General & Systemic Pathology Concepts_ a Global Overview

General & Systemic Pathology Concepts “A broad-brush introduction to select core concepts and disorders.”

Prepared and presented by Marc Imhotep Cray, Cray, M.D.

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Introduction to Pathology Cell & Tissue Injury and Inflammation Neoplasia Cardiovascular System Respiratory System Gastrointestinal System Renal System Nervous System System Musculoskeletal System Endocrine System

Introduction to Pathology

General pathology is the study of mechanisms of disease, with emphasis on etiology and pathogenesis. Systematic pathology is the study of diseases as they occur  Systematic within particular organ systems it involves:  Etiology  Pathogenesis  Epidemiology  Macro and microscopic appearance  Specific diagnostic features features  Natural history and  Sequelae  Clinical pathology is often referred to as laboratory medicine and includes a number of diagnostic disciplines. 

Pathology provides the  Pathology       

basis for understanding: understanding: The mechanisms of disease The classification of diseases The diagnosis of diseases The basis of treatment treatment Monitoring the progress of disease Determining prognosis Understanding complications



SNOMED-standard classification of disease-considers disease-considers following aspects:  Topography  Morphology  Etiology  Function  Disease  Procedure  Occupation

Gross pathology – macroscopic investigation and observation of disease Light microscopy – thin section of wax or plastic permeated tissues, snapfrozen frozen tissues tissue s Histochemistry – microscopy of treated tissue sections (to distinguish cell components) Immunohistochemistry and immunofluorescence – tagged antibodies (monoclonal better) Electron microscopy Biochemical techniques – e.g. fluid and electrolyte balance, serum enzymes Cell cultures – also allowing cytogenetic analysis microscopy, culturing and identification i dentification Medical microbiology – direct microscopy, Molecular pathology – in situ hybridization (specific genes/mRNA), polymerase chain reaction (PCR)

Cell & Tissue Injury and Inflammation



Cellular and tissue growth is a normal component of normal physiology



Complex intraintra- and intercellular intercellular signaling mechanisms control rate and extent of growth



Many disease processes are characterized characterized by alterations in rate rate and control of cellular and tissue turnover



Defects in these normal control mechanisms may lead to disease states such as neoplasia

(2) 

There are several ways ways in which constituents of body can alter in size in association with a normal physiological mechanism or as part of a disease process  Cells and tissues may increase in size via o Hyperplasia= usually results from increased physiologic demands or hormonal stimulation or o Hypertrophy= in response to increased physiologic or pathophysiologic demands  A decrease in size occurs via atrophy= causes (1) disuse (2) denervation(3) ischemia (4) nutrient starvation (5) interruption of endocrine signals (6) & persistent cell injury

(3) 

differentiated (i.e. mature) Metaplasia= is process whereby differentiated cells change from o

o

cigarette smoke Examples: Chronic irritation of bronchial mucosa by cigarette leads to conversion of ciliated columnar epithelium to stratified squamous epithelium Vitamin A is necessary to maintain epithelia •  Related: Ethiopian National Vitamin A Deficiency Survey Report, 2008. Barrett’s esophagus Specialized intestinal metaplasia=replacement of nonkeratinized stratified squamous epithelium w intestinal epithelium (nonciliated columnar w goblet cells in distal esophagus Due to chronic reflux esophagitis (GERD) • • Associated w risk of esophageal adenocarcinoma

(4) 

Cells and tissues may be damaged by a range of insults:      

physical (trauma and extremes of heat) chemical (e.g. acid) neoplastic (e.g. cancers infiltrating adjacent tissue) infective (e.g. bacterial pneumonia) immune (e.g. autoimmune diseases rheumatoid arthritis) iatrogenic (e.g. drugs causing gastric ulceration)

(1) Definition= A local response to infection or injury tissue and its  Inflammation is a complex reaction of a tissue microcirculation to a pathogenic insult characterized by generation of inflammatory mediators and movement of fluid & leukocytes leukocytes from blood into into extravascular extravascular tissues 



It is a major component of response to cellular cellular and tissue injury Evolution of Inflammation  Engulfment/entrapment  Neutralization of irritant  Elimination of injurious agent

(2) 

Inflammati Inflammation on Characte Characteriz rized ed by o increased blood flow (redness and warmth: rubor and calor) o swelling ( tumor) and o pain (dolor) within affected area o systemic effects including malaise and pyrexia

(3) Is

fundamentally fundamentally a protective/de protective/defensiv fensive e response

Persists until

inciting stimulus is removed & mediators are dissipated or inhibited

Can

be potentially harmful: alle rgy)  Anaphylactic shock (peanut allergy)  Systemic inflammatory response syndrome (SIRS)

Is

closely intertwined with repair

Therapeutic

strategies target critical control points in inflammatory pathways

(4)

(5) Vascular

changes:  Vasodilation and increased blood flow  Increased vascular permeability

Cellular events:

transmigration  Leucocyte transmigration  Phagocytosis Chemical mediators

(acute & chronic)



Acute inflammation occurs during early phase of a reaction to cellular/tissue damage 



It is characterized characterized histologically by presence of acute inflammatory cells (neutrophils) within affected tissue

Acute inflammation may resolve if underlying stimulus is removed, or  it may progress to chronic inflammation

cont’d. 

Acute inflammation occurs through release of inflammatory mediators from damaged tissues and other cells 

This leads to a combination of increased vascular permeability and chemotaxis: attraction of inflammatory cells to area secondary to release of chemicals from site of inflammation

(6) 

Redness (rubor )



Swelling (tumor )



Heat (calor )



Pain (dolor )



Loss of function ( functio laesa)

(fifth cardinal sign added by Virchow)



Patient with a Methicillin-resistant Staphylococcus Staphylococcus aureus wound infection, and classic signs of inflammation

Rubin R and S trayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations



X-ray X-ray of previous patient showing non-union non -union of fracture  Holes are from orthopedic screws screws

Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations



Bone scan of same patient, showing uptake uptake in area of active inflammation


 Leukocytes

(WBCs) are major cellular participants in inflammation and include  Neutrophils  T and B lymphocytes  Monocytes-macrophages  Eosinophils  Mast cells and basophils  Each cell type has specific functions but they overlap and change as inflammation progresses 

Inflammatory cells and resident tissue cells interact with each other in a continuous response during inflammation

(1) Neutrophil

Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th Ed. Baltimore: LLW, 2012.

(2) Endothelial cell


(3) Monocyte/macrophage


(4)


(5)

(6)

cont’d. 

Densely packed (PMNs) with multilobed nuclei (arrows)

Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic

cont’d.

1. Vasodilation/ Vasodilation/ increased blood flow 2. Deposition of fibrin and other plasma proteins (exudate) 3. Transmigration and accumulation of neutrophils

cont’d. 

