cell injury lecture transcription

7/31/2019 Cell Injury Lecture Transcription

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BEFORE STARTING THIS BASIC LECTURE SERIES

HERE ARE SOME IMPORTANT POINTERS TO

REMEMBER:1. The learning objectives provided in here are your lifelines in the

Pathology course. It is a must that you understand them and answer

them. The very first question however you must answer is WHATAM I RESPONSIBLE FOR? Do not be put off by thisquestion instead strive to learn and not memorize, diligently adhere tothese learning objectives in preparing for your lectures and these will

guarantee meaningful lectures which will greatly augment your learning

experiences in this course. READ TO LEARN NOT TO PASS YOUR

EXAM. The rule of thumb is THE STUDENT WHO CAN ANSWER

ALL THE OBJECTIVES NEVER FAILS AND WILL BE REWARDED

ACCORDINGLY.

2. You will be given a list of medical terminologies that you must be able todefine and at least give an example to demonstrate your knowledge about

the subject matter. Understanding them is essential and VERY EASY,

any medical dictionary or pathology textbook will define them for you.

3. Make the most of the laboratory sessions especially the basic courses

because this is an effective learning experience. This lecture series will

however demonstrate key concepts through gross and micrographs that

will be provided to enhance your learning and which will reinforce the

unifying principles that lecturers have presented.

MEANINGFUL LEARNINGis a big word. Incorporate and relate new knowledgeacquired to every memorable experiences you have had. HOW ? ! ! ! Knowing that

you are a medical student, has any of your friends or relatives ask you about diseases

in your family, e.g., Ano sa palagay mo ang dahilan ng pagkamatay ni lolo or ni

lola? Sabi ng doctor inatake daw sa puso, paano ba nangyari iyon? Namamana ba

yon? This are simple questions laymen ask but you as a medical student armed at

this point in time with anatomy and physiology must be able to make your relatives or

friends understand the function and malfunction of the heart. If you cannot, GO

BACK TO YOUR TEXTBOOK AND READ TO UNDERSTAND kasi nakakahiya

ka !!! or would you rather stack your comfort room with Robbins and Harrisson

and everytime youre asked questions EXCUSE YOURSELF to go to the bathroom

and read ? ! !.

4. If at this point in time, you think that your learning skills are lacking, askfor help through expert coaching. You are a very talented person and

must not endure the STIGMA OF ACADEMIC FAILUREand it will be

TRAGICfor us to allow you to be in your clinical years poorly equipped

in understanding disease.


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THE QUEST FOR KNOWLEDGE STARTS HERE ! ! !

ANATOMIC PATHOLOGYCOURSE DESCRIPTION:

The subject provides background knowledge on general pathology, cellular/tissue reaction to

injury and inflammation, reparative mechanisms of healing and immunity. It also providesbackground knowledge in the study of relationships between, host, environment and pathogen in

health and disease. The subject offers by demonstration common morphologic changes of cells andtissues in reaction to common pathogens.

CELLULAR INJURY AND ADAPTATION

COURSE OBJECTIVES:

General Instructional Objectives:

1. Review the components of normal cells.2. Familiarize the student with common medical terminologies

related to pathology.

Enabling Objectives:

1. List the features / characteristics common to all cells.

2. Characterize the different cellular components as toultrastructural features and function.

General Instructional Objectives:

3. Enumerate the four (4) aspects of a disease process.

a. Define each

4. Discuss the relationships between these aspectsthat portray different disease entities.

Can it be, that asking questions is teaching? I am

just beginning to see what is behind all your

questions. You lead me on by means of things I

know, point to things that resemble them, andpersuade me that I know things that I had no

knowledge of.

SOCRATES

OF SCIENCE AND OPINION

The former produces knowledge,

the latter produces ignorance. Hippocrates


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General Instructional Objective:

5. Understand the different concepts of cellular injury.


1. Define or describe the following:a. homeostasis

b. steady state

c. atrophyd. hypertrophye. hyperplasiaf. induction of endoplasmic reticulum

2. List the different causes of cell injury/death.a. Exemplify with at least 2 clinical entities to illustrate

the different causes.

3. Enumerate the factors that determine the extent of damageresulting from a given cellular injury.

4. Discuss the four common causes and mechanisms of cell injury.

5. Tabulate the differences between reversible and irreversible injuries.

a. Characterize cellular swellingandfatty change.6. List thefour intracellular systems vulnerable to injury.

7. Define or describe the following:

a. necrosis

i. coagulation necrosis

ii. liquefaction necrosis

iii. fat necrosis

iv. caseous necrosis

v. gangrenous necrosis

b.pyknosis/karyolysis/karyorrhexisc. apoptosis

8. Discuss the basic mechanisms ofintracellular accumulation.9. List the three categories of stockpiled substances.

a. give the common clinical/pathologic settings associatedwith each

General Instructional Objective

6. Understand theprinciples and concepts of cellular adaptation.


1. Describe and exemplify the following cellular adaptations:a. atrophyb. hypertrophyc. hyperplasia

d. metaplasiae. dysplasia


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General Instructional Objective:

7. Understand the other cellular and tissue alterations:


1. Define or describe calcifications.

a. List examples ofdystrophic calcification.b. List examples ofmetastatic calcifications.

2. Describe hyaline change.

MEDICAL TERMINOLOGIES TO LIVE BY:

ANATOMIC PATHOLOGY NEVER READ OVER AN UNFAMILIAR

CLINICAL PATHOLOGY WORD WITHOUT LOOKING UP ITS

SYSTEMIC PATHOLOGY MEANING ! ! !GENERAL PATHOLOGY

PATHOGENForme fruste

DISEASE

FUNCTIONAL DISEASE CRAMMING IS THE WORST THING YOU

DIATHESIS CAN DO, BECAUSE THE MINUTE YOU GET INTO

LESION IT, YOU FORGET IT.RISKPATHOGNOMONIC

PREVALENCE

PROGNOSISAPOPTOSIS

SIGNSYMPTOM

SYNDROMEAPLASIA

ATRESIA

CYTOLYSISCYTOPATHIC

FIBRINOID

INCLUSION BODYGANGRENE

MORPHOLOGY

CLINICAL SIGNIFICANCEDYSTROPHYCALCIFICATION

Now is the best time to read the good stuff !!!

Your textbook not your text messages ! duh!!!


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HAVING THIS MODULE WILL HELP YOU BUT IS NOT A

SUBSTITUTE FOR YOUR TEXTBOOK.

Pathologyis defined as the science of disease or study of disease.Pathos is a Greek word meaning human condition or suffering . In this course, we will

consider every factor that brings about disease. Thus it is of utmost importance to know thebasic aspects of any disease process:

ETIOLOGY : the cause

Remember: Never fall into the trap of simplistic definition that diseases have

a single cause; diseases are always multifactorial

PATHOGENESIS: the sequence of events leading to disease

MORPHOLOGIC CHANGES : anatomic deviation from the normal

CLINICAL SIGNIFICANCE : how the disease has affected the functional capacity of

a cell, tissue, organ-system or the whole individual; is

synonymous with functional derangement

LET US LOOK INTO THE COMMON COLDSEtiology : common cold virus RhinovirusesPathogenesis : you and your classmates have not been having a good nights rest , you

have weakened your immune defenses, you catch an airborne viralinfection lodging in your upper respiratory tract

Morphology : congested and edematous respiratory tract mucosa, congested sinuses

Clinical Significance : stuffy nose, sinus headache, febrile, feeling sick , CANNOTSTUDY YOU FAIL YOUR QUIZ

The lesson of the story : YOU CANNOT LEARN DAY-TO-DAY UNLESS YOU GET

SLEEP MOST NIGHTS. So do not cram ! ! ! Set 2 hours every

day for studies for these will sum up to weeks in the long run !!!

PUT THIS INTO YOUR MIND AND DWELL ON IT ! ! !

WHATEVER HURTS THE CELL HURTS THEINDIVIDUAL !!!

CAUSES OF INJURY:

COMMON ETIOLOGY OF DISEASES

Hypoxia Chemicals and drugs Physical Agents

Microbiologic Agents Immunologic reactions Genetic Defects

Nutritional Imbalances

Aging


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INTRACELLULAR SYSTEMS VULNERABLE TO INJURY 1. Integrity of cell membranes 2. Aerobic Respiration 3. Synthesis of Enzymes4. Integrity of the Genetic Apparatus of the cell

PRINCIPLES AND CONCEPTS OF CELLULAR ADAPTATION

Homeostasis : equilibrium; steady state Adaptation : new but altered steady state achieved to preserve cell viability 1. Atrophy : decrease in size

CAUSES :

a. Decreased workload

b. Loss of innervation c. Diminished blood supply d. Inadequate nutrition

e. Loss of endocrine stimulation f. Aging

o

2. Hypertrophy : increase in sizeCAUSES:1. Physiologic

a. Hormonal b. Compensatory 2. Pathologic a. Excessive Hormonal stimulation b. Viral-induced

o

3. Hyperplasia : increase in the numberCAUSES :

1. Physiologic

a. Hormonal

b. Compensatory

2. Pathologica. Excessive Hormonal stimulation

b. Viral-induced

4. Metaplasia : replace adult cell by another adult cell typeCAUSES :

- Persistent Irritation

- Infection


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- Malnutrition

5. DYSPLASIA : deranged development- Proliferation and atypical cytologic alterations

- change in size, shape and organization

not an adaptive mechanism but a change for the WORSE

o

ATROPHYThe muscle cell pointed

is characteristically

smaller as compared to

the other cells present.

The cell has decreased in

size.

The enlargement of the thyroid

gland is due to increase in the

number of thyroid cells due to

effects of thyroid stimulatinghormone TSH to increase

production of thyroid hormone.

This is also exemplified by uterusin pregnancy as a compensatory

increase in number in preparation

for conception in response tohormonal changes.


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NECROSIS- sum of all the morphologic changes that follow after cell death, classified as:

liquefaction necrosiscoagulative necrosis

enzymatic fat necrosis

caseous necrosis

gangrenous necrosis

LIQUEFACTION NECROSIS

Results from action of powerful hydrolytic enzymes, intrinsic or extrinsic

- best exemplified by BRAIN INFARCTION

brought about by ischemic destruction of brain tissue

- common pus , abscess, SUPPURATION due to bacterial action

COAGULATIVE NECROSISResults from total occlusion of supplying vessels especially in solid organs resulting to:

- conversion of the cell to acidophilic tombstone

Dissolution of the brain tissue is

evidenced by replacement byhistiocytes, e.g., tissue macrophages

Infarcted area

When muscle is exposed to

stresses, e.g., weightlifting, orhypertension for heart muscle,

the cells increase in size to

accommodate and adapt to thestress. Ultrastructurally, the

component organelles becomenumerous and increase in sizewith corresponding increase

in weight.

Compensatory increase in

size also occur in a pregnantuterus.


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- loss of nucleus but with cell architecture preserved - protein denaturation ( precipitation)

- exemplified by MYOCARDIAL INFARCTION

WHAT TO LOOK FOR ? ! ! !LOOK AT THE CELL AND NOTICE THE NUCLEUS:

In liquefaction necrosis the cell is dissolved the whole cell is gone.

In coagulative necrosis, the cell outline is retained but the nucleus is gone ! ! !

ENZYMATIC FAT NECROSISDestruction of fat resulting from abnormal release of enzymes especially LIPASES

- exemplified by ACUTE PANCREATITIS - Saponification : action of lipase on fat results in dissolution together with hydroxyl ions (-OH) will produce soap with addition of calcium

will result in formation of chalky material

Infarcted AreaDead cell , no nucleus


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ACUTE PANCREATITIS

CASEATION NECROSIS

Combination of coagulative and

liquefactive necrosis

- exemplified by TUBERCULOSIS

- cheesy appearance, creamy,

white and crumbly


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GANGRENOUS NECROSISCombination of liquefaction and coagulative necrosis

- 2 types : DRY and WET > depends on predominance of necrosis - gangrene of the foot due DIABETES is classified as DRY

- gangrene of loose organs ,e.g. appendix is classified as WET

The medical model is quite simple learn where the bits are, findout how they work, observe the sort of things that can go wrong and

then note carefully what sort of symptoms and signs occur in patientswho turn out to have the pathology already studied. Then you canintervene by repairing anatomy, physiology or removing / suppressingthe pathology.

EXAMINE THESE TWO PICTURES taken from liver samples

Caseation necrosis

Normal lung


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A Note that the cells are loaded withthese clear vacuoles imparting a signet-

ring appearance of cells brought about

by fatty infiltration.

FATTY LIVER

B This micrograph show enlargementof hepatocytes displayed as bloating due

to influx of water into the cell. The

cells are swollen such that thecharacteristic hexagonal shape of

hepatocytes is lost.

CELLULAR SWELLING

These show the two light

microscopic patterns of

reversible injuries most

commonly encountered.

A

B


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d. Failure of cytochromesAll of these boils down to the simple concept of AEROBIC RESPIRATION, remember ATP

production or oxidative phosphorylation, e.g., Krebs Cycle, thus in pathology we talk of hypoxia as

failure to carry on sufficient aerobic respirationand this lead to a shift to anaerobic respirationand for some reason the cytoplasmic membrane loses its ability to keep sodium and water from

diffusing into the cell ( Na/K pump requires ATP) thus the first reversible injury noticeable is

CELLULAR SWELLING.

MALNUTRITION : poor nutrition affects everybody in a peculiar way as it affects the

cell. What do you feel when youre hungry ? headache, irritability as well as confusion,

WHY?!!! because the brain cells need glucose as much as oxygen to function.The cells without food waste away and die NOT LIKE YOUR JEANS THAT NEVER DIES

BUT JUST FADE AWAY !!!

MICROBIOLOGIC AGENTS : the infectious agents causes cell injury in a variety of

ways ranging from outright destruction to subtle commensalisms

PHYSICO-CHEMICAL AGENTS : too much of the good thing is damaging. Theinterest nowadays is shifting to FREE RADICAL FORMATION , e.g., oxygen radicals,

and networkers as well as pyramidal schemers are zeroing on this with their products, likealmost everything you see and hear in the TV, movies and mags, the dreaded rivals of

Robbins. Thus when free radicals are generated the notable results are:

a. Oxidation of unsaturated fatty acids

b. Cross-linking of sulfhydryl groups of protein

c. Genetic mutations

We however dispose of free radicals by:

a. antioxidants b. detoxification by superoxide dismutase

c. catalasesd. gluthathione peroxidasesChemicals on the other hand affect the more vulnerable parts of the cell, remember the vulnerable

systems (4). Acids and alkali hydrolyze membranes. Mercury tie up sulfhydryl groups while

formalin crosslinks amino groups on proteins and nucleic acids. The classic poisons likewise attackthese systems, cyanide acts on the P-450 cytochrome system inhibiting oxidative phosphorylation.

THIS WILL GO ON AND ON AND ON UNLESS I STOP AT THIS POINT. YOU

HOWEVER SHOULD START READING AND MAY I SUGGEST THAT INSTEAD OF

The law of nature is adapt or die. Theadaptive phenomena is actually

considered plainly as up regulation of

surface receptors. Ooops !!! too big aphrase for you. Let us leave this to the

physiologist and proceed to common

causes of cellular injury and adaptation.

HYPOXIA : too little oxygen is stillthe most common cause of cellular injury

and death and brought about by:

a. Ischemiab. Hypoxemia

c. Hemoglobin problems


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SENDING TEXT JOKES WHY NOT SEND PATHOLOGY QUESTIONS OR TRIVIA FOR

THAT MATTER TO MAKE THINGS INTERESTING !!! Start with this histology trivia to keepthe ball rolling. What is the lining epithelium of the normal introitus? (thats the vagina

dummy !!!) ans: stratified squamous epithelium. epithelium of just married girl ? ans:SATISFIED Squamous epithelium .Epithelium of a widow or a girl who has just lost herboyfriend ? ans: PSEUDOSATISFIED Squamous epithelium

LET US NOW HAVE A VIABLE DISCOURSE ON INTRACELLULARACCUMULATIONS. They say that PICTURES speak a thousand words. This will

only work for you if you SCRUTINIZE and ask yourself a thousand questions.

THUS YOU LEARN BY THINKING AND DOING, NOT JUST LOOKING

especially during examinations at your SEATMATES ANSWERS ! ! !

INTRACELLULAR

ACCUMULATIONS

- increased production withnormal metabolism

- lack of enzymes for

endogenous by-products

of metabolism

- exogenous substance not

metabolized because of

absent enzyme

LIPOFUSCHIN PIGMENTS- insoluble pigment also

known as lipochrome or wear and tear pigmentderived from lipidperoxidation of polyunsaturated lipids

- telltale sign of free radicalinjury

- appears as yellow-brownfinely granularperinuclear-intracytoplasmic granule

- seen in brown atrophy ofheart


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GAUCHERS DISEASE ( glucocerebroside)

- glycolipid storage disease due to lack of

glucocerebrosidase leading to accumulation in

phagocytic cells of glucocerebroside a by-

product of catabolism of cell membranes ofsenescent wbc/rbc called the

GAUCHER CELLS

- affects the RES, subtypes with neuronaldegeneration

HEMOSIDEROSIS hemosiderin (Prussian blue)- hemosiderin is hemoglobin-derived, granular

crystalline pigment, golden-brown- hemosiderin-pigments represent aggregates of

ferritin micelles- excesses of iron cause hemosiderin to

accumulate within cells as a local or systemic

derangement

JAUNDICE

icterizia ; bile pigment

accumulation

- yellow discoloration of tissues,e.g., sclera/skin

- Bilirubin is the normal

major pigment found in

bile, derived from

hemoglobin but without

iron

- When excessiveaccumulation of bile

appears in the liver or

sometimes kidneys, they

occur as bile lakes


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ANTHRACOSIS

- Black carbon particles or coal dust

- a ubiquitous exogenous pigment asan air pollutant usually lodge in

intraalveolar spaces and ingested by

macrophages and deposited in thehilar lymphatics and lymph nodes

- coal miners lungs , pneumoconiosis

these particles cause a fibroblasticreaction which sometimes lead to

emphysematous changes

TATTOOING

- injection of colored substances

subcutaneously is another exogenouspigment deposited .

CALCIFICATIONS

There are 2 types of calcifications,

dystrophic and metastatic, the

former wherein calcium isdeposited on dead tissues and the

latter when calcium is deposited on

living or viable tissues which

usually occur in

HYPERCALCEMIC STATES.

So as not to forget, I adviseyou to know both but remember only

Dystrophic calcification occurs onDead tissues.

Atheroscleroticartery

Anthracotic deposits


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HYALINE CHANGE: an alteration within cells or in the extracellular space

which gives a homogenous, glassy pink appearancein routine H&E which does not represent a specific

pattern of accumulation

Chronic Cervicitis with Squamous metaplasia, the

columnar mucin-secreting cells are replaced by stratified

squamous epithelium which is a protective mucosa

Dysplastic epithelium on the right, seen as

hyperchromasia and disorganized maturation of cells.

In America today, the practices of medicine and law have so interfered with the

dying process that death has become a perversion of the natural process.Crit.Care Clin.9:613,1993


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NOW IS THE TIME TO TEST THE KNOWLEDGE YOU HAVEACQUIREDGiven the following questions, choose the best answer to the bestof your ability. Here the most frequently asked question on thistopic as your review.POST-TEST:

1. The best gauge that determines myocardial hypertrophy: (absolute criterion)a. increased left ventricular wall thicknessb. increase in size of individual myocardial fiberc. weight of the heartd. increased cardio-thoracic ration in Chest X-ray

2. The presence of lipofuschin granules intracytoplasmically implies:a. the cell has an intrinsic defect in enzyme system which metabolizes

the substanceb. the cells production of the pigment has exceeded its capacity to

metabolize itc. this extrinsic pigment cannot be metabolized because of absence of

enzymed. the cell has lost its capacity to metabolize the pigment because of

degenerative processes3. Metaplasia is best characterized as:

a. transformation of an adult cell type to another cell typeb. an irreversible process where epithelia are changed by another cell

typec. protective adaptive change exemplified by chronically inflamed

mucosad. all of the above

4. Type of cellular adaptation where there is marked increase in the number ofautophagosomes accompanied by decrease in the number of mitochondria,myofilaments, and endoplasmic reticulum:

a. hypertrophy c. hyperplasiab. atrophy d. metaplasia

5. The most common cause of hypoxic injury is;a. ischemiab. depletion of oxygen-carrying capacity of blood

c. poisoning of the oxidative enzymes within the cellsd. free radical formation

6. The first point of attack of hypoxia or hypoxic injury in the cell is:a. cells aerobic respiration c. synthesis of enzymesb. the cell membrane d. genetic apparatus

7. The sum of all morphologic changes following cell death:a. necrosis c. autolysisb. heterolysis d. autophagy

8. Type of necrosis where in the cell outline and tissue architecture arepreserved:

a. liquefaction necrosis c. caseation necrosis


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b. coagulation necrosis d. enzymatic fat necrosis9. Presence of hemosiderin-laden macrophages is pathognomonic of:

a. degenerative changeb. absence of enzymes to metabolize the pigmentc. previous hemorrhaged. deposition of calcium on dead cells

10. Stony hard white nodule in a tuberculous focus is :

a. caseous necrosis with calcium depositionb. metastatic calcificationc. dystrophic calcificationd. A and C

cell injury lecture transcription

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