Professional Documents
Culture Documents
Pathoma Notes CH 1-3
Pathoma Notes CH 1-3
hypertrophy +
stress = cell size
hyperplasia
involves gene activation + protein synthesis + production of
generally occur
organelles
together
*PERMANENT TISSUES = HYPERTROPHY ONLY
(cannot make new cells):
Ex: uterus during
(1) Cardiac Muscle (LV Hypertrophy due to systemic HTN)
pregnancy
(2) Skeletal Muscle
LV Hypertrophy
1st = hyperplasia
(3) Nerve
of smooth muscle
stress = # of cells
2nd = hypertrophy
involves production of new cells from stem cells
of smooth muscle
Physiologic Hyperplasia = does NOT risk of cancer
HYPERPLASIA Pathologic Hyperplasia = risk of cancer
Pathologic Hyperplasia Dysplasia Cancer
ex: Endometrial Hyperplasia
*EXCEPTION: Benign Prostatic Hyperplasia = no risk of cancer
stress = cell size + # of cells
ex: hormonal stimulation, disuse or nutrients/blood supply
ATROPHY
Apoptosis = # of cells
Ubiquitin-proteosome degradation (intermediate filaments of cytoskeleton destroyed) +
Autophagy (autophagic vacuoles fuse w/ lysosomes) = cell size
METAPLASIA
stress = cell type
involves surface epithelium:
Squamous (keratinizing or non-keratinizing)
squamous
Columnar (gut)
Urothelial (transitional)
columnar
occurs via reprogramming of stem cells which then produce new cell type
*REVERSIBLE (ex: tx of GERD)
Barrett Esophagus persistent stress Metaplasia Dysplasia Cancer
(ex: Barrett Esophagus Adenocarcinoma of Esophagus)
*EXCEPTION: Apocrine Metaplasia of Breast = no risk of cancer
Barrett esophagus
non-keratinizing squamous epithelium non-ciliated, mucin-producing columnar cells =
contains goblet cells
Keratomalacia
due to GERD
Keratomalacia = Vitamin A deficiency Metaplasia (or night blindness, PML)
Myositis Ossificans Vit A = necessary for differentiation of conjunctiva
thin squamous lining of conjunctiva thick stratified keratinizing squamous epithelium
Myositis Ossificans = Mesenchymal (connective) tissue Metaplasia
trauma to skeletal muscle inflammation metaplasia bone
NOT Osteosarcoma because bony growth is in muscle NOT coming off of bone
disordered cellular growth = proliferation of precancerous cells
Cervical Intraepithelial Neoplasia (CIN) = dysplasia = precursor to cervical cancer
DYSPLASIA
arise from longstanding pathologic hyperplasia (Endometrial Hyperplasia) or metaplasia
(Barrett Esophagus)
*REVERSIBLE
persistent stress Dysplasia Cancer (= IRREVERSIBLE)
APLASIA
failure of cell production during embryogenesis
Unilateral Renal Agenesis = failure to produce 1 kidney during embryogenesis
HYPOPLASIA
cell production during embryogenesis = small organ
Streak Ovary during Turner Syndrome
HYPERTROPY
REVERSIBLE INJURY
(1)
(2)
(3)
IRREVERSIBLE INJURY
due to persistent injury
*HALLMARK = MEMBRANE DAMAGE
(1) plasma membrane damage
cytosolic enzymes leak into serum (ex: troponin)
[Ca2+] entering cell
(2) mitochondrial membrane damage
loss of ETC (= inner mitochondrial membrane)
cytochrome C leaks into cytosol (activates
apoptosis)
(3) lysosome membrane
hydrolytic enzymes leak into cytosol = activated
by [Ca2+] intracellularly
end result = death
NECROSIS = murder
death of large group of cells followed by ACUTE INFLAMMATION
due to underlying pathologic process
COAGULATIVE NECROSIS
necrotic tissue
= firm
nuclei
disappear
normal
tissue
Red
Infarction
DYSTROPHIC CALCIFICATION
NORMAL serum [Ca2+] + [PO4]
calcification occurs in necrotic tissue = nidus
ex: psammoma bodies in:
Papillary Thyroid Carcinoma
Meningioma
Papillary Serous Carcinoma of Ovary
METASTATIC CALCIFICATION
HIGH serum [Ca2+] or [PO4]
calcification occurs in normal tissue
ex: Hyperparathyroidism = nephrocalcinosis
ex: Bone Metastatic Cancer = metastatic calcification
AMYLOIDOSIS
amyloid = misfolded protein deposits in extracellular space = tissue damage
common characteristics:
pleated sheet
congo red stain
apple-green bifringence
amyloid deposits in multiple body systems
Primary Amyloidosis
systemic deposition of AL amyloid = derived from Ig light chain
ex: Multiple Myeloma = plasma cell dyscrasias = abnormalities of plasma
cell = over production of Ig light chain leaks out into blood misfolds
deposits into tissues
Secondary Amyloidosis
systemic deposition of AA amyloid = derived from SAA = serum
associated amyloid
SAA in:
chronic inflammatory states
malignancy
Familial Mediterranean Fever (FMF) = dysfunction of neutrophils
SYSTEMIC AMYLOIDOSIS
neutrophils activate + create attack = acute inflammation
fever + acute serosal inflammation
can mimic MI = serosal surface of heart or acute
appendicitis = serosal surface of abdomen
acute inflammation = SAA = AA = secondary amyloidosis
Classical findings:
*KIDNEY = most common organ
Nephrotic Syndrome
Restrictive Cardiomyopathy or arrhythmia = compliance no filling =
cardiac failure
tongue enlargement, bowel-wall thickening (malabsorption)
