UNIT 1 Basic concepts of pathophysiology

BASIC CONCEPTS OF PATHOPHYSIOLOGY UNIT 1 1.1 Cellular biology : 

BASIC CONCEPTS OF PATHOPHYSIOLOGY UNIT 1 1.1 Cellular biology 11/4/2011 Mavole johnson Nzau, PhD

Outline: 

Outline Cell Structure and Organelles Cell Molecular Components Water and Chemical properties Cell Membrane Osmotic Properties of cells Cell molecule transportation 11/4/2011 Mavole johnson Nzau, PhD

Structure of Animal Cells: 

Structure of Animal Cells Cell Video 11/4/2011 Mavole johnson Nzau, PhD

Cell Organelles: 

Cell Organelles Nucleus 1 Nuclear envelope Chromatin and DNA Nucleolus Mitochondria Double membrane Mitochondrial (maternal) DNA “Power House” of the cell Food converted into energy Adenosine triphosphate (ATP) Consumes Oxygen, produces CO 2 11/4/2011 Mavole johnson Nzau, PhD

What is ATP?: 

What is ATP? Nucleotides “Carry” chemical energy from easily hydrolyzed phosphoanhydride bonds Combine to form coenzymes (coenzyme A (CoA) Used as signaling molecules (cyclic AMP) 11/4/2011 Mavole johnson Nzau, PhD

Cell Organelles: 

Cell Organelles Endoplasmic Reticulum Site where cell membrane and exported material is made Ribosomes (rough) Make protiens Smooth ER- lipids Golgi Apparatus Recieves and modifies Directs new materials Lysosomes Intracellular digestion Releases nutrients Breakdown of waste 11/4/2011 Mavole johnson Nzau, PhD

Cell Organelles: 

Cell Organelles Peroxisomes Hydrogen Peroxide generated and degraded Cytosol Water based gel Chemical reactions Cytoskeleton Filaments (actin, intermediate and microtubules) Movement of organelles and cell Structure/strengthen cell Vessicles Material transport Membrane, ER, Golgi derived vessicles 11/4/2011 Mavole johnson Nzau, PhD

Organic molecules of Cells : 

Organic molecules of Cells Proteins Carbohydrates Lipids Nucleic acids 11/4/2011 Mavole johnson Nzau, PhD

Proteins: 

Proteins Most diverse and complex macromolecules in the cell Used for structure, function and information Made of linearly arranged amino acid residues “folded” up with “active” regions 11/4/2011 Mavole johnson Nzau, PhD

Types of Proteins: 

Types of Proteins 1) Enzymes – catalyzes covalent bond breakage or formation 2) Structural – collagen, elastin, keratin, etc. 3) Motility – actin, myosin, tubulin, etc. 4) Regulatory – bind to DNA to switch genes on or off 5) Storage – ovalbumin, casein, etc. 6) Hormonal – insulin, nerve growth factor (NGF), etc. 7) Receptors – hormone and neurotransmitter receptors 8) Transport – carries small molecules or irons 9) Special purpose proteins – green fluorescent protein, etc. 11/4/2011 Mavole johnson Nzau, PhD

Lipids: 

Lipids Hydrophobic molecules Energy storage, membrane components, signal molecules Triglycerides (fat), phospholipids, waxes, sterols Sugars, storage (glycogen, starch), Structural polymers (cellulose and chitin) Major substrates of energy metabolism Carbohydrates 11/4/2011 Mavole johnson Nzau, PhD

Nucleic Acids: 

Nucleic Acids DNA (deoxyribonucleic acid) and RNA encode genetic information for synthesis of all proteins Building blocks of life 11/4/2011 Mavole johnson Nzau, PhD

Slide 13: 

11/4/2011 Mavole johnson Nzau, PhD

Water Molecule: 

Water Molecule Polarity of H 2 0 allows H bonding Water disassociates into H + and OH - Imbalance of H+ and OH- give rise to “acids and bases” - Measured by the pH pH influence charges of amino acid groups on protein, causing a specific activity Buffering systems maintain intracelluar and extracellular pH (Figure 3-6, pg 46) 11/4/2011 Mavole johnson Nzau, PhD