Vasodilation



Slowing of circulation circulation



Stasis and margination



PMNs at margin of a vessel in acutely inflamed tissue




Chronic inflammation may occur de novo or develop as a sequel to acute inflammation  especially if source of cellular/tissue damage persists persists



It is characterized histologically by presence of chronic inflammatory cells: lymphocytes, plasma cells and macrophages

(2) 

Granulomatous inflammation is a special form of chronic inflammation characterized histologically by presence of granulomas  localized collections of macrophages macrophages  Multinucleate giant cells may also be present



Causes of granulomatous inflammation include  tuberculosis  fungal infections  tissue reactions to foreign material and Crohn’s disease  specific diseases such as sarcoidosis and Crohn’s

(3) 

Lymphocytes Lymphocytes (doubleheaded arrow), plasma cells (arrows) and a few macrophages (arrowheads) are present


Several definitions help in understanding of consequences of inflammation: ■ Edema is accumulation of fluid in extravascular space and interstitial tissues ■ An effusion is excess fluid in body cavities (e.g., peritoneum or pleura) ■ A transudate is edema fluid with a low protein content (specific gravity <1.015) ■ An exudate is edema fluid with a high protein conc. (specific gravity >1.015),  frequently contains inflammatory cells 

Exudates are seen early in acute inflammation and are produced by mild injuries, such as sunburn or traumatic blisters

(2) A serous exudate, or effusion, is characterized by absence of a prominent cellular response and has a yellow, yellow, straw-like color c olor ■

Serosanguineous refers to a serous exudate, or effusion, that contains red blood cells and has a reddish tinge ■

(3) A fibrinous exudate has large amounts of fibrin due to activation of coagulation system system

■

o

When a fibrinous exudate occurs on a serosal surface, such as pleura “fibrinous pleuritis” or “ fibrinous or pericardium, it is termed “fibrinous pericarditis”

A purulent exudate or effusion contains prominent cellular components ■

o

Purulent exudates and effusions are often associated with pathologic conditions, conditions, such as pyogenic bacterial infections, infections, in which polymorphonuclear neutrophils ( PMNs) predominate

In suppurative inflammation, a purulent exudate is with significant liquefactive necrosis  it is equivalent of pus

■


Margination, rolling,

activation activation and adhesion Transmigration (diapedesis) Migration

toward site of injury along a chemokine gradient

Animation

 Tissue injury stimulates production

of inflammatory mediators in plasma & release into circulation  Additional factors are generated by

tissue cells & inflammatory cells  Vasoactive and

chemotactic mediators promote edema and recruit inflammatory cells to site of injury

Rubin R and Strayer DS Eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine, 6th Ed. Baltimore: Lippincott Williams & Wilkins, 2012

 Chemicals that are released from damaged tissues

and inflammatory cells orchestrates inflammatory process 

prostaglandins, leukotrienes & TNF- α e.g. histamine, prostaglandins,

 Protein cascades

originating within plasma are also important in regulating response to tissue injury 

e.g. coagulation, fibrinolytic, complement and kinin cascades



Resolution of inflammation is associated with organization organization of inflammatory reaction:  granulation tissue formation and  myofibroblast proliferation followed by by 

A variable degree of collagen deposition (fibrous scarring) o

Collagen deposition more pronounced if inflammatory process has been prolonged



Tissue injury is usually followed by hemostasis= inflammatory response tissue restructuring w a variable degree of scarring



Factors impairing healing include:  old age  poor nutritional state  excessive tissue damage fragments after a  poor apposition of wound edges (or bony fragments fracture)  presence of foreign material  poor blood supply  infection

1.Tissue 1.Tissue injury results in immediate and prolonged vascular changes. Chemical mediators and damaged tissue cells stimulate vasodilation and vascular injury leading to  2. leakage of fluid into tissues (edema) 3. Platelets are activated to initiate clot formation and hemostasis and increase vascular permeability via histamine release 4. Vascular endothelial cells contribute to clot formation, anchor circulating neutrophils via upregulated adhesion molecules and retract to allow increased vascular permeability to plasma and inflammatory cells at same time 5. microbes (red rods) initiate activation of the complement cascade, which, along with soluble mediators from macrophages, 6. recruits neutrophils to site of tissue injury. 7. Phagocytosis (See next sequence of slides.): Neutrophils and macrophages eliminate microbes and remove damaged tissue so that repair can begin

 Activated

neutrophils and macrophages kill phagocytosed microbes (and damaged tissue) by action of microbicidal molecules in phagolysosomes 

Three classes of microbicidal molecules are most important 1. React eactiv ive e oxy oxyge gen n spec specie iess (ROS)=highly reactive oxidizing agents that destroy microbes (& other cells) 

Called respiratory burst b/c it occurs during oxygen consumption (cellular respiration)

2. Nitric oxide 3. Prot Proteo eoly lyti ticc enzym enzymes es

(2) (ROS) 

Oxygen (O2) has a major role as the terminal electron acceptor acceptor in mitochondria 



It is reduced from O2 to H2O and resultant energy is harnessed as an electrochemical potential across mitochondrial inner membrane me mbrane

Conversion of O 2 to H2O entails transfer of four electrons three partially reduced species, representing transfers of varying numbers of electrons, are intermediate between O2 and H2O 

These are O2 − = superoxide (one electron); H2O2= hydrogen peroxide (two electrons); OH•= hydroxyl radical (three electrons)

Widmaier, EP . Vander’s Human Physiology : The Mechanisms of Body Function. 13th Ed. McGraw-Hill, 2014.

Scanning electron microscope (SEM) images of a single neutrophil and macrophage (LR) engulfing bacterium.

A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange)

http://upload.wikimedia.org/wikipedia/com http://upload.wikimedia.org/wikipedia/com mons/f/f2/Neutrophil_with_anthrax_copy.jpg

Widmaier, EP. Vander’s Human Physiology : The Mechanisms of Body Function. 13 th Ed. McGraw-

(oxidative burst) 

Primary free radical – –generating system is phagocyte oxidase system  Involves activation of phagocyte NADPH oxidase complex (e.g., in neutrophils, monocytes) which utilizes O2 as a substrate 

Plays an important role in immune response rapid release oxygen species (ROS) of reactive oxygen



NADPH plays a role in both creation and neutralization of ROS



Myeloperoxidase (produces hypochlorite) is a blue-green heme-containing pigment that gives sputum its color

( RedoxRXN ) RedoxRXN )  Phagocyte

oxidase is a multisubunit enzyme that is assembled in activated phagocytes mainly in phagolysosomal membrane  activated by many stimuli, including IFN-γ and signals from TLRs

 Function of

phagocyte oxidase is to reduce molecular oxygen into ROS * such as superoxide radicals (O2−) with reduced form of nicotinamide adenine dinucleotide phosphate phos phate (NADPH) acting as a cofactor

 Superoxide

is enzymatically dismutated into hydrogen peroxide  which is used by enzyme myeloperoxidase to convert normally unreactive halide ions into reactive hypohalous acids (hypochlorit e) that are toxic for bacteria *Other ROS include H2O2= hydrogen

(2)

Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Step 1 2016. McGraw-Hill, 2016.

Oxidative stress  For human life, oxygen

is both a blessing and

a curse 

Without it, life is impossible, but some of its derivatives are partially reduced oxygen species that can react with, and damage, damage, virtually any molecule they reach i.e., ROS (free radicals)

 Reactive 

Oxygen Species

N.B. ROSs causes of cell and tissue injury in many settings (Illust.)

