Pathology (phase A)

CSI - what the public thinks they do. A small part of their practice.

• Anatomical: surgical, cytology, autopsy
• Clinical: hematology, clinical chem and microbiology

disease detection by the study of individual cells

establish Who the deceased was and Where, When, and How the death occurred.

The study of blood in health and disease

An abnormal condition affecting the body (& mind) of an organism

• Reversible: can be healed, usually deals with the cytoplasm, cell adapts to fix damage (think of cell adaption slide)
• Irreversible: usually severe and long lasting problem, generally problems with the nucleus (fading, shrinking, or fragmentation)

• The plasias:
• -Hyperplasia: increased number of cells
• -Hypoplasia (aplasia): decreased (no) number of cells
• -Normoplasia: normal number of cells
• -Metaplasia: reversible change from one tissue type to another

• The trophy's:
• -atrophy: shrinking cells
• -hypertrophy: expanding cells

• -hypo/anoxia: (no oxygen) (also reoxygenation injuries)
• -toxins
• -microbial pathogens
• -physical agents
• -immunologic injury
• -genetic factors
• -nutritional factors
• -others
• -social factors

• 1) necrosis: exogenously induced
• 2) apoptosis: programmed cell death
• 3) autolysis: death of cells after death of organsim

• 1) coagulative: Proteins are coagulated like in a fried egg
• 2) Liquefactive: dissolving of tissue (pus)
• 3) caseous: cheesy necrosis, usually found in TB, dry and wet gangarene
• 4) fat: what happens when fatty tissue is injured (traumatic or enzymatic)
• 5) Fibrinoid: Looks like the deposition of on BV walls (e.g. rhematoid arthritis)

• 1) Glycogen
• 2) Proteins
• 3) Lipids
• 4) Hyaline
• 5) Lipofuscin
• 6) Pigments
• 7) Calcium

• 1) Cause
• 2) Pathogenesis
• 3) Morphological changes
• 4) clinical expression

• 1) arteriole and capp. bed dilation (increased blood flow)
• 2) increased vascular permeability (tissue edema)
• 3) Leukocytes (initially neutrophils) leave the vasculature via diapedesis migrate to site of injure (lured by chemotatic agents)
• 4) activation of leukocytes
• 5) phagocytosis, killing, and degradation of offending agent
• 6) termination: resolution, scar, chronic inflammation

• 1) heat
• 2) redness
• 3) swelling
• 4) pain
• 5) loss of function

• 1) margination and rolling along vessel wall
• 2) firm adhesion to endothelium
• 3) transmigration between endothelial cells
• 4) migration to site of infection via chemotaxis

• 1) infiltration with mononuclear cells (including macrophages, lymphocytes, and plasma cells)
• 2) tissue destruction because of inflammatory cell byproducts
• 3) repair: angiogenesis; fibrosis

• granuloma: chronic inflammation with char. aggregates of activated macrophages with scattered lymphocytes (walls off the offending agent)
• Happens in 3 settings
• 1) persistent T-cell response to certain microbes (e.g. TB, leprosy,)
• 2) Immune-mediated inflammatory disease (e.g.  Crohn's disease)
• 3) inert foreign bodies

growth of cells and tissues to replace lost structures. Requires an intact connective tissue scaffold

• labile: continuously dividing (epithelium, blood cells)
• stable: can divide if necessary (liver, kidney)
• permanent: non-dividing and peprmanently differentiated (myocytes, neurons)

• 1) tissue environment and extent of tissue damage
• 2) intensity and duration of stimulus
• 3) presence of foreign bodies or inadequate blood supply
• 4) diseases (e.g. diabetes) that inhibit repair

• 1) angiogenesis
• 2) migration and prolif. of fibroblasts
• 3) collagen synthesis
• 4) CT remodeling

• 1) vasodilation (due to VEGF and NO)
• 2) migration of endothelial cells
• 3) proliferation of endothelial cells
• 4) Inhibition of endothelial cells

1) first: knife cut, focal disruption, regeneration is the principal method of repair, 

2) second: ulcer, widespread disruption, more macrophages, heavy wound contraction, more granulation

• polymorphonuclear leukocytes (e.g. neutrophils)
• macrophages
• myofibroblasts
• fibroblasts
• angioblasts

1) dihiscence: the wound opening after suturing

2) keloid formation: accumulation of excess collagen

misfolding of proteins. The misfolded proteins cannot be degraded via the body's normal mechanisms. Can happen with any protein but often associated with SAA (becomes AA) and immunoglobulin light chains (becomes AL)

Gross: waxy pale in organs

Histo: Looks apple green when using congo red stain (specific stain used for this)

• depends on where it is located.
• heart: arrythmia, conductive disturbances, cardiomyopathy
• kidney: renal failure
• brains: role in Alzheimer's
• Diagnosis: usually an abdominal fat pad biopsy

