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Towards Understanding the Basic Medical Sciences Foundation of Clinical Medicine

Basic Pathology

CORRELATION TO
CORRELATION
TO

Medical Diagnosis

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

Prepared and presented by:

Marc Imhotep Cray, M.D.

The integration of basic and clinical sciences

in undergraduate medical science

IVMS teaching philosophy is based on the integration of basic and clinical sciences

This means that the learning of basic science is placed in the context of clinical medicine

Such an approach is seen to be more meaningful and relevant to medical student learning in the BMS years

Curriculum integration usually involves both horizontal and vertical integration and is the pattern that is becoming widespread throughout the world”

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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“What is

Horizontal and Vertical Integration”

Horizontal: bring together the disciplines, topics, subjects of basic medial science or clinical medicine

Vertical: bringing together basic medial science and clinical medicine

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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“Let’s exemplify vertical integration by briefly

looking at how one relates

Basic Pathology to Medical Diagnosis

PATHOLOGY
PATHOLOGY
• PATH
• PATH

pertaining to a morbid process (disease)

(from “pathos” = travail or sorrow (Greek)

• OLOGY
• OLOGY

the scientific study of …

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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PATHOLOGY: SCIENTIFIC STUDY OF…

1

ETIOLOGY

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PROGNOSIS

2

PATHOGENESIS

3

PATHO-

MORPHOLOGY

DISEASE
DISEASE

5

4

COURSE

COMPLICATIONS

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Ex: SCIENTIFIC STUDY OF DISEASE

P

E

SEPTICAEMIA

PM

ACUTE

INFLAMMATION

MENINGES

N. meningitidis

MENINGITIS
MENINGITIS

P

DEATH

(IF UNTREATED)

C

VENTRICULITIS

ENDARTERITIS

HYDROCEPHALUS

NH

SPREAD VIA CSF

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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PATHOLOGY OBJECTIVES
PATHOLOGY OBJECTIVES

1 To introduce a NEW VOCABULARY of terms, definitions, and disease processes.

NEW VOCABULARY of terms, definitions, and disease processes. 2 To introduce the BASIC RESPONSES of the

2 To introduce the BASIC RESPONSES of the human organism to injury.

Correlation with clinical picture.

to injury. • Correlation with clinical picture. “Integration of Basic Sciences and Clinical Medicine”

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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PATHOLOGY OBJECTIVE (2) STRUCTURAL & FUNCTIONAL ALTERATIONS
PATHOLOGY OBJECTIVE (2)
STRUCTURAL & FUNCTIONAL ALTERATIONS
OBJECTIVE (2) STRUCTURAL & FUNCTIONAL ALTERATIONS induced by disease CORRELATION form the basis by which

induced by disease

CORRELATION
CORRELATION

form the basis by which attending

SIGNS and SYMPTOMS
SIGNS and SYMPTOMS

are produced

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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SIGNS AND SYMPTOMS & pathologist DETECTED BY CLINICIAN PHYSIOLOGY & FUNCTION ALTERS ORGAN STRUCTURE &
SIGNS AND SYMPTOMS
SIGNS AND SYMPTOMS
SIGNS AND SYMPTOMS & pathologist DETECTED BY CLINICIAN PHYSIOLOGY & FUNCTION ALTERS ORGAN STRUCTURE &
SIGNS AND SYMPTOMS & pathologist DETECTED BY CLINICIAN PHYSIOLOGY & FUNCTION ALTERS ORGAN STRUCTURE &

& pathologist

DETECTED BY CLINICIAN

PHYSIOLOGY & FUNCTION ALTERS
PHYSIOLOGY & FUNCTION
ALTERS
ORGAN STRUCTURE
ORGAN STRUCTURE
CLINICIAN PHYSIOLOGY & FUNCTION ALTERS ORGAN STRUCTURE & clinician DETECTED BY PATHOLOGIST “Integration of
CLINICIAN PHYSIOLOGY & FUNCTION ALTERS ORGAN STRUCTURE & clinician DETECTED BY PATHOLOGIST “Integration of

& clinician

& FUNCTION ALTERS ORGAN STRUCTURE & clinician DETECTED BY PATHOLOGIST “Integration of Basic Sciences and

DETECTED BY PATHOLOGIST

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

PATHOMORPHOLOGY
PATHOMORPHOLOGY
BY PATHOLOGIST “Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D. PATHOMORPHOLOGY 9

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LEVELS OF STUDY OF PATHOLOGY
LEVELS OF STUDY OF PATHOLOGY

MOLECULAR

CHEMICAL

ULTRASTUCTURAL

CELLULAR

TISSUE

ORGAN

PATHOMORPHOLOGY
PATHOMORPHOLOGY

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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PATHOMORPHOLOGY
PATHOMORPHOLOGY