Of note: Increased free radicals in heart can occur post MI reperfusion. Such toxic oxygen radicals are released from neutrophils when blood flow is Copstead LC, Banksia JL. Pathophysiology, 5th Ed . St. Louis,

(3)  

Deficiency of one of components of phagocyte oxidase results in CGD (chronic (chronic granulomat granulomatous ous disease) disease) = an X-linked inherited deficiency Phagocytes can utilize H2O2 generated by invading organisms & convert it to ROS  Catalase-negative bacteria are effectively killed b/c microbes produce small amounts of peroxide leading to microbial death however  CGD patients are at risk for infection by catalase species (e.g., S aureus, Aspergillus [fungus]) capable of neutralizing their own H 2O2 leaving phagocytes without ROS for fighting infections Related notes: Pyocyanin of P. aeruginos ae ruginosa a functions to generate ROS to kill competing microbes Lactoferrin is a protein found in secretory fluids and neutrophils that inhibits

Protectionfromharmfulmicroorganisms 

Complex systems exist to protect body from microorganisms 



Some of these systems are innate and have a broad-based action (non-specific) while others are acquired as result of an adaptive immune response act more specifically

Functions of immune system are carried out by immunoreactive cells circulating within blood and present within tissues (See inflammation section above) as well as by circulating antibodies



Defense against microbes is mediated by early reactions of innate immunity and later responses of adaptive immunity



Innate immunity (also called natural or native defense against immunity) provides early line of defense microbes consists of cellular and biochemical defense mechanisms in place even before infection and respond rapidly to infections 

React to products of microbes and injured cells they respond in same way to repeated exposures



Target structures common to groups of related microbes & do not distinguish fine differences betw microbes (non-specific)



Principal components of innate immunity are 1) physical and chemical barriers such as epithelia and antimicrobial chemicals produced at epithelial surfaces 2) phag phagoc ocyt ytic ic cell cellss (neutrophils, macrophages), dendritic cells, and natural killer (NK) cells and other innate lymphoid cells 3) blo blood prote oteins ins, including complement system and other mediators of inflammation

cont. 

Adaptive immunity (also called specific or acquired immunity) stimulated by exposure to infectious agents and increase in magnitude and defensive capabilities with each successive exposure to a particular microbe  b/c this form of immunity develops as a response to infection and adapts to infection called adaptive immunity

 defining characteristics of adaptive immunity

are specificity,, and  ability to distinguish different substances, called specificity  ability to respond more vigorously to repeated exposures to same microbe, known as memory (anamnestic response)

 unique components of adaptive immunity

are cells called lymphocytes and their secreted products such as antibodies

 There are

two types of adaptive immune responses, called humoral different immunity and cell-mediated immunity mediated by different components of the immune system and function to eliminate different different types of microbes 

Humoral immunity is mediated by molecules in blood and mucosal secretions, called antibodies produced by cells called B lymphocytes (also called B cells) cells) Antibodies recognize microbial antigens, neutralize infectivity of microbes, and o target microbes for elimination by various effector mechanisms



Humoral immunity is the principal defense mechanism against extracellular microbes and their toxins b/c secreted antibodies can bind to these microbes and toxins and assist in their elimination (e.g. bacterial infections) o

Antibodies themselves are specialized and may activate different mechanisms to combat microbes (effector mechanisms)

cont. 

Cell-mediated immunity (also called cellular immunity) is mediated by T lymphocytes (also called T cells)



Intracellular microbes, such as viruses and some bacteria, survive and proliferate proliferate inside phagocytes and other ot her host cells, where they are inaccessible to circulating antibodies 



Defense against such infections is a function of cell-mediated immunity  which promotes destruction of microbes residing in phagocytes or killing of infected cells to eliminate reservoirs of infection

Some T lymphocytes lymphocytes also contribute to eradication of extracellular microbes by recruiting leukocytes that destroy these pathogens and by helping B cells make effective antibodies



Active immunity= immunity= Protective immunity against a microbe is usually induced by host’s host’s response to microbe 





The form of immunity that is induced by exposure to a foreign antigen is called active immunity b/c immunized individual plays an active role in responding to antigen

Individuals and lymphocytes lymphocytes that have not encountered a particular antigen are said to be naïve implying they are immunologically inexperienced; contrastly Individuals who have responded to a microbial antigen and are protected from subsequent exposures to that microbe are said to be immune N.B. Only active immune responses

cont. 

Passive immunity= immunity= Immunity conferred on an individual by transferring serum or lymphocytes from a specifically immunized individual, a process known as adoptive transfer transfer becomes immune to particular  Recipient of such a transfer antigen without ever having been exposed to or having responded to that antigen thus, called passive immunity o



Passive immunization = useful method for conferring resistance rapidly, without having to wait for an active immune response to develop

A physiologically important example of passive immunity  transfer transfer of maternal m aternal antibodies through placenta to fetus enables newborns to combat infections before they develop ability to produce antibodies themselves



Autoimmune diseases occur when immune system attacks attacks ‘self’ ‘self ’ cells and tissues  this is referred to as a breakdown of “immune tolerance”  This leads to inflammation and tissue damage, which may be o highly localized (e.g. type 1 diabetes mellitus) or o generalized (e.g. systemic lupus erythematosus)



Defects may occur within immune system

May be:  congenital (e.g. severe combined immunodeficiency) or chemotherapy, infection with  acquired (e.g. reaction to chemotherapy, human immunodeficiency virus (HIV)) May affect: system or  a specific component of immune system  have more widespread effects within several components 

Defects usually lead to increased susceptibility to a range of infections



There are two major mechanisms by which cells can die  Apoptosis (programmed cell death) is an energy-requiring process leading to death of individual cells, which does not incite an inflammatory reaction o Apoptosis may be physiological or pathological in nature 

Necrosis does not require energy, usually affects groups of cells and typically incites an inflammatory reaction usually acute in nature



Various degenerative processes can occur within cells and tissues as a result of disease states, for example: example:  Calcification may occur if serum calcium conc. is chronically elevated ‘metastatic’ calcification) or within an abnormal tissue (e.g. a tumor or (‘metastatic’ focus of chronic inflammation ‘dystrophic’ calcification 

Amyloid is an insoluble protein with a β-pleated sheet structure that is deposited either locally or in a widespread manner in various chronic disease states such as chronic inflammatory conditions (e.g. tuberculosis) or low-grade neoplasms of B-lymphocyte lineage (e.g. lymphoplasmacytic lymphoma)



Other forms of degenerative change include glycogen accumulation, hyaline change and myxomatous change



Hemosiderin is an iron-containing pigment that may be deposited in tissues following red cell destruction and hemoglobin breakdown (e.g. after a hemorrhage) or w/in organs such as liver in genetic hemochromatosis 

   

hemosiderin granules impart yellow to brown color of healing bruise

Lipofuscin (or lipochrome) lipochrome) is a wear-and-tear pigment that is deposited in organs such as heart and liver Melanin is produced by melanocytes in skin and is commonly found in tumors showing melanocytic differentiation (e.g. malignant melanoma) Bilirubin is a bile pigment that accumulates in jaundice, either in conjugated or unconjugated form (yellow sclera & skin= icterus) Anthracosis is a black color comes from carbon pigments in dust inhaled over years, engulfed by macrophages, and sent via lymphatics l ymphatics to nodes 

It looks bad but does not compromise lung function







characterized by a fast pulse rate Shock is a clinical condition characterized (usually > 100 beats/min) and a low blood pressure (systolic blood pressure usually < 100 mmHg) Common types of shock are  hypovolemic (low blood volume, e.g. in hemorrhage), myocardial infarction)  cardiogenic (heart pump failure, e.g. in myocardial  septic (severe infection) Less common types are hypersensitivity reaction, e.g. penicillin  anaphylactic (type I hypersensitivity allergy)  neurogenic (loss of sympathetic vasomotor tone, e.g. in a spinal cord injury)



Body possesses many mechanisms that aim to protect against against potentially injurious agents  These mechanisms may be o Behavioral o Anatomical or o Immunological



Congenital diseases are those that are present at birth



Inherited diseases are those passed on from parents via transfer of a genetic defect (e.g. familial adenomatous polyposis)



Congenital diseases may be inherited from parents but may also occur though chromosomal abnormalities that originate during gametogenesis or fertilization (e.g. Down’s syndrome) or ‘insults’ sustained by fetus before birth (e.g. congenital infections)

Neoplasia



Neoplasia means “new growth” and indicates presence of cells or tissues showing evidence of abnormally controlled or disordered growth



Neoplasms comprise cells that show differentiation along one or more pathways of development