• 1) systemic:
•  -primary: immunocyte-associated (e.g. multiple myeloma)
•  -secondary: AA-associated (e.g. chronic inflammation diseases like TB)

• 2) localized:
•  -senile cerebral: Alzheimer's disease

• 1) present in intimal layer
• 2) Chronic inflammation
• 3) multiple attempts to heal inflammation

• hypertension
• smoking
• diabetes
• hyperlipidemia

• 1) Monocytes (in the blood) enter the BV intima and become macrophages (in the tissue) because of cytokines 
• 2) These macrophages take up oxidized LDL (low density lipoprotein) and become foamy macrophages which in turn release cytokines that bring in more monocytes and bring in smooth muscle cells from the tunica media
• 3) The proliferation of these SM cells and the macrophages cause the plug to grow and release HDL over time

• 1) fatty streak: collection of foamy macrophages in the intima
• 2) fibrofatty atheroma

stable: thick fibrous cap, small lipid core, minimal inflammation

vulnerable: thin fibrous cap, large lipid core, increased inflammation

stenosis (chronic narrowing): stable angina, ischemia, small amount of flow getting through

acute plaque changes: rupture, ulceration, hemorrhage, thrombosis-embolism

Can later lead to an aneurysm (like a hernia of a blood vessel) in front of the blockage

• 1) Diagnosis
• 2) Prognosis: how will the patient do given the diagnosis?
• 3) Prediction: how will the disease respond to a specific treatment? 
• 4) Follow-up
• 5) Experimental therapy

• 1) cytopathology: fine needle aspirates; fluids
• 2) Surgical pathology: biopsies; resections
• 3) Autopsy: post-mortem organ/tissue examination

• 1) core biopsy
• 2) excision biopsy
• 3) resection

• 1) cyto and surgical specimens
•  -send fresh specimen to lab
•  -fixed for the microscope
•  -alive for flow cytometry
•  -frozen for molecular studies
•  -touch imprints for FISH
• 2) Autopsy specimens
•  -integrity depends on death-postmortem interval

a standardized template for reporting data for different sites/different centres, etc

• 1) accuracy and conveying uncertainty
• 2) turnaround time
• 3) Quality

• 1) Cause: Immediate and underlying cause
• 2) Manner: accidental, homicidal, suicidal, natural
• 3) mechanism: pathophysiologic explanations

degree to which health services increase the likelihood of desired health outcomes

• 1) Safety: avoid injuries to patients
• 2) Effective: provide services based on good science
• 3) Patient-Centred: each patient is an individual and needs to be treated with respect
• 4) Efficiency: avoid wasting resources
• 5) Equitable
• 6) Access: physical/geographic access to health facilities

• -non-random (in a recurrent pattern)
• -Circumstances and not practitioners influence errors
• -dependent on error-provoking factors in system
• -most are systemic

• 1) Organization (e.g. hierarchy) contributes to:
• 2) Environmental factors (e.g. fatigue) Contributes to:
• 3) Individual (e.g. mistakes, negligence) contributes to:
• ERROR!!!

• 1) tort culture
• 2) regulatory issues
• 3) no uniform policies
• 4) fear of peer review
• 5) ignorance of benefits

• -both are cell-derived amines
• -Histamine (mast cells, basophils, platelets)
•   -vasodilation, increased BV perm, endothelial activation
• -serotonin (platelets)
•   -vasoconstriction

• -They are cell-derived
• -both come from mast cells and leukocytes
• -prostaglandins: vasodilation, pain, fever
• -leukotrines: increased vasc perm, chemotaxis, leukocyte adhesion and activation

• -cell derived
• -come from leukocytes
• -kill microbes and cause tissue damage

• -cell-derived
• -comes from endothelium and macrophages
• -kill microbes, SM relaxation in BVs

• -cell-derived
• -.e.g. TNF, IL-1, IL-6
• -macrophages, endothelial cells, mast cells
• -local: activate endothelial cells
• -systemic: fever, shock, metabolic abnormalities (think of cytokine cascade)

• - they are plasma-derived (in the liver)
• -leukocyte chemotaxis and activation
• -Membrane attack complex
• -opsonization (mark for phagocytosis)

• - they are plasma-derived (produced in liver)
• -this group mediates vascular reaction and pain

• -they are plasma-derived (produced in liver)
• -activate clotting, endothelial activation, leukocyte recruitment

• prostaglandins
• nitric oxide
• histamine

• histamine and serotonin
• C3a and C5a
• Bradykinin
• Leukotrienes

• -TNF IL-1
• -chemokines
• -C3A, C5a
• -leukotriene
• -bacterial products

• IL-1, TNF
• Prostaglandins

• prostaglandins
• bradykinin

• ROS
• NO
• lysosomal enzymes from leukocytes