GEN PATHO REVIEW OF THE CELL PDF

REVIEW OF THE CELL Centrioles CELL INCLUSION BODIES Basic structural and functional unit of life Lifeless accumulations of metabolites, The smallest unit that can live on its own cellular...

REVIEW OF THE CELL Centrioles CELL INCLUSION BODIES Basic structural and functional unit of life Lifeless accumulations of metabolites, The smallest unit that can live on its own cellular products and secretions and that makes up all living organisms and Ex: Pigments (melanin, carotene), glycogen the tissues of the body vacuoles, lipid vacuoles THE CELL THEORY Mitochondria: ATP synthesis, has a role in Schleiden and Schwann Cell Theory apoptosis 1. All living things are made up of cells Lysosomes: intracellular digestion and turnover 2. Cells are potentially independent organisms of cellular components capable of independent existence Rough endoplasmic reticulum (RER): protein 3. Cells emerge from preexisting cells by cell synthesis division Smooth endoplasmic reticulum (SER): phospholipid and steroid synthesis; calcium HISTOPATHOLOGY release and sequestration - Proposed by Rudolf Virchow (Father of Golgi apparatus: packages proteins into Modern Pathology) membrane-bound vesicles Disease can be explained by alterations in the Proteasomes: degrade nonfunctional and structure and function of the cell denatured proteins Cells are in homeostasis with the extracellular Peroxisomes: H202 production and degradation fluid and respond to changes in their environment and detoxification Nucleus: found in all cells except RBCs and COMPARTMENTS OF THE CELL keratinocytes; contains chromosomes Nuclear envelope: contains pores which Cytoplasm/Cytosol allows movement of hereditary material in and out Enclosed by the cell membrane of the nucleus Where cell organelles and inclusion Nucleoplasm: where the chromosomes are bodies are suspended suspended Site of synthesis and metabolism Ribosomes: assemble polypeptides and proteins Microtubules: help move cells; intracellular Karyoplasm/Nucleoplasm transport Enclosed by the nuclear membrane Microfilaments: structure and support in the cell Where chromosomes are suspended ; separates cells during cell division Intermediate filament: structural stability and ORGANELLES MEMBRANE-BOUND strength Mitochondria Centrioles: organizes microtubules Lysosome Endoplasmic reticulum TISSUES Golgi apparatus A group of cells that have similar structure Peroxisomes and that function together as a unit Proteasomes Nucleus TYPES OF TISSUES EPITHELIAL - Covers body surfaces, lines hollow organs, body cavities and ducts, and forms NON-MEMBRANE-BOUND glands Ribosomes Microtubules CONNECTIVE - Protects and supports the body Microfilaments and its organs, binds organs together, stores Intermediate filaments energy reserves, provides immunity 1  Surface of ovary MUSCLE - Movement and generation of force NERVOUS - Initiates and transmits action potentials to coordinate body activities Epithelial tissues GENERAL DESCRIPTION Avascular Layers of contiguous cells covering an external SIMPLE COLUMNAR surface or lining an internal cavity - Rectangular outlines with nuclei aligned at All epithelial cells rest on a basement membrane the same level Functions: Locations: Protective covering (ex: skin epithelium) Digestive tract (lining of small intestine, Absorption (ex: intestinal epithelium) stomach) Secretion (ex: glandular epithelium) Ciliated: pulmonary bronchi Contractility (ex: myoepithelial cells) CLASSIFICATION SHAPE OF EPITHELIAL CELLS Squamous: flat Cuboidal: square Columnar: rectangular NUMBER OF CELL LAYERS Simple epithelium: single layer of cells Stratified epithelium: 2 or more layers STRATIFIED SQUAMOUS - Keratinized stratified squamous: lines the surface of the body Ex: epidermis of the skin - Non-keratinizing stratified squamous: lines unexposed sites of the body Ex: oral cavity, epiglottis, esophagus SIMPLE SQUAMOUS - Top view: tile-like pattern - Side view: thin and fusiform Locations: Pulmonary alveoli Endothelium Parietal layer of Bowman’s capsule STRATIFIED CUBOIDAL - Uncommon - Typically seen in exocrine glands SIMPLE CUBOIDAL Location: - Top view: mosaic of polygonal tiles Ducts of sweat glands - Side view: box-like cubes Locations: Thyroid follicles 2  Mature Connective Tissue Loose Dense (Dense Regular & Dense Irregular) Special Connective Tissue Reticular Adipose PSEUDOSTRATIFIED COLUMNAR Cartilage