Benign vs Malignant  Benign neoplasms expand locally but do not invade adjacent tissues or spread to distant sites , while  Malignant neoplasms (cancers) invade adjacent tissues and spread to distant sites

(2)  





proliferation of cells Neoplasia Uncontrolled, clonal proliferation  Can be benign or malignant Dysplasia Disordered, non-neoplastic cell growth  Used only with epithelial cells  Mild dysplasia is usually reversible  Severe dysplasia usually progresses to carcinoma in situ Differentiation degree to which a malignant tumor resembles its tissue of origin Well-differentiated tumors closely resemble their tissue of origin  Well-differentiated differentiated look almost nothing like their tissue of origin  poorly differentiated Anaplasia Complete lack of differentiation of cells in a malignant neoplasm

(3) 

Genetic and environmental factors influence development of neoplasia  Most germline (i.e. inherited and present in all cells) genetic influences on neoplasm development are polygenic in nature, while  A minority of neoplasms occur in association with a clearly defined inherited defect in a single gene (monogenic)



Neoplasms vary in their relative incidence between populations and different geographical areas as a result of differences in gene pools and environmental contributors to disease development

(4) 

Neoplasm development development is characterized by accumulation of genetic defects within neoplastic cells 

In some neoplasms, this sequence is well characterized



In others specific genetic mutations are found sufficiently commonly that their detection may be used to confirm the diagnosis of tissue type or to help to determine likely biological behavior of neoplasm (i.e. how aggressively the neoplasm is likely to grow)

(5) 

Benign tumors may compress adjacent tissue but do not invade it



Malignant tumors grow locally, infiltrate adjacent tissue and metastasize metastasize via lymphatic channels and blood vessels to distant sites



Benign tumors can cause death by compressing vital structures (e.g. within brainstem) but otherwise generally generally possess a much better prognosis than malignant tumors

(6) 

Malignant tumors commonly cause extensive local tissue damage but tumor metastasis to distant sites is often key process that causes death in advanced malignancy



Benign and malignant tumors may also produce chemicals such as hormones and, therefore, be associated with clinical symptoms of hormone excess excess  Called a “paraneoplastic syndrome”

(7)  Clinical

and pathological features of neoplasms can indicate whether they are benign or malignant in nature

 Histopathological

examination of malignant neoplasms is important to determine how aggressively neoplasm is likely to grow and metastasize

 Features

such as  tumor type  grade (histological assessment of aggressiveness)  size and  presence of lymph node metastases are most commonly assessed features used to predict biological behavior of malignant neoplasms

(8) 

Most cancers (>90%) arise from "epithelial" tissues , such as inside lining of colon, breast, lung or prostate prostate  These are referred to as carcinomas and usually affect older people  Contrastly, sarcomas are tumors that arise from "mesenchymal" tissues such as bone, muscle, connective tissue, cartilage and fat

(9) 

Lung cancer is an aggressive neoplasm for which cigarette smoking is major risk factor

 Almost all lung cancers cancers are carcinomas carcinomas 

Neoplasm can invade local structures including mediastinum and chest wall and commonly metastasizes to distant sites



Many patients present when disease is at an advanced local stage or with widespread widespread metastases metastases and when surgical removal is not possible

Klatt EC. Robbins and Cotran Atlas of Pathology , 3rd Ed. Philadelphia: Saunders, 2015.




Bronchogenic carcinoma, gross The large carcinoma ( ) in the upper lobe is arising in a lung with centriacinar emphysema, suggesting cigarette smoking as the risk factor There are patchy infiltrates in lower lobe pneumonia, likely from central representing pneumonia, airway obstruction by this large mass congestion, likely There is inferior congestion, exacerbated by heart failure


(10) 

Breast cancer is second most common malignancy in women (only exceeded by lung cancer in populations where cigarette smoking is common)

breast cancers are are carcinomas  Almost all breast 

Most often present as breast masses and invade local structures including skin and breast wall as well as metastasizing to local lymph nodes and distant sites



While breast cancer is an important cause of mortality among middle aged and older women modern advances in therapy have significantly improved outcome





(11) 

Colorectal cancer is one of three most common cancers in Western populations 

it is likely that environmental factors, including Western diet with low roughage, contribute to this

colorectal cancers cancers are carcinomas carcinomas  Almost all colorectal 

These neoplasms grow locally and pts. may present w rectal bleeding, a change in bowel habit or w acute abdominal symptoms caused by bowel obstruction or perforation  Metastasis to local lymph nodes and distant sites (most commonly liver) may occur  Surgical removal when disease is localized to bowel wall is often associated with a favorable outc




(12) 

Prostatic cancer is increasing in incidence among middle-aged and elderly men although this may partly reflect increased detection of disease in its early stages in screening programs

prostatic cancers cancers are carcinomas carcinomas  Almost all prostatic 

May invade local pelvic structures and metastasize to distant sites, especially bone  While advanced prostatic cancer is commonly fatal, localized disease (most commonly identified by screening) may be curable with prostatectomy  Progression of advanced disease may be slowed with













(13) 

Certain neoplasms occur primarily in childhood  e.g. neuroblastoma and nephroblastoma



Elderly individuals develop wear-and-tear diseases   osteoarthritis atherosclerosis-associated conditions e.g.  atherosclerosis-associated ischemic heart disease [IHD]) and



Elderly individuals are at increased risk of many neoplasms

(14) 

Neoplasm development is commonly associated with genetic abnormalities within neoplastic tissue  however, proportion of neoplasms that occur as a result of a single inherited germline genetic abnormality (i.e. a mutation present within all of cells making up an individual) is relatively low  Examples include inherited predispositions to breast cancer and colorectal cancer o Although relatively uncommon, these inherited syndromes are important since affected individuals may develop cancer at a young age and sometimes develop multiple cancers o

Identification of affected families may allow cancer prevention programs and/or detection of cancers at an early stage

(15) Grade Degree of cellular differentiation and mitotic activity on histology differentiated) to high grade  Range from low grade (well differentiated) (poorly differentiated, undifferentiated undifferentiated or anaplastic) Stage  Degree of localization/spread based on site and size of 1° lesion, spread to regional lymph nodes, presence of metastases  Based on clinical (c) or pathology (p) findings Example: cT3N1M0  Stage almost always has more prognostic value than grade

TNMstagingsystem TNM staging system ( Stage = Spread): T = Tumor size N = Node involvement M = Metastases  Each TNM factor has independent prognostic value M factor often most important 

Diseasescreening 

Disease screening means attempting to detect disease processes at an early (asymptomatic) stage when prompt treatment should result in an improved prognosis  Diseases are required to fit various criteria in order to be suitable for screening



US screening programs are currently in place for  neoplastic diseases such as breast & cervical cancer & for hypothyroidism  non-neoplastic non-neoplastic diseases such as neonatal hypothyroidism and phenylk ph enylketonuria etonuria (PKU)

 Body is particularly

susceptible to certain conditions

at extremes of age For example  Premature babies possess immature body systems and are prone to infections and specific difficulties associated with organs that are not fully developed (e.g. respiratory respiratory failure, gut failure)  Elderly individuals are at increased risk of many neoplasms, atherosclerosis-associated conditions, osteoarthritis etc.

Cardiovascular System







Atherosclerosis is a very common disease process occurring within arteries, especially large elastic arteries and their major branches ‘fatty streaks’ within arterial  Earliest lesions comprise ‘fatty intima Established atherosclerotic plaques comprise a “cap” of fibrous tissue beneath which are pools of fat, foamy macrophages and smooth muscle cells Dystrophic calcification is common in older lesions  Plaque surface may ulcerate (plaque rupture)  leading to a thrombus that coats plaque acute vascular occlusion Atherosclerosis osis and Thrombosis Illustrated Notes - Offline See: Atheroscler

 Arteriosclerosis

is a general term for several disorders that cause thickening and loss of elasticity in the arterial wall form, is  Atherosclerosis, the most common form, also most serious b/c it causes coronary artery disease and cerebrovascular disease

Normal coronary artery, artery, microscopic

 Atherosclerosis

is patchy intimal plaques (atheromas) in medium-sized and large arteries 

plaques contain lipids, inflammatory cells, smooth muscle cells, and connective tissue Coronary artery with atherosclerotic

F r o m : W e b p a t h C a r d i o v a s c u l a r P a t h o l o g y i m a g e p l a t e s

(IHD) 

IHD is leading cause of death among adults within Western populations 

It occurs secondary to narrowing of one or more of coronary arteries most commonly as a result of atherosclerotic changes



Ischemic heart disease commonly results in angina and may lead to myocardial infarction and/or cardiac failure



Sudden death may occur with or without evidence of MI



Anatomic Diagnosis = Atherosclerosis (ASHD)



Etiologic Diagnosis = Coronary Heart Disease (CHD, IHD, CAD)



Physiologic Diagnosis = e.g., Angina Pectoris



Functional Diagnosis = Stable vs Unstable Angina vs MI [STEMI vs NSTEMI]=ACS

 Coronary

heart disease  proper circulation of blood and oxygen are not provided to heart and surrounding tissue  due

to a narrowing of small blood vessels, which normally supply heart with blood and oxygen

cause of coronary heart disease is atherosclerosis takes place with plaque and fatty build up on artery walls narrowing vessels

 Typical

 When excess cholesterol deposits on cells and on

the inside walls of blood vessels it forms an atherosclerotic plaque  First step of atherosclerosis is injury to

endothelium  results in atherosclerotic lesion formation plaque ruptures blood clots form to decreased blood flow resulting in cardiovascular events (ACS/MI)

 When

lead

F r o m : W e b p a t h C a r d i o Coronary artery, mild atherosclerosis, gross v a s c u l a r P a t h o l o g y i m a g e p l a t e s Coronary artery, severe atherosclerosis, gross

 Symptoms

develop when growth or rupture of plaque reduces or obstructs blood flow

 Diagnosis is

clinical and confirmed by angiography angio graphy,, or other imaging tests

 Treatment

includes risk factor management and dietary modification, physical activity, antiplatelet drugs, and

Heart and LAD coronary artery with recent thrombus, gross  Anterior surface of heart demonstrates demonstrates an opened left anterior descending coronary artery  Within lumen of coronary can be seen a dark red recent coronary thrombosis  The dull red color to myocardium as seen below glistening epicardium to lower right of thrombus is consistent with underlying myocardial infarction From: Webpath Cardiovascular Pathology image plates



Risk factors factors atheroscler atherosclerosis osis include: include:         

Dyslipidemia (hypercholester (hypercholesterolemia olemia /LDL-C) diabetes mellitus cigarette smoking family history sedentary lifestyle obesity Hypertension Positive Family Hx CVD & premature death Lipoprotein(a) [abbreviated Lp(a)] o

Apparently, only men, but not women, are affected by this risk

Coronary heart disease Tx methods may include: (depends on presenting Physiologic Dx)

1. Angioplasty with stenting stenting 2. 3. 4. 5. 6. 7.

Coronary artery bypass surgery (CABG) Medication Minimally invasive heart surgery Proper diet and exercise Quitting smoking Treatment of other comorbidities, HTN, DM, Obesity




Apart from ischemic heart disease, atherosclerosis also commonly affects carotid and intracranial arteries leading to cerebrovascular cerebrovascular disease (e.g. strokes [CVA], vascular dementia) while



aortic and iliac artery atherosclerosis atherosclerosis leads to aortic aneurysm formation and peripheral vascular disease (e.g. intermittent claudication and foot gangrene)




Thrombosis occurs after activation of clotting cascade and is a vital physiological physiological mechanism for limiting blood loss when hemorrhage occurs



Thrombosis occurring as part of a disease process lead to local vascular occlusion (e.g. coronary artery thrombosis) or to distant vascular occlusion (thromboembolism, e.g. pulmonary thromboembolism secondary to deep vein thrombosis)




An embolism occurs when an embolus migrates migrates from one part of body and causes a blockage of a distant blood vessel  embolus can be made up of materials other than a thrombus, for example o Air o Amniotic fluid o Fat or o Tumor tissue




The mitral and aortic valves are valves most commonly affected by degenerative disease in adults  Stenosis or incompetence of these valves may lead to cardiac failure and (apart from mitral stenosis) left ventricular cardiac hypertrophy  aortic stenosis is a not uncommon cause of sudden death 

Rheumatic fever is an important cause of mitral valve stenosis in older patients



Damaged cardiac valves are prone to secondary bacterial infection (endocarditis) which itself can lead to further valvular damage





myocardium such as viral myocarditis Unusual conditions of myocardium and cardiomyopathy (e.g. hypertrophic cardiomyopathy) are important causes of sudden death in young adults adul ts 





Obstructive hypertrophic cardiomyopathy (subset) asymmetric septal hypertrophy and systolic anterior motion of mitral valve, outflow obstruction, dyspnea, possible syncope In hypertrophic cardiomyopathy diastolic dysfunction ensues

Cardiomyopathies may result from a genetic defect or secondary to cardiac muscle damage, following, for example  

viral myocarditis or cardiomyopathy) chronic excess alcohol consumption (dilated ( dilated cardiomyopathy) o In dilated cardiomyopathy systolic dysfunction ensues



There are many forms of congenital heart disease resulting in  anatomical anatomical abnormalities of heart (e.g. ventricular septal defect, valvular atresia) and  associated structures (e.g. patent ductus arteriosus)



Congenital heart defects leading to introduction of systemic venous blood directly into systemic arterial circulation commonly cause cyanosis


 

Cardiac failure occurs when heart is unable to eject blood sufficiently effectively during systole Common causes of heart failure include 

ischemic heart disease  cardiac valvular disease  hypertensive heart disease  chronic lung disease   

N.B. Under conditions of poor tissue perfusion, perfusion, there will be more anaerobic glycolysis and more acidosis in cells throughout the body. The blood lactate rises in this condition.

Less common causes include pericardial constriction and dilated cardiomyopathy LV cardiac failure results in pulmonary vascular congestion and edema (PE) RV cardiac failure produces a raised jugular venous pressure, hepatic venous congestion peripheral edema




 

Hypertension is common, often asymptomatic and has many causes including  Stress  Obesity  Renal artery stenosis and  Hormonal defects such as Cushing’s syndrome and Conn’s syndrome Chronic hypertension is characterized by an imbalance in sodium and water homeostasis Untreated hypertension can lead to accelerated atherosclerosis and to end-organ damage, including hypertensive nephropathy, hypertensive heart disease and intracerebral hemorrhage





Respiratory Respirat ory Syst System em

 Pneumonia

means inflammation within lung and most commonly occurs as a result of an infection



Many microorganisms may infect lung tissue, but among most common are viruses and bacteria:  bacteria resulting in most common and severe forms of pneumonia

(2) 

Pneumonia may be acquired within community or while in hospital and these circumstances circumstances are associated with different infective organisms



involve Pneumonia may primarily involve  one pulmonary lobe (lobar pneumonia) or be  more widespread and centered on respiratory bronchioles (bronchopneumonia) o Bronchopneumonia is a common terminal event in pts. w other serious diseases



  





Tuberculosis affects millions of individuals worldwide and most commonly occurs in developing countries There is a strong association between tuberculosis and HIV infection particularly in Africa Tuberculosis is caused by Mycobacterium Mycobacterium tuberculosis bacterium and is classically associated w extensive tissue necrosis and granulomatous inflammation TB Infection may be localized (e.g. to lung) or widespread  latter is commonly fatal Treatment usually requires prolonged therapy with multiple special antibiotics

 Ghon

complex is typical of primary tuberculosis tuberculosis and consists of a subpleural granuloma, usually involving lower part of upper lobe or upper part of lower lobe, and ipsilaterally enlarged hilar lymph nodes, which also contain tuberculous granulomas

 Secondary tuberculosis (Sec)

typically presents in form of apical lesions

Damjanov I, Pathology Secrets 3rd ed. Mosby-Elsevier, 2009.










