Basic Pathology 10th ed Robbins Kumar most recent summarized chapter one

1. Basic General Pathology
Mohammad Abusamak MD
ABO FRCSG MRCSEd (UK) FICO
Fellow Henry Ford Hospital MI USA
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2. Best Text
• Required chapters
• Ch. 1- ch. 9
• Some important
examples from
systemic pathology
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3. CELL AS A UNIT OF HEALTH AND
DISEASE
Chapter ONE
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4. OBJECTIVES
 CELL –
GENOME,
PLASMA MEMBRANE,
ORGANELLES,
CELLULAR ACTIVATION,
EXTRACELLULAR MATRIX,
CELL DIVISION,
STEM CELLS
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5. CELL
 Pathology – patho – suffering, logos –
study
 Cellular pathology – Virchow – study
of cellular abnormalities
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6. GENOME
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7. GENOME
 Human genome contain roughly 3.2 billion
DNA base pairs, only 1.5% (20,000) of which
code for proteins (coding genes), remaining
are non coding genes
 This coding genome is similar across
species, and the diversity lies in the non
coding genome
 As the complexity of organism increases so
does the proportion of non coding genome
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10. WE ARE 99.9%
SIMILAR
 ANY TWO INDIVIDUALS –
99.9
 HUMAN AND CHIMPS –
99.5
 HUMAN AND CAT - 90
 HUMAN AND CHICKEN –
60
 DIFFERENCE IS DUE TO
VARIATIONS IN
GENOMES CALLED
SNP – SINGLE NUCLEOTIDE
POLYMORPHISM
CNV – COPY NUMBER
VARIATION
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11. EPIGENETICS
 Even though virtually all cells in the body contain the
same genetic material, terminally differentiated cells have
distinct structures and functions.
 Clearly, different cell types are distinguished by
lineage-specific programs of gene expression and not by
genetic differences
 Study of such cell type-specific differences in DNA
transcription and translation is
known as EPIGENETICS
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12. EPIGENETICS
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13. EPIGENETIC FACTORS
 HISTONES
 DNA in cell is wound around these
proteins
 Not uniformly wound – Heterochromatin
and Euchromatin
 Histone acetylation and methylation can
cause neoplasia
 NON CODING RNAs – microRNAs and
longRNAs
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14. miRNA
• Primarily involved in gene silencing, if doesn’t
work, can lead to neoplasia.
• That means it’s a tumor suppressor
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15. miRNA
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16. Long non coding RNA (lncRNA)
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17. ORGANELLES
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18. ORGANELLES
 PLASMA MEMBRANE
 GOLGI BODIES AND ENDOPLASMIC
RETICULUM
 LYSOSOMES
 MITOCHONDRIA
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19. ORGANELLES
 PLASMA MEMBRANE
 GOLGI BODIES AND
ENDOPLASMIC RETICULUM
 LYSOSOMES
 MITOCHONDRIA
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20. CELLULAR HOUSEKEEPING
A cell can survive only if the following
house keeping functions are performed
on a regular basis
protection from the environment,
nutrient acquisition,
communication,
movement,
renewal of senescent molecules,
Molecular catabolism,
energy generation
.
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21. 1. PLASMA MEMBRANE
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22. Functions of plasma
membrane
 (1) ion and metabolite transport
 (2) fluid-phase and receptor mediated
uptake of macromolecules, and
 (3) cell-ligand, cell-matrix, and cell-
cell interactions.
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23. Passive diffusion
Active transport
Oxygen
Carbondioxide
Steroid based –
estradiol, Vit D
Water Ethanol
Urea
transferrin and
low-density
lipoprotein (LDL)
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25. 2. CYTOSKELETON
 The ability of cells to adopt a particular
shape,
 Maintain polarity, organize the relationship
of intracellular organelles, and move about
Depends on the intracellular scaffolding of
proteins called the cytoskeleton
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26. 2. CYTOSKELETON
 The ability of cells to adopt a particular shape,
 Maintain polarity,
 organize the relationship of intracellular
organelles,
 and move about
Depends on the intracellular scaffolding of proteins
called the cytoskeleton
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27. 3. ENDOPLASMIC RETICULUM
GOLGI APPARATUS
(Biosynthetic Machinery)
 The structural proteins and enzymes of the
cell are constantly renewed by ongoing
synthesis tightly balanced with intracellular
degradation.
 The endoplasmic reticulum (ER) is the site for
synthesis of all the transmembrane proteins and
lipids for plasma membrane and cellular organelles,
including ER itself.
 It is also the initial site for the synthesis of all
molecules destined for export out of the cell.