Hepatosplenomegaly
Diagnosis:
biopsy of abdominal fat pad + rectum mucosa = easy targets
*AMYLOID CANNOT BE REMOVED = damaged organ must be transplanted
amyloid deposits localized to single organ system
Senile Cardiac Amyloidosis
amyloid = serum transthyretin deposits in heart
asymptomatic 25% of people > 80 yo
Familial Amyloid Cardiomyopathy
amyloid = mutated serum transthyretin deposits in heart
leads to restrictive cardiomyopathy heart = compliance no filling =
cardiac failure
5% african americans carry mutated gene
Type II Diabetes Mellitus (insulin resistance = insulin production)
LOCALIZED AMYLOIDOSIS
amyloid = amylin (derived from insulin) deposits in islets of pancreas
Alzheimer Disease
amyloid = A amyloid = deposits in brain
plaque in brain (derived from amyloid precursor on protein = gene on
chromosome 21 pts w/ Down Syndrome develop early onset alzheimer)
Dialysis-associated Amyloidosis
amyloid = 2-microglobulin = deposits in joints
Medullary Carcinoma of Thyroid
amyloid = calcitonin = deposits in tumour = tumour cells in amyloid
background
tumor of thyroid derived from c-cells = produce calcitonin
INFLAMMATION
inflammatory cells + plasma cells + fluid exit BV + enter interstitial space
*NEUTROPHILS = ACUTE INFLAMMATION
*LYMPHOCYTES = CHRONIC INFLAMMATION
acute inflammation
w/ neutrophils
chronic inflammation
w/ lymphocyte +
plasma cells
(D) Complement
STEP 1
Margination
(1)
(2)
(1)
STEP 2
Rolling
(2)
(3)
(1)
STEP 3
Adhesion
STEP 4
Transmigration +
Chemotaxis
(2)
(3)
(4)
(1)
(2)
(1)
(2)
STEP 5
Phagocytosis
(3)
(1)
(2)
(3)
STEP 6
Destruction of
Phagocytosed Material
(4)
(5)
STEP 7: Resolution
(1)
REDNESS (RUBOR)
+
WARMTH (CALOR)
SWELLING
(TUMOR)
PAIN (DOLOR)
FEVER
(4) MACROPHAGES
CHRONIC INFLAMMATION
LYMPHOCYTES + PLASMA CELLS
delayed response + more specific (ADAPTIVE IMMUNITY) than acute inflammation
Stimuli:
persistent infection = MOST COMMON CAUSE
infection w/ viruses + mycobacteria + parasites + fungi
autoimmune diseases
foreign material
some cancers
produced in bone marrow as progenitor T cells
develop in thymus where T-cell receptor (TCR) undergoes rearrangement + progenitor
cells become CD4+ helper T cells OR CD8+ cytotoxic T cells
(1) T cells use TCR complex = TCR + CD3 for antigen surveillance
(2) TCR complex recognizes antigen presented on MHC molecules
CD4+ cells MHC class II, CD8+ cells MHC class I
(3) activation of T cells requires: binding of antigen/MHC complex + additional 2nd signal
CD4+ helper T cell activation:
(1) extracellular antigen (ex: foreign protein) phagocytosed + processed +
presented on MHC II = expressed by antigen presenting cells (APCs)
(2) B7 on APC binds CD28 on CD4+ helper T cells providing 2nd activation signal
(3) Activated CD4+ helper T cells secrete cytokines = help inflammation + divided
into 2 subsets:
(A) T LYMPHOCYTES
(1) TH1 subset secretes IL-2 (T cell growth factor + CD8+ T cell activator)
+ TFN- (macrophage activator)
(2) TH2 subset secretes IL-4 (facilitates B-cell class switching to IgG + IgE)
+ IL-5 (eosinophil chemotaxis +
CD8+ cytotoxic T cell activation:
(1) intracellular antigen (derived from proteins in cytoplasm) processed +
presented on MHC I = expressed by all nucleated cells + platelets
(2) IL-2 from CD4+ TH1 cells provides 2nd activation signal
(3) Cytotoxic T cells are activated for killing
(4) Killing occurs via:
secretion of perforin + granzyme apoptosis
expression of FasL which binds Fas on target cells apoptosis
immature B cells produced in bone marrow + undergo Ig rearrangements to
become naive B cells that express surface IgM + IgD
B-cell activation occurs via:
(1) Antigen binding by surface IgM or IgD = maturation to IgM- or IdD-secreting
(B) B LYMPHOCYTES
plasma cells
(2) B-cell antigen presentation to CD4+ helper T cells via MHC II
CD40 receptor on B cell binds CD40L on helper T cells via MHC II
providing 2nd activation signal
Helper T cell secretes IL-4 + IL-5 (mediates B-cell isotype switching +
hypermutation + maturation to plasma cells)
(C) GRANULOMATOUS subtype of chronic inflammation
characterized by granuloma = collection of epithelioid histiocytes (macrophages w/
INFLAMMATION
abundant pink cytoplasm) = surrounded by giant cells + rim of lymphocytes
divided into noncaseating + caseating subtypes:
(A) NONCASEATING GRANULOMAS = lack central necrosis + etiologies = rxn to
foreign material + sarcoidosis + beryllium exposure + Crohn disease + cat scratch
disease
(B) CASEATING GRANULOMAS = exhibit central necrosis + characteristic of
tuberculosis + fungal infections
steps involved in granuloma formation:
(1) macrophages process + present antigen via MHC II to CD4+ helper T cells
(2) macrophages secrete IL-12 inducing CD4+ helper T cells to differentiate into TH1 cells
(3) TH1 cells secrete TFN- = converts macrophages to epithelioid histiocytes + giant cells