Water Molecule: 

Water Molecule Hydrophobic “Water-fearing” Molecule is not polar, cannot form H bonds and is “repelled” from water Insoluble Hydrophillic “Water-loving” Molecule is polar, forms H bonds with water Soluble 11/4/2011 Mavole johnson Nzau, PhD

Cell Membrane: 

Cell Membrane 11/4/2011 Mavole johnson Nzau, PhD

Cell Membrane Composition: 

Cell Membrane Composition Plasma membrane encloses cell and cell organelles Made of hydrophobic and hydrophillic components Semi-permeable and fluid-like “lipid bilayer” 11/4/2011 Mavole johnson Nzau, PhD

Cell Membrane Composition: 

Cell Membrane Composition Integral proteins interact with “lipid bilayer” Passive transport pores and channels Active transport pumps and carriers Membrane-linked enzymes, receptors and transducers Sterols stabilize the lipid bilayer Cholesterol (Figure 4-4, pg 81) 11/4/2011 Mavole johnson Nzau, PhD

Slide 19: 

(Figure 4-2, pg 80) 11/4/2011 Mavole johnson Nzau, PhD

Lipid Molecules: 

Lipid Molecules (Figure 4-3, pg 81) 11/4/2011 Mavole johnson Nzau, PhD

Osmotic Properties of Cells: 

Osmotic Properties of Cells Osmosis (Greek, osmos “to push”) Movement of water down its concentration gradient Hydrostatic pressure Movement of water causes fluid mechanical pressure Pressure gradient across a semi-permeable membrane 11/4/2011 Mavole johnson Nzau, PhD

Hydrostatic pressure: 

Hydrostatic pressure (Figure 4-9, pg 85) 11/4/2011 Mavole johnson Nzau, PhD

Donnan Equilibrium: 

Donnan Equilibrium Semi-permeable membrane Deionized water Add Ions Balanced charges among both sides (Figure 4-9, pg 81) 11/4/2011 Mavole johnson Nzau, PhD

Donnan Equilibrium: 

Add anion More Cl - leaves I to balance charges Donnan Equilibrium Diffusion 11/4/2011 Mavole johnson Nzau, PhD

Ionic Steady State: 

Ionic Steady State Potaasium cations most abundant inside the cell Chloride anions ions most abundant outside the cell Sodium cations most abundant outside the cell 11/4/2011 Mavole johnson Nzau, PhD

Donnan equilibrium: 

Donnan equilibrium [K + ] i K+ A- Na+ Ca2+ Na+ Na+ K+ K+ Cl- A- A- A- [K + ] ii [Cl - ] ii [Cl - ] i = 11/4/2011 Mavole johnson Nzau, PhD

Erythrocyte cell equilibrium: 

Erythrocyte cell equilibrium No osmotic pressure - cell is in an isotonic solution - Water does not cross membrane Increased [Osmotic] in cytoplasm - cell is in an hypotonic solution - Water enters cell, swelling Decreased [Osmotic] in cytoplasm - cell is in an hypotonic solution - Water leaves cell, shrinking (Figure 4-14, pg 90) 11/4/2011 Mavole johnson Nzau, PhD

Cell Lysis: 

Cell Lysis Using hypotonic solution Or interfering with Na+ equilibrium causes cells to burst This can be used to researchers’ advantage when isolating cells (Figure 4-16, pg 91) 11/4/2011 Mavole johnson Nzau, PhD

Molecules Related to Cell Permeability: 

Molecules Related to Cell Permeability Depends on Molecules size (electrolytes more permeable) Polarity (hydrophillic) Charge (anion vs. cation) Water vs. lipid solubility (Figures 4-18;19, pg 92) 11/4/2011 Mavole johnson Nzau, PhD

Cell Permeability: 

Cell Permeability Passive transport is carrier mediated Facilitated diffusion Solute molecule combines with a “carrier” or transporter Electrochemical gradients determines the direction Integral membrane proteins form channels 11/4/2011 Mavole johnson Nzau, PhD

Crossing the membrane: 