EPITHELIUM Bone - Nuclei are aligned at 2 levels or more Blood creating an illusion of stratification - True simple epithelia Others Location: Fibrous Primary bronchi Elastic Trachea Lymphoid Auditory tube LOOSE CONNECTIVE TISSUE Most common type of connective tissue Holds organs in place and attaches epithelial tissues to its underlying layers TRANSITIONAL EPITHELIUM - Found only in the urinary tract - Adjusts to emptying and filling of urinary bladder - On emptying: Superficial cells are large and rounded - On filling: Contains 3 types of fibers: Superficial cells are flattened out Collagen fibers: for support and attachment, binds bones and tissues to one another Elastic fibers: allow organs such as blood vessels and lungs to recoil Reticular fibers: consists of one or more type of collagen fibers to form a scaffolding for other cells; seen in bone Connective tissues marrow GENERAL DESCRIPTION Tissues that connect, support, bind, or DENSE CONNECTIVE TISSUE separate other tissues or organs Main matrix element: fibers that are tightly One of the four basic types of tissues adherent to one another along with epithelial tissue, muscle tissue, Mainly composed of type I collagen and nervous tissue Develops from the mesoderm Composed of three components: fibers, ground substance, cells CLASSIFICATION 3  Fibrocartilage: intervertebral disc Subtypes: Dense Regular: bundled in a parallel fashion; seen in tendons, ligaments, fascia Dense Irregular: fibers are randomly arranged; seen in digestive tract, periosteum BONE A metabolically active tissue composed of several types of cells RETICULAR CONNECTIVE TISSUE Osteoblasts: creation and mineralization Network of reticular fibers, made of type of bone tissue III collagen Osteocytes: small mature cells on the Reticular fibers: thin branching structures dense connective tissue part of the bone synthesized by special fibroblasts called Osteoclasts: large immature cells reticular cells embedded on the loose connective tissue Located in the kidney, spleen, lymph part of the bone nodes, bone marrow BLOOD Delivers necessary substances such as nutrients and oxygen to the cells Transports metabolic waste products Accounts to 7% of the human body weight Average adult blood volume: 5-6 liters ADIPOSE CONNECTIVE TISSUE Composed of fat cells called adipocytes Main role: storage of energy in the form of lipids Cushions and insulates the body ELASTIC Consists predominantly of fibroblasts and freely branching elastic fibers Allows stretching of certain tissues like the elastic arteries (aorta) CARTILAGE CONNECTIVE TISSUE Rubber-like padding that covers and protects the ends of long bones at joints Synthesized by chondrocytes 3 types: Elastic cartilage: outer ear Hyaline cartilage: articular surface of bones 4 Muscle tissues FUNCTIONS - Body movements - Stabilizes body position - Heat generation and energy Properties: Electrical excitability Contractility Extensibility Elasticity Types: Divisions of pathology Skeletal muscle: produce quick forceful GENERAL PATHOLOGY - Common reactions of contractions that are voluntary. (Striated, cells and tissues to injurious stimuli voluntary) SYSTEMIC PATHOLOGY - Alterations and underlying mechanisms in organ-specific diseases Core of pathology Cardiac muscle: produce a characteristics wave 1. Etiology - refers to the cause of the contraction in the heart. (Striated, involuntary) damage/injury Intrinsic: Present at birth Inherited mutations, disease-associated gene variants Aquired: Factors present in the environment which Smooth muscle: produce slow, steady present as injurious stimuli involuntary contractions. (Non-striated, involuntary) 2. Pathogenesis - Refers to the mechanisms of the development of the disease. From the time of exposure to the initial stimulus to the ultimate expression of the disease 3. Morphologic changes - refers to the structural alterations in cells or tissues Introduction to pathology Pathology “PATHOS diseases “LOGOS” study - Study of the structural, biochemical, and functional changes in cells, tissues, and 4. Clinical significance - Functional organs that underlie disease consequences/derangement of the disease. End results of changes in cells and tissues that cause functional abnormalities Clinical features (signs and symptoms) 5 Cellular adaptations: Hyperplasia, hypertrophy, atrophy, metaplasia homeostasis Balance maintained when stress or an injurious