for the influx of inflammatory cells & ingrowth of fibroblasts & new capillaries
- platelet & migrating IF cells secrete PDGF , FGF , TGF -B which activate osteoprogenitor cells & stimulate osteoblastic & Osteoclastic activity

2) Formation of procallus
- at the end of 1 week , a soft tissue callus forms consisting of osteoclasts & osteoblasts , platelets , IF cells and their products
- the bone is not strong enough to bear weight yet

3) Formation of bony callus
- after approx 2 weeks , the procallus is transformed into bony callus
- the activated osteoprogenitor cells deposit woven bone
- activated mesenchymal cells also differentiate into chondrocytes , forming fibrocartilage & hyaline cartilage which then undergoes endochondral ossification
- fracture ends are bridge & strength of callus increases to the point where controlled weight bearing can be tolerated

4) Bone remodelling
- excess fibrous tissue, cartilages & woven bone and resorbed in areas not subjected to force while the areas subjected to forces are strengthened
- weight-bearing is necessary in this stage in order for proper bone remodelling to occur
- the callus size reduce & the shape & outline of the fractured bone is reestablished as lamellar bone
- healing process with complete process restoration of the medullary cavity @ the end of approx 2 months

73
Q

Describe some local factors influencing fracture healing

A

1) Degree of local trauma / bone loss
- comminuted , displaced fractures are more difficult to heal than simple fracture
- comminuted - fragmented bone , displaced - ends of both bones are not aligned m simple - hairline fracture

2) Area of fracture
- metaphyseal fracture has more blood supply hence heals faster than diaphyseal fracture

3) Degree of immobilisation
- motion at the site can delay healing example too early during procallus or hematoma stage due to breakage of woven bone , cartilage

4) Disruption of vascular supply
- less nutrients & cells to site of fracture

5) Abnormal bone
- example : infections , tumours , irradiated bone are slower to heal

74
Q

Describe the systemic factor influencing fracture healing

A

1) Nutrition
- vitamin & nutrient healing deficiency delay fracture healing
- Vit C need in collagen synthesis

2) Metabolic status / general health
- chronic illness suppress healing
- example diabetes Mellitus , anemia , systemic infection

3) Hormones
- PTH —> increases blood C levels by increasing resorption of bone —>may delay wound healing
- Corticosteroids depress healing
- Growth hormones increase healing

4) Systemic circulation
- obstructed circulation decreased healing
- atherosclerosis

5) Age
- young —: heals faster

75
Q

State some complication of fracture healing

A

1) delayed union or healing
- duration of healing is delayed or bone does not heal at all
- commonly seen in displaced & comminuted fractures

2) Malunion
- bone may become twisted , shortened or bent

3) Pseudoarthrosis / false joint formation
- occurs if nonunion persists —> malformed callus undergoes cystic degeneration & the luminal surface become line by synovial-like cells forming a false joint

Pathology (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions