You are on page 1of 19

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 WHAT AM I RESPONSIBLE FOR? Do not be put off by this question instead strive to learn and not memorize, diligently adhere to these 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 to define 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 LEARNING is a big word. Incorporate and relate new knowledge acquired 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, ask for help through expert coaching. You are a very talented person and must not endure the STIGMA OF ACADEMIC FAILURE and it will be TRAGIC for us to allow you to be in your clinical years poorly equipped in understanding disease.

THE QUEST FOR KNOWLEDGE STARTS HERE ! ! !


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, and persuade me that I know things that I had no knowledge of. SOCRATES

ANATOMIC PATHOLOGY
COURSE DESCRIPTION: The subject provides background knowledge on general pathology, cellular/tissue reaction to injury and inflammation, reparative mechanisms of healing and immunity. It also provides background 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 and tissues in reaction to common pathogens.

CELLULAR INJURY AND ADAPTATION COURSE OBJECTIVES:


General Instructional Objectives: OF SCIENCE AND OPINION

The former produces knowledge, the latter produces ignorance. Hippocrates

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 to ultrastructural 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 aspects that portray different disease entities.

General Instructional Objective: 5. Understand the different concepts of cellular injury. Enabling Objectives: 1. Define or describe the following: a. homeostasis b. steady state c. atrophy d. hypertrophy e. hyperplasia f. 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 damage resulting 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 swelling and fatty change. 6. List the four 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/karyorrhexis c. apoptosis 8. Discuss the basic mechanisms of intracellular accumulation. 9. List the three categories of stockpiled substances. a. give the common clinical/pathologic settings associated with each General Instructional Objective 6. Understand the principles and concepts of cellular adaptation. Enabling Objectives: 1. Describe and exemplify the following cellular adaptations: a. atrophy b. hypertrophy c. hyperplasia d. metaplasia e. dysplasia

General Instructional Objective: 7. Understand the other cellular and tissue alterations: Enabling Objectives: 1. Define or describe calcifications. a. List examples of dystrophic calcification. b. List examples of metastatic calcifications. 2. Describe hyaline change. MEDICAL TERMINOLOGIES TO LIVE BY: ANATOMIC PATHOLOGY CLINICAL PATHOLOGY SYSTEMIC PATHOLOGY GENERAL PATHOLOGY PATHOGEN Forme fruste DISEASE FUNCTIONAL DISEASE DIATHESIS LESION RISK PATHOGNOMONIC PREVALENCE PROGNOSIS APOPTOSIS SIGN SYMPTOM SYNDROME APLASIA ATRESIA CYTOLYSIS CYTOPATHIC FIBRINOID INCLUSION BODY GANGRENE MORPHOLOGY CLINICAL SIGNIFICANCE DYSTROPHY CALCIFICATION

NEVER READ OVER AN UNFAMILIAR WORD WITHOUT LOOKING UP ITS MEANING ! ! !

CRAMMING IS THE WORST THING YOU CAN DO, BECAUSE THE MINUTE YOU GET INTO IT, YOU FORGET IT.

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

Your textbook not your text messages ! duh!!!

HAVING THIS MODULE WILL HELP YOU BUT IS NOT A SUBSTITUTE FOR YOUR TEXTBOOK.
Pathology is 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 the basic 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 COLDS Etiology : common cold virus Rhinoviruses Pathogenesis : you and your classmates have not been having a good nights rest , you have weakened your immune defenses, you catch an airborne viral infection lodging in your upper respiratory tract Morphology : congested and edematous respiratory tract mucosa, congested sinuses Clinical Significance : stuffy nose, sinus headache, febrile, feeling sick , CANNOT STUDY 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 THE INDIVIDUAL !!!


CAUSES OF INJURY: COMMON ETIOLOGY OF DISEASES
Hypoxia Chemicals and drugs Physical Agents Microbiologic Agents Immunologic reactions Genetic Defects Nutritional Imbalances Aging

INTRACELLULAR SYSTEMS VULNERABLE TO INJURY 1. Integrity of cell membranes 2. Aerobic Respiration 3. Synthesis of Enzymes 4. 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 size CAUSES: 1. Physiologic a. Hormonal b. Compensatory 2. Pathologic a. Excessive Hormonal stimulation b. Viral-induced

o
3. Hyperplasia : increase in the number CAUSES : 1. Physiologic a. Hormonal b. Compensatory 2. Pathologic a. Excessive Hormonal stimulation b. Viral-induced

4. Metaplasia : replace adult cell by another adult cell type CAUSES : - Persistent Irritation - Infection

- 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

ATROPHY
The 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 stimulating hormone TSH to increase production of thyroid hormone. This is also exemplified by uterus in pregnancy as a compensatory increase in number in preparation for conception in response to hormonal changes.

When muscle is exposed to stresses, e.g., weightlifting, or hypertension for heart muscle, the cells increase in size to accommodate and adapt to the stress. Ultrastructurally, the component organelles become numerous and increase in size with corresponding increase in weight. Compensatory increase in size also occur in a pregnant uterus.

NECROSIS
- sum of all the morphologic changes that follow after cell death, classified as: liquefaction necrosis coagulative 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 Dissolution of the brain tissue is evidenced by replacement by histiocytes, e.g., tissue macrophages

Infarcted area

COAGULATIVE NECROSIS
Results from total occlusion of supplying vessels especially in solid organs resulting to: - conversion of the cell to acidophilic tombstone

- 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 ! ! !

Infarcted Area Dead cell , no nucleus

ENZYMATIC FAT NECROSIS


Destruction 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

ACUTE PANCREATITIS CASEATION NECROSIS


Combination of coagulative and liquefactive necrosis - exemplified by TUBERCULOSIS - cheesy appearance, creamy, white and crumbly

Caseation necrosis

Normal lung

GANGRENOUS NECROSIS
Combination 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, find out how they work, observe the sort of things that can go wrong and then note carefully what sort of symptoms and signs occur in patients who turn out to have the pathology already studied. Then you can intervene by repairing anatomy, physiology or removing / suppressing the pathology.

EXAMINE THESE TWO PICTURES taken from liver samples

A Note that the cells are loaded with


these clear vacuoles imparting a signetring appearance of cells brought about by fatty infiltration.

FATTY LIVER

B This micrograph show enlargement


of hepatocytes displayed as bloating due to influx of water into the cell. The cells are swollen such that the characteristic hexagonal shape of hepatocytes is lost.

CELLULAR SWELLING
These show the two light microscopic patterns of reversible injuries most commonly encountered.

The law of nature is adapt or die. The adaptive phenomena is actually considered plainly as up regulation of surface receptors. Ooops !!! too big a phrase for you. Let us leave this to the physiologist and proceed to common causes of cellular injury and adaptation. HYPOXIA : too little oxygen is still the most common cause of cellular injury and death and brought about by: a. Ischemia b. Hypoxemia c. Hemoglobin problems

d. Failure of cytochromes All 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 respiration and this lead to a shift to anaerobic respiration and 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. The interest 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, like almost 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. catalases d. gluthathione peroxidases Chemicals 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 attack these 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

SENDING TEXT JOKES WHY NOT SEND PATHOLOGY QUESTIONS OR TRIVIA FOR THAT MATTER TO MAKE THINGS INTERESTING !!! Start with this histology trivia to keep the 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 her boyfriend ? ans: PSEUDOSATISFIED Squamous epithelium

LET US NOW HAVE A VIABLE DISCOURSE ON INTRACELLULAR ACCUMULATIONS. 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 with normal 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 pigment derived from lipid peroxidation of polyunsaturated lipids telltale sign of free radical injury appears as yellow-brown finely granular perinuclearintracytoplasmic granule seen in brown atrophy of heart

GAUCHERS DISEASE ( glucocerebroside) - glycolipid storage disease due to lack of glucocerebrosidase leading to accumulation in phagocytic cells of glucocerebroside a byproduct of catabolism of cell membranes of senescent wbc/rbc called the GAUCHER CELLS - affects the RES, subtypes with neuronal degeneration 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 excessive accumulation of bile appears in the liver or sometimes kidneys, they occur as bile lakes

ANTHRACOSIS - Black carbon particles or coal dust - a ubiquitous exogenous pigment as an air pollutant usually lodge in intraalveolar spaces and ingested by macrophages and deposited in the hilar lymphatics and lymph nodes - coal miners lungs , pneumoconiosis these particles cause a fibroblastic reaction which sometimes lead to emphysematous changes Anthracotic deposits TATTOOING - injection of colored substances subcutaneously is another exogenous pigment deposited .

Atherosclerotic artery

CALCIFICATIONS There are 2 types of calcifications, dystrophic and metastatic, the former wherein calcium is deposited 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 advise you to know both but remember only Dystrophic calcification occurs on Dead tissues.

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.

HYALINE CHANGE: an alteration within cells or in the extracellular space which gives a homogenous, glassy pink appearance in routine H&E which does not represent a specific pattern of accumulation

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

NOW IS THE TIME TO TEST THE KNOWLEDGE YOU HAVE ACQUIRED Given the following questions, choose the best answer to the best of your ability. Here the most frequently asked question on this topic as your review. POST-TEST:
1. The best gauge that determines myocardial hypertrophy: (absolute criterion) a. increased left ventricular wall thickness b. increase in size of individual myocardial fiber c. weight of the heart d. 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 substance b. the cells production of the pigment has exceeded its capacity to metabolize it c. this extrinsic pigment cannot be metabolized because of absence of enzyme d. the cell has lost its capacity to metabolize the pigment because of degenerative processes 3. Metaplasia is best characterized as: a. transformation of an adult cell type to another cell type b. an irreversible process where epithelia are changed by another cell type c. protective adaptive change exemplified by chronically inflamed mucosa d. all of the above 4. Type of cellular adaptation where there is marked increase in the number of autophagosomes accompanied by decrease in the number of mitochondria, myofilaments, and endoplasmic reticulum: a. hypertrophy c. hyperplasia b. atrophy d. metaplasia 5. The most common cause of hypoxic injury is; a. ischemia b. depletion of oxygen-carrying capacity of blood c. poisoning of the oxidative enzymes within the cells d. 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 enzymes b. the cell membrane d. genetic apparatus 7. The sum of all morphologic changes following cell death: a. necrosis c. autolysis b. heterolysis d. autophagy 8. Type of necrosis where in the cell outline and tissue architecture are preserved: a. liquefaction necrosis c. caseation necrosis

b. coagulation necrosis d. enzymatic fat necrosis 9. Presence of hemosiderin-laden macrophages is pathognomonic of: a. degenerative change b. absence of enzymes to metabolize the pigment c. previous hemorrhage d. deposition of calcium on dead cells 10. Stony hard white nodule in a tuberculous focus is : a. caseous necrosis with calcium deposition b. metastatic calcification c. dystrophic calcification d. A and C