COPD is characterized by presence of  emphysema (lung tissue destruction) and  chronic bronchitis (excess bronchial mucus and airway wall thickening) in variable proportions There is a strong association with cigarette smoking



Disease is chronic, results in an ‘obstructive’ ‘obstructive’ pulmonary function defect & is often complicated by pulmonary infection



Death eventually occurs through respiratory failure, sepsis or right ventricular cardiac failure






Asthma is a reversible obstructive pulmonary airway defect associated with bronchial smooth muscle hypersensitivity and excess bronchial mucus production



An acute asthma attack is characterized by bronchoconstriction and airway blockage by mucus plugs  leads to wheezing and in very severe cases respiratory failure (status asthmaticus)



Treatment with inhaled bronchodilators (e.g. β2adrenoceptor agonists) and anti-inflammatory agents (e.g. inhaled steroids) is effective in majority of pts.







Diseases that make lung tissue stiffer result in restrictive restrictive lung disease:  lungs are unable to expand fully and total lung capacity (TLC) is reduced



Conditions most commonly associated with a restrictive restrictive lung function defect include fibrosis (e.g. cryptogen cryptogenic ic fibrosing fibrosing alveoliti alveolitiss, asbestosis)



Gastrointestinal Syst System em



Chronic GERD (gastroesophageal (gastroesophageal reflux disease) with esophageal mucosal injury can lead to metaplasia of normal esophageal squamous mucosa into gastrictype columnar mucosa, but with intestinal-type goblet goblet cells= cells= known as Barrett Barrett esophagus esophagus



Ten percent of patients with chronic gastric reflux may develop Barrett esophagus



Ulceration leads to bleeding and pain  inflammation






(PUD) 

PUD is common in Western populations and involves mucosal ulceration within stomach and duodenum

 Helicobacter pylori

infection is by far the most common

underlying cause 

Peptic ulcers cause abdominal pain while complications include GI hemorrhage and perforation of gastric or duodenal wall  Perforation usually causes peritonitis but  Perforation into pancreas may cause acute pancreatitis

Drake RL, et al. Gray’s Atlas Of Anatomy, 2 nd Ed. Churchill Livingstone, 2015.










Malabsorption of nutrients from food may be caused by  pancreatic exocrine insufficiency (e.g. chronic pancreatitis) or  a specific or generalized defect w/i luminal GIT o

o

Specific defects include pernicious anemia [damage to intrinsic factor (IF)] producing parietal cells w/i specialized gastric mucosa) generalized defects include post-infectious diarrhea (damage to small intestinal microvillous brush border)

Gallstones are very common  They occur when c holesterol or bile pigments crystallize within concentrated concentrated bile and usually form within gallbladder 



Complications include  acute and chronic cholecystitis  obstructive jaundice and  acute pancreatitis





Acute pancreatitis is a potentially life-threatening life-threatening condition that most commonly occurs secondary to alcohol abuse and/or a nd/or gallstones gallstones



Chronic pancreatitis is an insidious condition that most commonly develops secondary to chronic alcohol abuse



Both conditions can  lead to pancreatic exocrine (and sometimes endocrine ) insufficiency







 T1DM occurs

secondary to autoimmune destruction of pancreatic insulin producing beta cells in islet 

T1DM develops most commonly in children and young adults as a result of a combination of an inherited genetic predisposition to autoimmune disease plus a triggering factor that may be a viral infection

cont. 

T2DM occurs primarily though increasing resistance of peripheral tissues to insulin and it typically develops in middle-aged and elderly people  where it is closely associated with obesity



DM may also also occur as a secondary secondary phenome phenomenon non in Cushing’s disease or as a side effect conditions such as Cushing’s of treatments such as steroid therapy



Acute complications of DM include hyperglycemia hyperglycemia with ketoacidosis (type 1 diabetes) or hyperosmolar hyperosmolar coma (type 2 diabetes) and hypoglycemia 



hypoglycemia occurs occurs secondary to therapy t herapy (i.e. insulin replacement in type 1 or o r oral hypoglycemic agents in type 2)

Chronic complications of DM include an increased susceptibility to infections, accelerated atherosclerosis and microvascular angiopathy  leading to retinopathy and forming a component of diabetic nephropathy



Fatty change is a common liver condition with many causes, including excess alcohol consumption, DM, obesity, drug reactions and various other forms of metabolic disturbance



Cirrhosis is nodular transformation transformation of liver characterized by hepatocyte regeneration together with bands of fibrous scar tissue 

causes for cirrhosis include chronic alcohol abuse, viral hepatitis and autoimmune conditions (e.g. autoimmune hepatitis, primary biliary cirrhosis)

Klatt EC. Robbins and Cotran Atlas of Pathology , 3rd Ed.







Cirrhosis diffuse bridging fibrosis and regenerative regenerative nodules disrupt normal architecture of liver  increase risk for hepatocellular carcinoma (HCC)  Etiologies include alcohol (60 –70% of cases in US), nonalcoholic steatohepatitis, chronic viral hepatitis, autoimmune hepatitis, biliary disease, genetic / metabolic disorders



Portal hypertension increase pressure in portal venous system  Etiologies include cirrhosis (most common cause in Western countries), vascular obstruction (e.g., portal vein thrombosis, thrombosis, Budd- Chiari syndrome), syndrome), schistosomiasis

Le T and Bhushan V. Microbiology. In: First Aid for the



Renal Syst System em

UTIs are much more common in females than males and usually occur secondary to infection with fecal bacteria such as Escherichia coli  Infections commonly involve bladder (causing cystitis) but may also involve kidneys (causing pyelonephritis) 

Predisposing factors factors include female gender, urinary calculi and urinary stasis  UTIs are a common cause of septicemia , especially within the elderly 





Glomerulonephritis means inflammation centered on glomeruli remainder of nephron may show secondary changes



Glomerulonephritis may occur as an acute or chronic condition and  causes  nephritic syndrome (especially in children)  nephrotic syndrome and  renal failure (acute and chronic)



There are multiple causes and several distinct histological subtypes, each with a different clinical outcome








Nervous System



Raised ICP may occur secondary to intracranial intracranial hemorrhage (usually acute onset) or as a result of a space-occupying lesion such as a neoplasm (usually gradual onset) 

Early effects include cranial nerve compression (e.g. third nerve compression leading to pupillary dilatation dilatation)



Later effects include herniation of brain tissue through an anatomical aperture (e.g. the foramen magnum), which when severe may lead to brainstem compression and death








Le T and Bhushan V. Microbiology. In: First Aid for the USMLE Step 1 2016. McGraw-Hill, 2016.