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29. 4. LYSOSOMES AND PROTEASOMES
 Lysosomes are membrane-bound
organelles containing roughly 40 different acid
hydrolases
 Functions
 Autophagy – senescent organelles
 Heterophagy (Macrophages and leucocytes) –
destroy pathogens
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30. 4. LYSOSOMES AND PROTEASOMES
 Lysosomes are membrane-bound organelles containing
roughly 40 different acid hydrolases
 Functions
 Autophagy – senescent organelles
 Heterophagy (Macrophages and leucocytes) – destroy pathogens
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31. PROTEASOMES
 Proteasomes play an important role in degrading
cytosolic proteins these include denatured or misfolded
proteins
 any other macromolecule whose lifespan needs to be
regulated (e.g., transcription factors)
 Proteasomes digest proteins into small (6 to 12 amino
acids) fragments that can subsequently be degraded to
their constituent amino acids and recycled.
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32. PROTEASOMES
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33. 5. MITOCHONDRIA
 Mitochondria provide the enzymatic machinery for oxidative
phosphorylation (and thus the relatively efficient generation
of energy from glucose and fatty acid substrates).
 They also play a fundamental role in regulating programmed
cell death, so-called
apoptosis
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34. CELLULAR
COMMUNICATION
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35. CELLULAR COMMUNICATION
 Extra cellular communication - extracellular
signals determine whether a cell lives or dies, or
whether it remains quiescent or is stimulated to
perform its specific function.
 Intercellular signaling –
 clearly important in the developing embryo, that
tissues respond in an adaptive and effective fashion to
various threats, such as local tissue trauma or a systemic
infection.
Loss of cellular communication can variously lead
to growth (cancer) or an ineffective response to
extrinsic stress (as in shock).
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36. Stages of cellular communication
1. Signalling
2. Signal Transduction
3. Cellular activation or deactivation
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37. Stages of cellular communication
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38. SIGNAL TRANSDUCTION
 Binding of a ligand to a cell surface receptor
mediates signaling
 Cellular receptors are grouped into several types
based on the signaling mechanisms
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39. CELLULAR ACTIVATION
(/DEACTIVATION)
 Enzyme activation (or inactivation)
 Transcription factor activation (or inactivation)
 Most signal transduction pathways ultimately
influence cellular function by modulating gene
transcription
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40. GROWTH FACTORS
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41. GROWTH FACTORS
 role of growth factors
is to stimulate the
activity of genes that
are required for cell
growth and cell
division
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43. EXTRACELLULAR MATRIX
 Extracellular matrix (ECM) is a network of interstitial proteins
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44. EXTRACELLULAR
MATRIX
 Extracellular matrix (ECM) is a network of interstitial proteins
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45. CELL CYCLE
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46. CELL
CYCLE
 The sequence of
events that results in
cell division is called
the cell cycle
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47. CELL CYCLE contd.
 The cell cycle is regulated by activators and
inhibitors.
 Cell cycle progression is driven by proteins
called cyclins and cyclin-associated enzyme called
cyclin dependent kinases (CDKs)
 Enforcing the cell cycle checkpoints is the job of
CDK inhibitors (CDKIs)
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48. CELL CYCLE contd.
 The cell cycle is regulated by activators and
inhibitors.
 Cell cycle progression is driven by proteins called
cyclins and cyclin-associated enzyme called cyclin dependent
kinases (CDKs)
 Enforcing the cell cycle checkpoints is the job of
CDK inhibitors (CDKIs)
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49. STEM CELLS
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50. STEM CELLS
 During development, stem cells give rise
to all the various differentiated tissues
 In the adult organism, stem cells
replace damaged or senescent cells
 Stem cells are characterized by two
important
properties:
 Self-renewal, which permits stem cells to
maintain their numbers.
 Asymmetric division, in which one daughter cell
enters a differentiation pathway and gives
rise to mature cells, while the other remains
undifferentiated and retains its self-renewal
capacity.
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51. Types of stem cells
 Embryonic stem cells - Totipotent
 Adult stem cells
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52. Types of stem cells
 Embryonic stem cells -
Totipotent
 Adult stem cells
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53. Hematopoietic stem cells
 Hematopoietic stem cells may be isolated directly from bone
marrow, as well as from the peripheral blood
 These stem cells can be used to repopulate marrows depleted
after chemotherapy (e.g., for leukaemia), or to provide normal
precursors to correct various blood cell defects e.g. sickle cell
disease
 Besides hematopoietic stem cells, the bone marrow (and
notably, other tissues such as fat) also contains a population of
mesenchymal stem cells. These are multipotent cells that can
differentiate into a variety of stromal cells including chondrocytes
(cartilage), osteocytes (bone), adipocytes (fat), and myocytes
(muscle).
 they may represent a ready means of manufacturing the stromal cellular
scaffolding for tissue regeneration.
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54. Regenerative
medicine
 identify, isolate, expand, and
transplant stem cells
 a handful of genes have been
identified whose products can
—remarkably—reprogram
somatic cells to achieve the
“stem-ness” of ES cells
 Eg. insulin-secreting β-cells in
a patient with diabetes
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55. Summary
• CELL – GENOME, PLASMA MEMBRANE,
ORGANELLES, CELLULAR ACTIVATION,
EXTRACELLULAR MATRIX, CELL DIVISION,STEM
CELLS
• This survey of selected topics in cell biology will
serve as a basis for our later discussions of
pathology and we will refer back to it throughout
the book
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