Crossing the membrane Simple or passive diffusion Passive transport Channels or pores Facilitated transport Assisted by membrane-floating proteins Active transport pumps & carriers ATP is required Enzymes and reactions may be required 11/4/2011 Mavole johnson Nzau, PhD

Modes of Transport: 

Modes of Transport (Figure 4-17, pg 91) 11/4/2011 Mavole johnson Nzau, PhD

Carrier-Mediated Transport: 

Carrier-Mediated Transport Integral protein binds to the solute and undergo a conformational change to transport the solute across the membrane (Figure 4-21, pg 93) 11/4/2011 Mavole johnson Nzau, PhD

Channel Mediated Transport: 

Channel Mediated Transport Proteins form aqueous pores allowing specific solutes to pass across the membrane Allow much faster transport than carrier proteins 11/4/2011 Mavole johnson Nzau, PhD

Coupled Transport: 

Coupled Transport Some solutes “go along for the ride” with a carrier protien or an ionophore Can also be a Channel coupled transport (Figure 4-22, pg 95) 11/4/2011 Mavole johnson Nzau, PhD

Active transport: 

Active transport Three main mechanisms: coupled carriers: a solute is driven uphill compensated by a different solute being transported downhill (secondary) ATP-driven pump: uphill transport is powered by ATP hydrolysis (primary) Light-driven pump: uphill transport is powered by energy from photons (bacteriorhodopsin) 11/4/2011 Mavole johnson Nzau, PhD

Active transport: 

Active transport Energy is required 11/4/2011 Mavole johnson Nzau, PhD

Na+/K+ Pump: 

Against their electrochemical gradients For every 3 ATP, 3 Na+ out, 2 K+ in Na + /K + Pump Actively transport Na+ out of the cell and K+ into the cell (Figure 4-24, pg 96) 11/4/2011 Mavole johnson Nzau, PhD

Na+/K+ Pump: 

Na+/K+ Pump Na+ exchange (symport) is also used in epithelial cells in the gut to drive the absorption of glucose from the lumen, and eventually into the bloodstream (by passive transport) (Figure 4-35, pg 105) 11/4/2011 Mavole johnson Nzau, PhD

Slide 40: 

(Figure 4-26, pg 97) 11/4/2011 Mavole johnson Nzau, PhD

Na+/K+ Pump: 

About 1/3 of ATP in an animal cell is used to power sodium-potassium pumps Na+/K+ Pump In electrically active nerve cells, which use Na+ and K+ gradients to propagate electrical signals, up to 2/3 of the ATP is used to power these pumps 11/4/2011 Mavole johnson Nzau, PhD

Endo and Exocytosis: 

Endo and Exocytosis Exocytosis - membrane vesicle fuses with cell membrane, releases enclosed material to extracellular space. Endocytosis - cell membrane invaginates, pinches in, creates vesicle enclosing contents 11/4/2011 Mavole johnson Nzau, PhD

Receptor Mediated Endocytosis: 

Receptor Mediated Endocytosis (Figure 4-30, pg 102) 11/4/2011 Mavole johnson Nzau, PhD

Genetics and genetic disorders: 

Genetics and genetic disorders The study of genes and the inheritance of traits 11/4/2011 Mavole johnson Nzau, PhD

Characteristics: 

Characteristics These are features you exhibit physically ( your looks) Example : Eye color - green 11/4/2011 Mavole johnson Nzau, PhD

Traits: 

Traits The different versions of a characteristic Example: blue, green, and brown eyes 11/4/2011 Mavole johnson Nzau, PhD

Inheritance: 

Inheritance Occurs when traits are passed down from parent to child. 11/4/2011 Mavole johnson Nzau, PhD

Genes: 

Genes Bits of information passed down from parent to child. Made of chemicals called DNA. 11/4/2011 Mavole johnson Nzau, PhD

Genetic Diseases: 

Genetic Diseases Can be passed on through genes from a parent to the child. Example : Marfan Syndrome (Individual is tall, has long arms and legs) Remember - JOE 11/4/2011 Mavole johnson Nzau, PhD

Reproduction: 