CVA present clinically as sudden neurological defects and may be caused by  



intracranial hemorrhage (e.g. subarachnoid or intracranial intracranial hemorrhage) or cerebral infarction (usually secondary to thrombotic or embolic occlusion of a carotid or intracranial artery)

Strokes may lead to death or permanent severe neurological defects  but modern therapies can result in remarkable clinical recovery



Dementia is a progressive global decline in intellectual capacity that occurs with increasing frequency with advancing age



Two most commonly encountered forms are  Alzheimer’s disease (AD) (sometimes familial) and  Vascular (multi-infarct) dementia (VaD)



Less common dementias are Huntington’s disease (an inherited condition) and Pick’s disease










Multiple vascular events, including embolic arterial occlusion, atherosclerosis with vascular narrowing and thrombosis, and hypertensive arteriolar sclerosis may lead to focal but additive loss of cerebral tissue Cumulative effect of multiple small areas of infarction ( ) may result in clinical findings equivalent to AD along with focal neurologic deficits or gait disturbances Vascular dementia marked by loss of higher mental function in a stepwise, not continuous, fashion

Musculoskeletal System



Osteoporosis is loss of bone matrix (density) and most commonly occurs in postmenopausal women  hormone replacement therapy is an important prophylaxis prophylaxis against its development



Osteomalacia is loss of bone mineralization and occurs b/c of poor dietary vitamin D intake or defects in vitamin D and calcium metabolism (e.g. chronic renal failure)



Osteoporosis and osteomalacia predispose to fractures especially of hip, wrist and thoracolumbar spine

Bone mineral density (BMD) is best assessed imaging , and with radiologic imaging, dual-energy x-ray absorptiometry (DEXA ( DEXA)) scans  provide a standardized way of assessing risk for fracture from osteoporosis  A graphical display of a DEXA scan for hip (femur) comparing BMD age and T-score (in 

standard deviations above or below comparable woman’s mean BMD) healthy young adult woman’s  The asterisk representing a woman at age 48 is within expected range for age  The circle marks BMD for a woman age 60 and is concerning for greater bone loss from osteopenia (−1 to −2.5) but not yet osteoporosis  The X marks the BMD for a woman age 76 and is in range of osteoporosis (exceeding − 2.5) with






Osteoarthritis is a wear-and-tear condition most commonly affecting affecting major weight-bearing joints and characterized by erosion of articular cartilage and osteophyte formation



Predisposing factors factors include ‘excess’ physical activity (e.g. sports people) and prior damage to joint or associated bones both result in abnormal joint stresses


(RA) 

Rheumatoid arthritis is a multisystem multisystem disorder comprising a symmetrical inflammatory polyarthritis extra-articular manifestations manifestations including together w extra-articular pulmonary fibrosis and subcutaneous nodules



Endocrine System

Endocrine hormones are key key factors in regulation of metabolism , and correct regulation of their production is essential  Excess endocrine hormone production results in conditions such as glucocorticosteroids)  Cushing’s syndrome (excess glucocorticosteroids)  Conn’s syndrome (excess mineralocorticoids) thyroid hormone) and Graves’ disease dise ase (excess thyroid  Graves’  Acromegaly (excess growth hormone)  Insufficient endocrine hormone production results in conditions such as  Addison’s disease (insufficient corticosteroids) and Hypothyroidism 

Practice Q&A

A 45-year-old man has had a fever and dry cough for 3 days, days, and now has difficulty breathing and a cough productive of sputum. On physical examination examination his temperature is 38.5 C. Diffuse rales are auscultated over lower lung fields. A chest radiograph shows a right pleural effusion. A right thoracentesis is performed. The fluid obtained has a cloudy appearance with a cell count showing 15.500 leukocytes per microliter, microliter, 98% of o f which are a re neutrophils. Which of the following terms best describes his pleural process? A Serous inflammation B Purulent inflammation C Fibrinous inflammation D Chronic inflammation

(A) Incorrect. A transudate in a serous effusion has few cells. (B) CORRECT. CORRECT. The neutrophils suggest an acute process; the fluid is characteristic for for an exudate. Such a large la rge amount of purulent exudate in the pleural space can be termed an empyema. (C) Incorrect. Fibrin can often accompany acute inflammatory processes, but a process with so s o many neutrophils is best characterized characterized as a purulent exudate. (D) Incorrect. Chronic inflammation has a preponderance of mononuclear cells, not neutrophils. (E) Incorrect. A granulomatous response is characterized characterized by mononuclear cells.

A 56-year-old man has had increasing difficulty breathing for for the past week. On physical examination he is afebrile. Auscultation of his chest reveals diminished breath sounds and dullness to percussion bilaterally. bilaterally. There is 2+ pitting edema present to the level of his thighs. A chest radiograph reveals bilateral bilateral pleural effusions. Which of the following laboratory test findings is he most likely to have? A Hypoalbuminemia B Glucosuria C Neutrophilia D Anemia E Hypernatremia

(A) CORRECT. The decrease in oncotic pressure from decreased serum albumin, the blood protein that accounts for most of the oncotic pressure, can be significant. This can be a cause for edema and fluid transudates. Too little circulating protein doesn't keep in or draw water into the vasculature (B) Incorrect. Glucosuria with diabetes mellitus can explain loss of free water with dehydration, not edema. (C) Incorrect. Neutrophilia suggests an acute inflammatory response, which can produce localized edema in the area of inflammation. (D) Incorrect. Anemia reduces oxygen carrying capacity; if severe, it could eventually lead to a high output congestive heart failure that would initially involve mainly the left heart, with consequent pulmonary congestion and edema. (E) Incorrect. An increased serum sodium suggests loss of free water and dehydration, not edema.

43. A 48-year-old woman goes to her physician for a routine physical examination. examination. A 4 cm diameter non-tender mass is palpated in her right breast. The mass appears fixed to the chest wall. Another 2 cm non-tender mass is palpable in the left axilla. A chest radiograph reveals reveals multiple 0.5 to 2 cm nodules in both lungs. Which of the following classifications best indicates the stage of her disease? A T1 N1 M0 B T1 N0 M1 C T2 N1 M0 D T3 N0 M0 E T4 N1 M1

(A) Incorrect. This classification is for a small primary cancer with nodal metastases but no distant metastases. metastases. (B) Incorrect. This classification is for a small primary cancer with no lymph node metastases but with distant metastases. (C) Incorrect. This classification is for a larger primary cancer with nodal metastases but no distant metastases. metastases. (D) Incorrect. This classification is for a larger primary cancer with no metastases to either lymph nodes or to distant sites. (E) CORRECT. CORRECT. She has a large invasive (high T) primary tumor mass with axillary node (N > 0) and lung metastases (M1).

Review of a series of surgical pathology reports indicates that a certain type of neoplasm is diagnosed as grade I on a scale of I to IV. Clinically, Clinically, some of the patients with this neoplasm are found to have stage I disease. Which of the following is the best interpretation of a neoplasm with these designations? A Unlikely to be malignant B Arising from epithelium C May spread via lymphatics and bloodstream D Has an in situ component E Well-differentiated Well-differentiated and localized

(A) Incorrect. Criteria for malignancy must be satisfied first, then grading and staging follow. (B) Incorrect. Grading and staging are most useful for epithelial epithel ial malignancies, but are not reserved specifically for them. (C) Incorrect. It may indeed spread to lymph nodes, particularly if it is a carcinoma, or distant sites, but is less likely to do so if it has a low grade and it remains small and localized. (D) Incorrect. It may have an in situ component, but the behavior of most neoplasms is judged by the worst part of it, and stage I puts it beyond in situ. (E) CORRECT. CORRECT. A well-differentiated well-differentiated and localized lo calized neoplasm usually has both a low grade and low stage. In such cases surgery is more likely to be

A 55-year-old man has a 30-year history of poorly controlled diabetes mellitus. He has had extensive black discoloration of skin and soft tissue of his right foot, with areas of yellowish exudate, for the past 2 months. Staphylococcus aureus is cultured from this exudate. A below-the-knee amputation is performed. The amputation specimen received in the surgical pathology laboratory is most likely to demonstrate which of the following pathologic abnormalities? A Neoplasia B Gangrene C Coagulopathy D Hemosiderosis

(A) Incorrect. A neoplasm is a mass lesion. (B) CORRECT. Gangrenous necrosis is a typical complication of diabetes mellitus with marked peripheral vascular disease. Gangrene is a form of coagulative necrosis that involves a body part, including several tissues. The infection adds an element of liquefactive necrosis, best described as 'wet gangrene. (C) Incorrect. Such a d disorder isorder,, with either thrombosis or hemorrhage, would be more likely manifested throughout the body. Coagulopathy is not a feature of diabetes mellitus (D) Incorrect. Hemosiderin may form locally from remote hemorrhage. With iron overload, it collects in tissues of the mononuclear phagocyte system. (E) Incorrect. Caseation is a part of granulomatous inflammation.