PATHO

MORPH

OLOGY

- the disease

- the shape (structure)

- the study of

i.e. how a disease process alters the “shape”

(structure) of cells, tissues and organs …… or ……

the “DAMAGE” caused by the disease process

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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“ORGANOMEGALY”
“ORGANOMEGALY”

AN ALTERATION OF MORPHOLOGY “CHANGE IN SHAPE & / 0R SIZE”

OF MORPHOLOGY “CHANGE IN SHAPE & / 0R SIZE” AS A PRECEPT THERE IS BUT ONE

AS A PRECEPT THERE IS BUT ONE

CAUSE OF ORGANOMEGALY

SOMETHING MUST BE ADDED TO THE ORGAN

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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WHAT MAY BE ADDED?
WHAT MAY BE ADDED?

NORMAL CELLS

FLUID

BLOOD

INFLAMMATORY

NEOPLASTIC CELLS

GAS

HYPERPLASIA or HYPERTROPHY

EDEMA

CONGESTION

EXUDATE

TUMOR

EMPHYSEMA

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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HISTOPATHOLOGY / PATHOMORPHOLOGY OVERVIEW
HISTOPATHOLOGY /
PATHOMORPHOLOGY OVERVIEW

Companion learning tools to the following general pathology section:

WebPath

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Cellular Degeneration and Infiltration

They are related to changes which may be reversible

The agents which cause cellular degeneration and/or infiltration , when occurring over longer periods of time, will ultimately lead to the death of the cell with morphologic changes

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Cell Injury Thus Reflects Two Levels Of Severity

1. One compatible with recovery 2. The second irreversible

1. One compatible with recovery 2. The second irreversible Morphologic changes in reversible and irreversible cell

Morphologic changes in reversible and irreversible cell injury (necrosis).

(A)

Normal kidney tubules with viable epithelial cells.

(B)

Early (reversible) ischemic injury showing surface blebs, increased eosinophilia of cytoplasm, and swelling of occasional cells.

(C)

Necrotic (irreversible) injury of epithelial cells,with loss of nuclei and fragmentation of cells and leakage of contents.

Robbins Basic Pathology 10e

COMPATIBLE WITH RECOVERY

CLASSIFICATION

Cell degeneration and infiltration can be divided into several morphologic patterns depending on metabolite(s) that accumulate in cell

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Cloudy Swelling

This is characterized morphologically by a slight swelling of the cell with granularity and cloudiness of the cytoplasm

This is seen most often in renal tubular cells, hepatic cells and cardiac muscle

Organs with this affect are slightly larger , firm and pale

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Cloudy Swelling (2)

This can be caused by many factors

Infections Febrile illness Excessive cold or heat Anoxia Malnutrition Physical injury Vascular disturbances

Hydropic or Vacuolar Degeneration

This is a more pronounced form of intracellular edema (cloudy swelling ), and although reversible , it reflects a more serious injury to cell

It is caused by same affects that produce cloudy swelling

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Hydropic or Vacuolar Degeneration (2)

This degeneration is of particular prominence in kidneys , often resulting from hypokalemia

And, in liver cells which are exposed to poisons

or toxins (such as carbon tetrachloride and

chloroform)

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Hydropic/Vacuolar Degeneration(3)

On microscopic examination this appears as

small, clear vacoules dispersed throughout

cytoplasm

In severe casesvacoules coalesce and form large clear spaces which may displace the nucleus

Progression is toward frank necrosis

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

Vacuole: A space or vesicle within cytoplasm of

a cell, enclosed by a membrane and typically containing fluid

A small cavity or space in tissue, especially in

nervous tissue as the result of disease

Fatty Deposition

(Fatty Metamorphosis)

This change is due to abnormal accumulation of fat within parenchymal cells

to abnormal accumulation of fat within parenchymal cells Reversible Cell Injury: Intracellular Accumulations. Fatty

Reversible Cell Injury: Intracellular Accumulations. Fatty liver showing large intracellular vacuoles of lipid. Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders- Elsevier, 2013.

Fatty Deposition

(Fatty Metamorphosis) (2)

Presence of fat represents an absolute increase in intracellular fat and represents severe cell injury

Size of fat vacuole is not dependent on pathologic mechanism

There are multiple causes which lead to this degeneration

Fatty change is often preceded by cloudy swelling

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Glycogen Degeneration (Infiltration)

Glycogen is normally abundant in liver and muscle cells

In some conditions abnormal accumulations occur producing visible glycogen vacoules

within cytoplasm or nuclei

Glycogen infiltration is found in

Diabetes mellitus

Glycogen storage diseases

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Hyaline Degeneration

In this form of cellular degeneration , there is a regressive change in cells in that cytoplasm now has a glassy eosinophilic appearance