Reproduction Sexual – Sperm fertilizes an egg to produce offspring Asexual – occurs when 1 organism copies itself to produce offspring 11/4/2011 Mavole johnson Nzau, PhD

Fertilization: 

Fertilization Occurs when a sperm unites with an egg 11/4/2011 Mavole johnson Nzau, PhD

Offspring : 

Offspring Another name for the children of a male and female parent 11/4/2011 Mavole johnson Nzau, PhD

Mutation: 

Mutation Occurs when genes make a mistake mixing and produce new or different traits in the offspring. 11/4/2011 Mavole johnson Nzau, PhD

Genotype: 

Genotype A combination of alleles Example: TT, Tt, or tt *We flipped coins to determine the genotype of our critters and puppies. 11/4/2011 Mavole johnson Nzau, PhD

Alleles: 

Alleles T – is considered a dominant allele t – is considered a recessive allele TT – is dominant Tt or tT – is dominant tt - is recessive 11/4/2011 Mavole johnson Nzau, PhD

Punnett Square: 

Punnett Square Uses mom and dad’s genotypes to determine the possible traits of their offspring. 4 offspring 11/4/2011 Mavole johnson Nzau, PhD

Phenotype: 

Phenotype They are the traits determined by reading the genotype. Example : FF = black fur Black fur is the phenotype or trait 11/4/2011 Mavole johnson Nzau, PhD

Genetic Disorders: 

Genetic Disorders Inheritance of Genetic Traits 11/4/2011 Mavole johnson Nzau, PhD

Brief History: 

Brief History First there was Gregor Mendel, a monk who studied inherited characteristics. This was followed by Francis crick and James Watson who unraveled the DNA molecule. This has led us to understanding the human genome sequence 11/4/2011 Mavole johnson Nzau, PhD

Gregor Mendel: 

Gregor Mendel 1866 Gregor Mendel published the results of his investigations of the inheritance of "factors" in pea plants. 11/4/2011 Mavole johnson Nzau, PhD

Watson and Crick: 

Watson and Crick Watson and Crick made a model of the DNA molecule and proved that genes determine heredity 11/4/2011 Mavole johnson Nzau, PhD

Arthur Kornberg: 

Arthur Kornberg 1957 Arthur Kornberg (1918- ) of the U.S. produced DNA in a test tube. 11/4/2011 Mavole johnson Nzau, PhD

Genetic code: 

Genetic code 1966 The Genetic code was discovered; scientists are now able to predict characteristics by studying DNA. This leads to genetic engineering, genetic counseling. 11/4/2011 Mavole johnson Nzau, PhD

Genetic Disorders : 

Genetic Disorders 11/4/2011 Mavole johnson Nzau, PhD

Mutations: 

Mutations Gene mutations can be either inherited from a parent or acquired. A hereditary mutation is a mistake that is present in the DNA of virtually all body cells. Hereditary mutations are also called germ line mutations because the gene change exists in the reproductive cells and can be passed from generation to generation, from parent to newborn. Moreover, the mutation is copied every time body cells divide 11/4/2011 Mavole johnson Nzau, PhD

Slide 66: 

Mutations occur all the time in every cell in the body. Each cell, however, has the remarkable ability to recognize mistakes and fix them before it passes them along to its descendants. But a cell's DNA repair mechanisms can fail, or be overwhelmed, or become less efficient with age. Over time, mistakes can accumulate. 11/4/2011 Mavole johnson Nzau, PhD

Down’s Syndrome: 

Down’s Syndrome Caused by non-disjunction of the 21 st chromosome. This means that the individual has a trisomy (3 – 2lst chromosomes). 11/4/2011 Mavole johnson Nzau, PhD

Down’s Syndrome or Trisomy 21: 

Down’s Syndrome or Trisomy 21 11/4/2011 Mavole johnson Nzau, PhD

Symptoms of Down Syndrome: 

Symptoms of Down Syndrome Upward slant to eyes. Small ears that fold over at the top. Small, flattened nose. Small mouth, making tongue appear large. Short neck. Small hands with short fingers. 11/4/2011 Mavole johnson Nzau, PhD

Symptoms of Down Syndrome: 

