Apoptosis and Cell Death

Fused Fingers in Newborns

• Fused fingers in a newborn can result from a failure of programmed cell death during development.

Apoptosis

• Apoptosis requires energy
• Binding of ligands to FAS and TNFR1 receptors might activate the extrinsic pathway of apoptosis

Mitochondrial (Intrinsic) Apoptotic Pathway

• Key "players" include BCL-2, cytochrome c, and Bax, Bak

Apoptosis vs. Necrosis

• Apoptotic cells do not release factors that induce inflammation
• Necrosis is involved in the formation of some organs during embryonic development

Cell Resistance Against Apoptosis

• Can be induced by stimulation of growth factors
• Can be induced by increased expression of the bcl-2 gene

Hypoxic Environment and Cell Death

• Calcium accumulation in mitochondria and the cytosol contributes most to cell swelling, chromatin clumping, and eventual cell death in a hypoxic environment.

Cellular Effects of Decreased ATP

• A decrease in cellular pH

Molecular Chaperones

• Assist in proper protein folding
• A compensatory increase in chaperone synthesis occurs in endoplasmic reticulum stress

Autophagy

• Lysosomal digestion of the cell’s own components

Ischemic Environment and Free Radicals

• Lipid peroxidation of membranes is the most direct consequence of the release of reactive oxygen species (ROS) when mitochondria are unable to maintain normal oxidative phosphorylation

Renal Dysfunction Changes

• Accumulations in glomerular mesangial areas.

Kidney Biopsy with Congo Red Stain

• Amyloid deposition

Histological Changes in Myocardium

• Coagulative necrosis

Changes in the Myocardium

• Myocardial sclerosis (scar)
• Chronic changes

Coronary Artery

• Trombosis
• Atherosclerosis
• Cholesterol accumulation

Tumor Structures

• Typical of Adenocarcinoma

Atypia Features

• Nuclear polymorphism
• Prominent nucleoli
• Increased mitotic rate

Not Features of Cytologic Atypia

• Infiltrative spread
• Distant metastasis

Local Tumor Extension

• Defined by TNM stage, which also indicates the presence/absence of metastatic disease

Malignant Tumors

• Follicular lymphoma
• Myxobrosarcoma

Noninvasive Neoplastic Process

• In situ
• Cytologic atypia

p53

• Functions as a tumor suppressor gene product

Paraneoplastic Syndrome

• May be caused by hormones released from the tumor

Cancer Cells and Aerobic Glycolysis

• Cancer cells switch to aerobic glycolysis to use intermediate metabolites of glycolysis for synthesizing cellular components

TGF-beta in Carcinogenesis

• TGFβ plays an important role in executing epithelial-mesenchymal transition program.
• In late stages of cancer development TGF-β supports invasion and metastasis

Hallmarks of Cancer

• Sustaining proliferative signaling
• Genome instability

Proto-oncogenes

• The functions identified for the proteins they express include growth factor receptors, transcription factors, cyclins and cyclin-dependent kinases, and components of signal transduction pathways
• Proto-oncogenes do not include enzymes involved in DNA mismatch repair

Ras Oncogene

• Codes for a GTPase switch protein, which in its mutated form cannot be switched off, contributing to carcinogenesis

Mechanisms of Avoiding Immune Destruction

• Polarizing macrophages towards the M1 phenotype is not a mechanism of avoiding immune destruction

Epithelial-Mesenchymal Transition

• A process involving genome instability of tumor cells

Leukocytes and Inflammation

• C5a and IL-8 are responsible for the accumulation of leukocytes at the site of injury

Acute Inflammation and Blood Vessel Permeability

• Permeability of blood vessels during an acute inflammation is increased by bradykinin and histamine

Development of Fever

• TNF-alpha and PGE2 take part in the development of fever

Consequences of Complement Activation

• Generation of opsonins
• Generation of MAC (C5b-9) and pathogen lysis
• Generation of inflammatory mediators C3a, C5a

Inflammatory Mediators and Pain

• Bradykinin and Prostaglandin E2 are inflammatory mediators likely to promote pain

Macrophage Activation

• Macrophages are activated by IL-13, IL-4 produced by T lymphocytes when TGF-beta and IL-10 are released

Acute-Phase Proteins

• Acute-phase protein synthesis is largely stimulated by IL-6
• Acute-phase proteins are mainly produced in the liver
• CRP, SAA, hepcidin, and fibrinogen are typical examples of acute-phase proteins

Leukocyte-Mediated Tissue Injury

• Macrophages don't bring damage to neighboring cells by releasing NETs

Respiratory Burst

• Free radicals are released, which have a potent microbicidal ability.

Histological Findings in Esophagus Mucosa

• Intestinal metaplasia

Stomach Biopsy

• Intestinal metaplasia is identified by the (ABPAS) histochemical stain

Barrett's Esophagus

• Intestinal metaplasia in the esophagus

Cervix Biopsy

• Dysplasia can be found in the mucosa

Liver Biopsy and Nodules

• Indicates Granuloma in males

Giant Cells

• All are foreign body type

Granulomas During Sarcoidosis and Mycobacterium Tuberculosis Infection

• Central necrosis is absent in sarcoidosis and present in tuberculosis.

Similarities Between Sarcoidosis and Tuberculosis

• Granulomas are round or oval with regular contour
• Chronic inflammation

Inflammation Activity in Mucosa

• Assessed by polymorphonuclear cells (neutrophils) in the epithelium and lamina propria of the mucosa

Nasal Cavity Polyp

• IgE hypersensitivity reaction causes edema and predominant eosinophils

Hypersensitivity Reactions

• Type III hypersensitivity is characterized by granular (IgA/IgM/C3) staining in immunofluorescence
• Electron microscopy reveals electron-dense deposits of immune complexes in type III hypersensitivity reactions
• Type II hypersensitivity is caused by auto-antibodies against antigens on cell surface or in the extracellular matrix

Correct Statements

• Abscess and phlegmona can be considered as types of suppurative inflammation
• Suppurative inflammation is predominantly polymorphonuclear (PMN) and anti-bacterial response

Intraluminal Formation

• This pulmonary artery formation is comprised of Blood elements and Fibrin

Pulmonary Artery Embolus

• The most common source is the deep veins of the legs and pelvis

Fat Embolism

• The most common site of origin is Fractures of large bones

Virchow’s Triad Factors

• Endothelial injury
• Hipercoagulative state