stimuli is relieved Basis for adaptation of cell MECHANISMS: Adaptive responses Genes induced Reversible changes ○ Transcription factors which results in increased protein synthesis INCREASE IN CELLULAR ACTIVITY ○ Growth factors (TGF-B, IGF1, Hypertrophy FGF) Increase in cell size ○ Vasoactive agents (facilitates No new cells are formed because the cells signaling between cells and are incapable of cell division tissues) Happens in non-dividing cells Switch of contractile proteins from fetal to Mechanism is by synthesis of structural adult forms components Reinduction of ANP (atrial natriuretic Can be physiologic or pathologic peptide) ○ Associated with cardiac hypertrophy Hyperplasia Increase in the number of cells in an organ or tissue Happens in cells capable of DNA normal PHYSIOLOGIC: cells synthesis; or those with abundant Increased functional demand tissue stem cells Example: skeletal muscle in weightlifters, End result: increase in the volume of gravid uterus organ or tissue (lalaki yung organ) Can be physiologic or pathologic PHYSIOLOGIC: Hormonal Hyperplasia Influenced by the physiologic increase in concentration of hormone resulting in increased functional capacity Hyperplasia of female breast and uterus PATHOLOGIC: during pregnancy Compensatory adaptation due to Comparison: non lactating— abundance increased workload stroma Example: Cardiac hypertrophy (left ventricular hypertrophy- loss its property to be contractile) due to Chronic systemic hypertension 6  DECREASE IN CELLULAR ACTIVITY Atrophy Shrinkage in the size of the cells by loss of cell substance Decrease in the size of tissue Can be physiologic or pathologic Physiologic atrophy seen in uterus, ovaries, and fallopian tubes (menopause), Compensatory Hyperplasia breast (decreased estrogen) Increased tissue mass after damage/partial resection to compensate for loss of tissue Kidneys and liver that regenerate after resection Pathologic atrophy: Decreased workload (atrophy of disuse) ○ Loss of innervation ○ Ischemia (no blood supply) ○ Inadequate nutrition ○ Loss of endocrine stimulation ○ Aging PATHOLOGIC: Take place in the presence of excessive hormonal stimulation/growth factors acting on target cells Regression happens when hormonal ⬇️ stimulation is withdrawn MECHANISMS: May be a risk factor to cancer proliferation Decreased protein synthesis because Benign prostatic hyperplasia (common of reduced metabolic activity- hindi ⬆️ in elderly male), endometrial hyperplasia ginagamit yung organ Increased protein degradation by lysosomes (intracellular digestion), ⬆️ hormones, cytokines Increase in the number of autophagic vacuoles (eating cellular components) Autophagy: the mechanism by which the starved cell eats its own components in an attempt to reduce nutrient demand to match the supply; self-eating MECHANISM: ALTERATION OF CELL MORPHOLOGY Increased local production of growth Metaplasia factors One adult cell type is replaced by another Increased levels of growth factor receptors cell type on responding cells The cells need to transform to a sturdier Activation of intracellular signaling type to withstand stress pathways that favors cell division One cell type that is sensitive to a Stem cell stimulation (precursor) particular stress is replaced by another 7  cell type that is better able to withstand Occurs in tissues capable of cell division the adverse environment or contain abundant tissue stem cells Most common epithelial metaplasia: columnar to squamous (chronic irritation ATROPHY from smoke) Decreased cell and organ size Due to decreased nutrient supply or disuse Associated with decreased synthesis of cellular building blocks and increased breakdown of cellular organelles METAPLASIA Change in phenotype of differentiated cells Usually induced by altered differentiation Although the epithelial lining becomes pathway of tissue stem cells tough, important mechanisms of protection May result in reduced functions or (such as mucus production) against increased propensity for malignancy infection are lost Can predispose to malignancy Squamous to columnar metaplasia ○ Barrett esophagus ○ Esophageal squamous epithelium is replaced by intestinal-like columnar cells under the influence of refluxed gastric acid ○ Precursor to developing cancer INTRACELLULAR ACCUMULATIONS AN OVERVIEW MECHANISMS 1. INADEQUATE REMOVAL A normal endogenous substance is produced at a normal rate MECHANISMS: The rate of metabolism is inadequate to Reprogramming of stem cells remove it Transcription factor dysregulation It accumulates within the cytoplasm of the cell Recall: Example: HYPERTROPHY Fatty change in the liver Increased cell and organ size Reabsorption protein droplets in In response to increased workload the tubules of the kidney Occurs in tissues incapable of cell division HYPERPLASIA Increased cell number In response to hormones and growth factors 8 2. DEFECTS IN PROTEIN FOLDING AND TRANSPORT An abnormal endogenous substance accumulates due to: ○ Defects in protein folding and transport ○ Inability to degrade the abnormal protein efficiently Example: INTRACELLULAR ACCUMULATIONS ○ Mutated al-antitrypsin in liver cells LIPID ACCUMULATIONS ○ Degenerative disorders of the 1. STEATOSIS CNS Also called fatty change or fatty degeneration Abnormal accumulations of triglycerides within parenchymal cells Organs affected: Liver- main example— fat metabolism (triglycerides) Muscle 3. ENZYME DEFICIENCIES Heart A normal endogenous substance Kidney accumulated because of ○ Defects in enzymes required for the metabolism of the substance Example: ○ Lysosomal (degradation of intracellular organelles) storage diseases —reversible 4. ACCUMULATION OF ABNORMAL Fatty - you depositing triglycerides in the EXOGENOUS SUBSTANCES parenchymal liver Exogenous - coming from the outside Fibrosis- deposition of fibrous tissue An abnormal exogenous substance is deposited and accumulated because the —-irreversible cell has neither: Cirrhosis - permanent scarring of liver tissue ○ Enzymatic machinery to degrade Cancer - hepatocellular carcinoma- high mortility the substance ○ Ability to transport it to other Sites Causes of Steatosis/fatty liver Example: cold Alcohol (most common in developing nations) Obesity (most common in developed nations) Toxins Protein malnutrition Diabetes mellitus Obesity Anorexia 9  Alcoholic Fatty Liver Disease The alcohol is catalyzed by the enzyme Type 2 Diabetes mellitus called alcohol dehydrogenase, in the Intake of food - release enzyme insulin process there is coenzyme called NAD+ (lower the glucose level) will be reduce to NADH—less production Insulin resistance - cause the — adipocyte of NAD+ and increase NADH end product dysfunction — decrease adiponectin — = acetaldehyde (toxic metabolite, increase in free fatty acid hepatotoxic- toxic to liver cells) The decrease in NAD+ there is less fatty Normal Liver vs Fatty Liver acid oxidation — deposition of triglyceride Upon the generation of acetaldehyde you also produce reactive oxygen species (substances that are harmful to your proteins and DNA)- Hydrogen peroxide, hydroxyl radical, superoxide anion Acetaldehyde it has the tendency to stick or bind to macromolecules that can become antigenic (it can be recognize as kalaban) The immune system would now recognize this as foreign substance so it will be attacked 10 Cross section : discoloration Cholesterol cleft- are actually done by tissue processing 2. CHOLESTEROL AND CHOLESTEROL ESTERS Intracellular vacuoles macrophages Presence of foamy macrophages Gross appearance: Yellow, soft to firm substance - passing in tunica media ATHEROSCLEROSIS XANTHOMA Vascular disease Cutaneous depositions of cholesterol Affects medium arteries to large-size Painless Progresses the lumen of the blood vessel that will be obliterated by plaque When plaque rupture there would be exposure of tunica intima —->blood clot - In childhood we have fatty streak CHOLESTEROLOSIS - Atheroma (oma- tumor) - containing lipid Yellow, flat deposits on the mucosal surface of - Causes myocardial (heart attack) the gallbladder Normal vs cholesterolosis 11  B. AGGREGATION OF ABNORMAL PROTEINS Abnormal or misfolded proteins may deposit in tissues and interfere with normal functions Gallbladder - simple columnar epit. C. ACCUMULATION OF CYTOSKELETAL NIEMANN-PICK DISEASE PROTEINS Lysosomal storage disease Alcoholic Hyaline (Mallory body) Defective cholesterol esterification Composed of keratin intermediate filament Eosinophilic (bright pink or bright red) cytoplasmic inclusion in liver cells Basophilic (dark blue or purple) Characteristic of alcoholic liver disease - Foamy macrophages within the hepatocytes Neurofibrillary Tangles Neurofilament accumulation seen in Alzheimer Disease Choles- nucleus is in the middle Trigly - nucleus in the periphery 1. PROTEIN REABSORPTION