This degeneration implies that injury to cell

cytoplasm has caused denaturation and coagulation of cytoplasm

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Mucoid Degeneration

This description refers to extracellular accumulation of mucopolysaccharide and ground substance within connective tissue

This change is seen in collagen diseases

There is no intra-cellular defect

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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Cell Death and Necrosis

Necrosis refers to morphologic changes that follow cell death and

permit visible recognition that cell has died

changes that follow cell death and – permit visible recognition that cell has died Marc Imhotep

IRREVERSIBLE

NECROSIS

Most of changes that indicate cellular death are more prominent in nucleus than in cytoplasm

Nuclear changes related to necrosis:

Margination of chromatin-chromatin condensing around periphery of nucleus

Chromatin clumping is reversible, but dissolution of entire nucleus is not, and when nucleus is lost, cell will die

Pyknosis–small and dense nuclei Karyolysis–complete lysis of the nuclei Karyorrhexis–fragmented nuclei (generally seen in apoptosis)

Coagulation Necrosis

This type of necrosis is characterised by cell becoming an acidophilic mass, usually with loss of nucleus, but>>>

with remnants of enough basic shape to permit recognition of cell boundaries

enough basic shape to permit recognition of cell boundaries Coagulative necrosis. (A) A wedge-shaped kidney infarct

Coagulative necrosis. (A) A wedge-shaped kidney infarct (yellow) with preservation of outlines. (B) Microscopic view of edge of the infarct, with normal kidney (N) and necrotic cells in the infarct (I). Robbins Basic Pathology 10e

Liquefaction Necrosis

In this case there is a rapid and total enzymatic dissolution of cells

There is complete destruction of cell membrane

This type of necrosis is seen often in brain

 This type of necrosis is seen often in brain Marc Imhotep Cray, M.D. Liquefactive necrosis.

Marc Imhotep Cray, M.D.

Liquefactive necrosis. An infarct in the brain shows dissolution of tissue. Robbins Basic Pathology 10e

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Enzymatic (Fat) Necrosis

This presents with acute destruction of pancreas

Results from release of pancreatic enzymes outside of their normal confines=

Action upon fat by digestive enzymes

their normal confines = Action upon fat by digestive enzymes Cellular injury to pancreatic acini leads

Cellular injury to pancreatic acini leads to release of powerful enzymes which damage fat by production of soaps, and these appear grossly as soft, chalky white areas .

https://library.med.utah.edu/WebPath/CINJHTML/CINJ026.html

Caseous Necrosis

This seen with tuberculosis infections

The cells are changed to a granular, eosinophilic mass of amorphous fat and protein

grossly looking like soft friable cheese

and protein  grossly looking like soft friable cheese Caseous necrosis. Tuberculosis of the lung, with

Caseous necrosis. Tuberculosis of the lung, with a large area of caseous necrosis containing yellow-white (cheesy) debris. Robbins Basic Pathology 10e

Gangrenous Necrosis

This is related to ischemia and a superimposed bacterial infection

initial event may have been a bacterial infection which compromised vascularity allowing saprophytic organisms to thrivethereby further increasing ischemic change

to thrive  thereby further increasing ischemic change Marc Imhotep Cray, M.D. Dry gangrene affecting the

Marc Imhotep Cray, M.D.

Dry gangrene affecting the toes as a result of peripheral artery disease. https://en.wikipedia.org/wiki/Gangrene

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Fibrinoid Necrosis

Seen principally w diseases of hypersensitivity origin

There is appearance of fibrin deposits in connective tissue and in walls of blood vessels

in connective tissue and in walls of blood vessels Marc Imhotep Cray, M.D. Fibrinoid necrosis in

Marc Imhotep Cray, M.D.

Fibrinoid necrosis in an artery in a patient with polyarteritis nodosa. The wall of the artery shows a circumferential bright pink area of necrosis with protein deposition and inflammation. Robbins Basic Pathology 10e

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Causes of Cell Injury

and Death

1) Anoxia 2) Physical Agents 3) Chemical Agents 4) Biologic Agents

5) Immune mechanisms derangements

6) Genetic Defects

“Integration of Basic Sciences and Clinical Medicine” Marc Imhotep Cray, M.D.

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DIFFERENTIAL DIAGNOSIS

VASCULAR

IS THE PROCESS
IS THE PROCESS

- SUDDEN ONSET

INFLAMMATORY

- CARDINAL SIGNS/SYMPTOMS - MASS

NEOPLASTIC

DRUGS

- HISTORY

INFECTION

- CARDINAL SIGNS/SYMPTOMS

CONGENITAL

- FROM BIRTH

AUTOIMMUNE

- SYSTEMIC

TRAUMATIC

- HISTORY

“VINDICATE

ENDOCRINE / METABOLIC

- Sn/Sx

Learn more:The Medical Database and Differential Diagnosis. pdf notes