Symptoms of Down Syndrome Low muscle tone. Single deep crease across center of palm. Looseness of joints. Small skin folds at the inner corners of the eyes. Excessive space between first and second toe. In addition, down syndrome always involves some degree of mental retardation, from mild to severe. In most cases, the mental retardation is mild to moderate. 11/4/2011 Mavole johnson Nzau, PhD

Kleinfelter’s syndrome (or Klinefleter’s): 

Kleinfelter’s syndrome (or Klinefleter’s) Disorder occurring due to nondisjunction of the X chromosome. The Sperm containing both X and Y combines with an egg containing the X, results in a male child. The egg may contribute the extra X chromosome. 11/4/2011 Mavole johnson Nzau, PhD

XXY: 

XXY Males with some development of breast tissue normally seen in females. Little body hair is present, and such person are typically tall, have small testes. Infertility results from absent sperm. Evidence of mental retardation may or may not be present. 11/4/2011 Mavole johnson Nzau, PhD

Slide 73: 

11/4/2011 Mavole johnson Nzau, PhD

Slide 74: 

Klinefleter’s 11/4/2011 Mavole johnson Nzau, PhD

Turner’s: 

Turner’s Turner syndrome is associated with underdeveloped ovaries, short stature, webbed, and is only in women. Bull neck, and broad chest. Individuals are sterile, and lack expected secondary sexual characteristics. Mental retardation typically not evident. Chromosomal or monogenic? 11/4/2011 Mavole johnson Nzau, PhD

Turner’s Syndrome: 

Turner’s Syndrome 11/4/2011 Mavole johnson Nzau, PhD

Sickle Cell Anemia: 

Sickle Cell Anemia An inherited, chronic disease in which the red blood cells, normally disc-shaped, become crescent shaped. As a result, they function abnormally and cause small blood clots. These clots give rise to recurrent painful episodes called "sickle cell pain crises". 11/4/2011 Mavole johnson Nzau, PhD

Sickle Cell : 

Sickle Cell Sickle cell disease is most commonly found in African American populations.  This disease was discovered over 80 years ago, but has not been given the attention it deserves. 11/4/2011 Mavole johnson Nzau, PhD

Cystic Fibrosis (CF): 

Cystic Fibrosis (CF) Monogenic Cause: deletion of only 3 bases on chromosome 7 Fluid in lungs, potential respiratory failure Common among Caucasians…1 in 20 are carriers Therefore is it dominant or recessive? 11/4/2011 Mavole johnson Nzau, PhD

Muscular Dystrophy: 

Muscular Dystrophy What Is Muscular Dystrophy? Muscular dystrophy is a disease in which the muscles of the body get weaker and weaker and slowly stop working because of a lack of a certain protein (see the relationship to genetics?) Can be passed on by one or both parents, depending on the form of MD (therefore is autosomal dominant and recessive) 11/4/2011 Mavole johnson Nzau, PhD

Hemophilia, the royal disease: 

Hemophilia, the royal disease Hemophilia is the oldest known hereditary bleeding disorder. Caused by a recessive gene on the X chromosome. There are about 20,000 hemophilia patients in the United States. One can bleed to death with small cuts. The severity of hemophilia is related to the amount of the clotting factor in the blood. About 70% of hemophilia patients have less than one percent of the normal amount and, thus, have severe hemophilia. 11/4/2011 Mavole johnson Nzau, PhD

Huntington’s Disease: 

Huntington’s Disease Huntington's disease (HD) is an inherited, degenerative brain disorder which results in an eventual loss of both mental and physical control. The disease is also known as Huntington's chorea. Chorea means "dance-like movements" and refers to the uncontrolled motions often associated with the disease. 11/4/2011 Mavole johnson Nzau, PhD

Slide 83: 

11/4/2011 Mavole johnson Nzau, PhD

Slide 84: 

11/4/2011 Mavole johnson Nzau, PhD

Huntington’s: 

Huntington’s Looking back at the pedigree chart is Huntington’s dominant or recessive? Scientists have discovered that the abnormal protein produced by the Huntington's disease gene, which contains an elongated stretch of amino acids called glutamines, binds more tightly to HAP-1 than the normal protein does. 11/4/2011 Mavole johnson Nzau, PhD

Diabetes : 

Diabetes Disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches, and other food into energy needed for daily life. Genetic mutation can lead to Type 1 diabetes, but no one sure if relative to a specific gene 11/4/2011 Mavole johnson Nzau, PhD

Diabetes: 

Diabetes Type 1 reveals itself in childhood, Type 2 can be made worse from excessive lifestyle Warning signs Extreme thirst Blurry vision from time to time Frequent urination Unusual fatigue or drowsiness Unexplained weight loss Diabetes is the leading cause of kidney failure, blindness, and amputation in adults, and can also lead to heart disease. 11/4/2011 Mavole johnson Nzau, PhD

Color Blindness: 

Color Blindness Cause: x-linked recessive 1/10 males have, 1/100 females have. Why the difference? Individuals are unable to distinguish shades of red-green. Are you color blind? 11/4/2011 Mavole johnson Nzau, PhD

Slide 89: 

11/4/2011 Mavole johnson Nzau, PhD

Albinism: 

Albinism Patients are unable to produce skin or eye pigments, and thus are light-sensitive Autosomal recessive Therefore, is it monogenic or chromosomal? 11/4/2011 Mavole johnson Nzau, PhD

Achondroplasia (a.k.a. dwarfism): 

Achondroplasia (a.k.a. dwarfism) Monogenic, autosomal Carriers express genes, therefore, is it dominant or recessive? There is also a disease called gigantism (Andre the Giant) 11/4/2011 Mavole johnson Nzau, PhD

Altered Cellular and Tissue Biology: 

Altered Cellular and Tissue Biology 92

Cellular Adaptation: 

93 Cellular Adaptation Physiologic vs. pathogenic Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia

Cellular Adaptation: 

94 Cellular Adaptation

Cellular Adaptation: 

95 Cellular Adaptation

Cellular Injury: 

96 Cellular Injury Reversible Irreversible

Cellular Injury Mechanisms: 

97 Cellular Injury Mechanisms Hypoxic injury Ischemia – cut off of blood flow circulation Anoxia – insufficient oxygen can be due to lowered Hb, respiration effects, respiratory poisons Cellular responses Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange Cellular swelling Reperfusion injury

Cellular Injury Mechanisms: 

98 Cellular Injury Mechanisms Free radicals and reactive oxygen species Electrically uncharged atom or group of atoms having an unpaired electron Lipid peroxidation Alteration of proteins Alteration of DNA Mechanisms for the inactivation of free radicals

Cellular Injury Mechanisms: 

99 Cellular Injury Mechanisms Chemical injury Lead – CNS toxin – interferes with neurotransmitters causing hyperactivity. Lead paints and children – anemia & lead toxicity Carbon monoxide – binds irreversibly to Hb Ethanol – cellular toxin kills cells – liver toxin- interrupts protein transport – pickles cells can cause fetal alcohol syndrome Mercury – neurotoxin can cause bone deformities Social or street drugs

Unintentional and Intentional Injuries: 

100 Unintentional and Intentional Injuries Blunt force injuries Application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues Contusion vs. hematoma – bleeding in skin & underlying layers Abrasion – removal of superficial skin layers Laceration rip, year or puncture of skin & layers Fractures – broken bones

Contusions and Hematomas: 

101 Contusions and Hematomas

Unintentional and Intentional Injuries: 

102 Unintentional and Intentional Injuries Sharp force injuries Incised wounds Stab wounds Puncture wounds Chopping wounds

Unintentional and Intentional Injuries: 

103 Unintentional and Intentional Injuries

Unintentional and Intentional Injuries: 

104 Unintentional and Intentional Injuries Gunshot wounds Entrance wounds Contact range entrance wound Intermediate range entrance wound Tattooing and stippling Indeterminate range entrance wound Exit wounds Shored exit wound

Unintentional and Intentional Injuries: 

105 Unintentional and Intentional Injuries Asphyxial injuries Caused by a failure of cells to receive or use oxygen Suffocation Strangulation Hanging, ligature, and manual strangulation Chemical asphyxiants- carbon monoxide, cyanide Drowning