DROPLETS Seen in renal diseases associated with PROTEIN ACCUMULATIONS proteinuria MECHANISMS In disorders with heavy protein leakage A. DEFECTS IN PROTEIN BINDING across the glomerular filter Defective intracellular transport and Increased reabsorption of protein into the secretion of proteins vesicles Example: Alpha 1-antitrypsin deficiency ○ Slow protein folding ○ Protein aggregates in the endoplasmic reticulum of the liver and thus not secreted 2. RUSSELL BODIES seen in plasma cells 12  Immunoglobulin inclusions contained within vesicles of dilated rough endoplasmic reticulum Endoplasmic reticulum becomes hugely distended, producing large, homogenous, eosinophilic inclusion PAS - bright red or pink - Kapag lipid, cholesterol, protein hindi mag stain - Only glycogen and carbohydrate derivatives will get stained PIGMENT ACCUMULATION 1. CARBON (COAL DUST) Most common exogenous pigment Coal miners are exposed Large cells with singular nucleus - plasma cell Carbon is picked up by alveolar macrophages and transported thru the GLYCOGEN ACCUMULATIONS lymphatic channels to the regional lymph - storage form of glucose nodes 1. DIABETES MELLITUS Carbon particles are deposited in the Increase glucose in the blood parenchyma of the lungs Abnormal glucose/glycogen metabolism Vacuoles in cytoplasm COAL WORKERS PNEUMOCONIOSIS Glycogen is found in: (ANTHRACOSIS) ○ Renal tubular epithelial cells Serious lung disease seen in coal miners ○ Liver cells Carbon aggregates induce fibroblastic ○ Islets of Langerhans reactions and emphysema ○ Heart muscles Cross section of the lung 2. GLYCOGEN STORAGE DISEASES Abnormal glucose/glycogen metabolism Vacuoles in cytoplasm 2. TATTOOING A form of localized exogenous pigmentation of skin Deposited in the dermis 13  The pigments inoculated are phagocytosed by dermal macrophages 5. BILIRUBIN The pigments do not evoke any Derived from hemoglobin inflammatory response (relatively benign) Deposition of bilirubin occurs due to elevated production, decreased uptake, or blockage within the hepatobiliary tree Manifestation: Jaundice Yellowish discoloration of the skin Icteresia Yellowish discoloration of the bulbar 3. LIPOFUSCIN conjunctiva, occurs due to cholestasis Aging pigment, wear-and-tear pigment Cholestasis Derived from lipid peroxidation of Stagnation in bile secretion and flow polyunsaturated lipids of subcellular membranes Increased production of bilirubin — developed Seen in cells undergoing slow regressive bilirubin accumulation changes ○ Commonly in the liver and heart of aging patients ○ Patients with severe malnutrition 6. HEMOSIDERIN Derived from hemoglobin Golden yellow to brown Storage form of iron thus it contains ferritin Ferritin forms hemosiderin granules when there is: ○ Local excess of iron (seen in hemorrhages in tissues) ○ Systemic excess of iron (occurs in 4. MELANIN hemolytic anemia, multiple Brown-black pigment transfusions) Molecule responsible for many biological functions including pigmentation of skin and hair; photoprotection of skin and eye Melanocytes - production of melanin (stratum basale) Deposited in the stratum basale of the epidermis 14  2. METASTATIC CALCIFICATION Different region Calcium deposition in normal tissues PATHOLOGIC CALCIFICATIONS Almost always results from hypercalcemia - deposition of calcium within the tissue secondary to disturbance in calcium 1. DYSTROPHIC CALCIFICATION metabolism Calcium deposition occurs locally in dying Can occur widely throughout the body but tissues principally affects the interstitial tissues of Occurs despite normal calcium serum the levels and absence of derangements in ○ Kidneys calcium metabolism ○ Lungs ○ Gastric mucosa ○ Vasculature Placenta: CELLULAR INJURY ETIOLOGY OXYGEN DEPRIVATION (HYPOXIA) Causes cell injury by reducing aerobic oxidative respiration Caused by: ○ Reduced blood flow (ischemia) ○ Inadequate oxygenation of the blood due to cardiorespiratory failure Aorta leaflets: ○ Decreased oxygen-carrying PSAMMOMA BODIES capacity of the blood, as in anemia Round microscopic calcific collections or carbon monoxide poisoning Found in a diverse group of tumors: ○ Papillary thyroid carcinoma PHYSICAL AGENTS ○ Serous cystadenoma of ovary Mechanical trauma ○ Meningioma Extremes of temperature (burns and deep cold) 15  Sudden changes in atmospheric pressure INFLUX OF CALCIUM Radiation Intracellular calcium Electric shock ○ Very low concentrations (