The lifestyle patterns of healthy persons from 20 to 30 years of age are studied. A subset of these persons have a lifestyle characterized characterized by consumption of a lot of pizza and very little physical exercise. Which of the following tissue changes is most likely to develop in this subset of persons as a consequence of this lifestyle? A Fatty metamorphosis of liver B Pancreatic fat necrosis C Fatty degeneration of myocardium D Hypertrophy of adipocyte E Metaplasia of muscle to adipose tissue

(A) Incorrect. Fatty change in the liver is due du e to toxic and metabolic derangements, such as those that occur with malnutrition malnutri tion or alcoholism. (B) Incorrect. Pancreatic fat necrosis may occur from injury from inflammation or trauma. (C) Incorrect. Fatty change in the heart is a consequence of toxic or hypoxic events. (D) CORRECT. CORRECT. The fat cells (adipocytes) increase i ncrease in size (hypertrophy) with obesity in adults, and this is the predominant effect of weight gain. (E) Incorrect. Muscle does not typically undergo metaplasia in response to weight gain. Adipocytes in fascial planes and around the muscle can increase in size. The muscle may atrophy in response to the sedentary lifestyle.

A 44-year-old woman has had episodes of right upper quadrant pain during the past 2 weeks. Her stools have become pale in color over the past 3 days. Laboratory Laboratory studies show a serum total bilirubin of 9.7 mg/dL. A cholangiogram shows that a gallstone has passed into the common bile duct, resulting in obstruction of the biliary tract. Which of the following cellular alterations is most likely to be visualized on her skin surfaces? A Hemosiderosis B Calcification C Lipofuscin deposition D Icterus E Steatosis

(A) Incorrect. Excessive iron can be accumulated through increased absorption, increased intake, intake, or prolonged transfusion therapy. therapy. (B) Incorrect. Dystrophic calcification calcification can occur in areas of tissue damage, as in granulomatous diseases. The liver is not a typical spot for metastatic calcification. calcification. (C) Incorrect. Steatosis occurs with direct injury to hepatocytes, not biliary tract obstruction (D) CORRECT. CORRECT. She probably has a 'jaundiced' appearance ap pearance to her sclerae and skin due to the increased amount of bilirubin. The bile pigments impart a yellow color to the tissues. She has biliary tract obstruction from cholelithiasis and choledocholithiasis. (E) Incorrect. Fatty change is a process that occurs in the liver, liver, and biliary tract obstruction does not typically cause it.

A 45-year-old man has a traumatic injury to his forearm and incurs extensive blood loss. On physical examination in the emergency department his blood pressure is 70/30 mm Hg. Which of the following cellular changes is most likely to represent irreversible cellular injury as a result of this injury? A Epithelial dysplasia B Cytoplasmic fatty metamorphosis C Nuclear pyknosis D Atrophy E Anaerobic glycolysis F Autophagocytosis

(A) Incorrect. Although dysplasia can be a premalignant condition, it is still reversible. (B) Incorrect. Fatty change is potentially a reversible condition. (C) CORRECT. CORRECT. The hypotension leads to diminished tissue tiss ue perfusion with ischemic injury. Nuclear chromatin clumping is reversible, but nuclear nuclear pykno pyknosis sis is not. (D) Incorrect. 'Downsizing' of the cell in atrophy is reversible. (E) Incorrect. A lack of sufficient oxygen may may lead to anaerobic metabolism, but this can be temporary until the hypoxia is relieved. (F) Incorrect. Incorrect. The cell 'downsizes' 'downsizes' with autophagocytosis of cytoplasmic organelles, via its own lysosomes, but the cell does not die.

A 73-year-old man suffers a "stroke." "stroke." On physical examination examination he cannot move his right arm. A cerebral angiogram demonstrates demonstrates occlusion of the left middle m iddle cerebral artery. artery. An echocardiogram reveals a thrombus within a dilated left atrium. Which of the following is the most llikely ikely pathologic alteration alteration from this event that has occurred in his brain? A Cerebral softening from liquefactive l iquefactive necrosis B Pale infarction with coagulative necrosis C Predominantly the loss of glial cells D Recovery of damaged neurons if the vascular supply is reestablished E Wet gangrene with secondary bacterial infection

(A) CORRECT. CORRECT. Liquefactive necrosis typifies brain infarction. The brain tissue contains abundant lipid. After the initial softening, tissue macrophages will increase and clear the debris, leaving a cystic space. Since neurons cannot regenerate, regenerate, the size of the infarct determines the amount of functional loss. The brain has some capacity for rewiring, but this diminishes with age. (B) Incorrect. Infarction of most organs is accompanied by coagulative necrosis, but not the brain. (C) Incorrect. Neurons are far more sensitive to hypoxia than glial cells. (D) Incorrect. It is unlikely that the vascular supply can be reestablished in a matter of minutes. (E) Incorrect. Gangrenous necrosis is more typical of a body part,

A 30-year-old woman is claiming in a civil lawsuit that her husband has abused her for the past year. year. A workup by her physician reveals a 2 cm left breast mass. There is no lymphadenopathy. lymphadenopathy. No skin lesions are seen, other than a bruise to her upper arm. An excisional biopsy of the breast mass is performed. On microscopic examination, the biopsy shows fat necrosis. This biopsy result is is most consistent with which of the following etiologies? A Physiologic atrophy B Breast trauma C Lactation D Radiation injury E Hypoxic injury

(A) Incorrect. At age 30 she is premenopausal. (B) CORRECT. CORRECT. Fat necrosis is seen with trauma to the breast, and her lawyer will make good use of that documentation. The pattern of multiple injuries of differing ages at different sites suggests abuse. (C) Incorrect. Lactation leads to a physiologic hyperplasia of the breast with increase in lobules. (D) Incorrect. A variety of vascular and parenchymal changes can occur with radiation injury. injury. (E) Incorrect. The breast is not no t a site s ite for hypoxic injury. injury.

THE END

eNotes: IVMS General Pathology Lecture Notes.pdf Notes .pdf Images: IVMS-Gross Pathology, Histopathology, Microbiology and Radiography High Yield Image Plates.pdf Plates.pdf Atlas: Klatt EC. Robbins and Cotran Atlas of Pathology 3rd Ed. Elsevier-Saunders, 2015. WebPath Website: http://www-medlib.med.ut ah.edu/WebPath/webpath.html

Textbooks: Kumar V and Abbas AK. Robbins and Cotran Pathologic Basis of Disease 8th ed. Philadelphia: Saunders, 2014.

General & Systemic Pathology Concepts_ a Global Overview

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