Infectious Injury: 

106 Infectious Injury Pathogenicity of a microorganism – gram neg or positive will determine which antibiotics will work best – anti viral agents for viral infections Virulence of a microorganism – some strains are more dangerous than others Disease-producing potential Invasion and destruction Toxin production Production of hypersensitivity reactions

Immunologic and Inflammatory Injury: 

107 Immunologic and Inflammatory Injury Phagocytic cells – immune cells that engulf and destroy invading microbes and toxins Immune and inflammatory substances Histamine (chemical released by injured or infected cells that cause local vasodilation), antibodies (endogenous proteins that combat and identify invading cells and toxins), lymphokines (chemical produced by imune cells), complement, and enzymes Membrane alterations – leakage of cell contents due to the presence of antibodies and histamines

Injurious Genetic Factors: 

108 Injurious Genetic Factors Nuclear alterations – mutations and damage to DNA Alterations in the plasma membrane structure, shape, receptors, or transport mechanisms Examples of genetic diseases Sickle cell anemia (substitution of one amino acid in Hb structure) and muscular dystrophy (muscle tissue does not function properly

Injurious Nutritional Imbalances: 

109 Injurious Nutritional Imbalances Essential nutrients are required for cells to function normally inadequate proteins, carbohydrates, fats, vitamins, minerals Deficient intake – starvation and improper diets – protein deficiency “kwashiokor” most common, Vitamin B 12 deficiency leads to pernicious anemia Excessive intake - obesity

Temperature Extremes: 

110 Temperature Extremes Hypothermic injury Slows cellular metabolic processes Ice crystal formation and frostbite Hyperthermic injury Heat cramps Heat exhaustion Heatstroke Protein denaturation

Atmospheric Pressure Changes: 

111 Atmospheric Pressure Changes Sudden increases or decreases in atmospheric pressure Blast injury Nitrogen Narcosis or rapture of the deep Nitrogen gas has a narcotic effect (laughing gas) Decompression sickness or caisson disease “The bends”

Ionizing Radiation: 

112 Ionizing Radiation Any form of radiation capable of removing orbital electrons from atoms X-rays, gamma rays, alpha and beta particles Amount of exposure measured in RADS. People who work with X-rays must wear badge that measures dosees of exposure over time Mechanism of damage – ionization of chemicals and breakage of chemical bonds Effects of ionizing radiation

Ionizing Radiation: 

113 Ionizing Radiation

Cellular Injury : 

114 Cellular Injury Illumination injury Eyestrain, obscured vision, and cataract formation Caused by light modulation Mechanical stresses Physical impact or irritation Noise – sound can cause tisse and organ trauma Acoustic trauma and noise-induced hearing loss – tinnitus very common among performing rock band members

Manifestations of Cellular Injury: 

115 Manifestations of Cellular Injury Cellular accumulations (infiltrations) Water Lipids and carbohydrates Glycogen Proteins

Hydropic Degeneration: 

116 Hydropic Degeneration

Manifestations of Cellular Injury: 

117 Manifestations of Cellular Injury Cellular accumulations (infiltrations) Pigments Melanin, hemoproteins, bilirubin (aging brown spots) Calcium – can cause hardening of cells and altered membrane permeability Urate example is gout where urate crystals form in joints and is very painful

Cellular Death: 

118 Cellular Death Necrosis – local cell death by autodigestion Sum of cellular changes after local cell death and the process of cellular autodigestion Processes Karyolysis Nuclear dissolution and chromatin lysis Pyknosis Shrinking & Clumping of the nucleus Karyorrhexis Fragmentation of the nucleus

Cellular Death: 

119 Cellular Death

Necrosis: 

120 Necrosis Coagulative necrosis Primarily found in Kidneys, heart, and adrenal glands Protein denaturation and increased intracellular level of Ca

Coagulative Necrosis: 

121 Coagulative Necrosis

Necrosis: 

122 Necrosis Liquefactive necrosis – common after ischemic events in CNS (stroke) Neurons and glial cells of the brain die and are rich in digestive enzymes Hydrolytic enzymes causes brain tissues to become soft and liquefy – sometimes walled off and form cysts These types of cysts also form after bacterial infection due to actions of phagocytic neutrophils and fluid in cyst is called pus.

Necrosis: 

123 Necrosis Caseous necrosis Found in Tuberculous pulmonary infection Combination of coagulative and liquefactive necrosis Necrotic debris not completely digested thus tissues appear granular like clumped cheese

Necrosis: 

124 Necrosis Fat necrosis Common in Breast, pancreas, and other abdominal organs – breakdown of fats create soaps and referred to as saponification and tissue is opaque or white chalky Action of lipases – break down fats to FA and glycerols

Necrosis: 

125 Necrosis Gangrenous necrosis Clinical term Dry vs. wet gangrene Gas gangrene

Gangrenous Necrosis: 

126 Gangrenous Necrosis

Apoptosis a type of cell death different from Necrosis in that it is active self destruction of normal and pathologic tissue: 

127 Apoptosis a type of cell death different from Necrosis in that it is active self destruction of normal and pathologic tissue Programmed cellular death- found mostly to occur during development of embryo Mechanisms- specific signaling chemicals send message to cells programmed to die Necrosis vs. apoptosis- while necrosis usually effects all cells in an area apoptosis effects scattered cells killing the cells shrink quickly and disappear neatly while necrotic cells swell and lyse

Aging and Altered Cellular and Tissue Biology: 

128 Aging and Altered Cellular and Tissue Biology Aging vs. disease tissues all have accumulaion of toxic chemicals and mutation damage over time. Disease can damage and destroys cells quickly due to some pathogenic cause Normal life span - brain cells live as long as you do and the neurons in CNS once formed by age 6 do not divide. RBC live only 120 days Gender differences - women live longer than men 78 vs 81 years may be due to genetic superiority

Theories of Aging: 

129 Theories of Aging Accumulation of injurious events – the more exposure to dangerous chemicals and pathogens the faster you age Genetically controlled program – some of us are destined to live longer due to the genetic program in our cells Theories Genetic and environmental lifestyle factors Alterations of cellular control mechanisms decreased protein synthesis as you age Degenerative extracellular changes – nutrients and free radicals important

Theories of Aging: 

130 Theories of Aging

Aging: 

131 Aging Cellular aging all cells can replicate 40 – 60 times max and may be why clones do not live as long as parents Tissue and systemic aging immune function goes down with age and free radicals damage cells speeding aging Frailty – wastin syndrome of aging due to decreased protein synthesis and reduced muscle mass and lowered bone density

Fluids and electrolytes: 

Fluids and electrolytes 132

Distribution of Body Fluids: 

133 Distribution of Body Fluids Total body water (TBW) 60% of total body weight Intracellular fluid – inside the cells Extracellular fluid – not encased in cells Interstitial fluid – found in between cells and tissues Intravascular fluid- plasma found in circulatory system Lymph, synovial, intestinal, biliary, hepatic, pancreatic, CSF, sweat, urine, pleural, peritoneal, pericardial, and intraocular fluids are extracellular

Water Movement Between the ICF and ECF: 

134 Water Movement Between the ICF and ECF Osmolality – the concentrations of solutes in water Osmotic forces – solutes will influence the movement of water across membranes Aquaporins- water channel proteins in membranes Starling hypothesis Net filtration = forces favoring filtration – forces opposing filtration As fluid flows through capillary it looses water and create greater osmotic return of water as it flows toward veinule end of capillary

Water Movement Between the ICF and ECF: 

135 Water Movement Between the ICF and ECF

Net Filtration: 

136 Net Filtration Forces favoring filtration Capillary hydrostatic pressure (blood pressure) Interstitial oncotic pressure (water-pulling) Forces favoring reabsorption Plasma oncotic pressure (water-pulling) Interstitial hydrostatic pressure

Edema: 

137 Edema Accumulation of fluid within the interstitial spaces Causes: Increase in hydrostatic pressure Losses or diminished production of plasma albumin Increases in capillary permeability Lymph obstruction – elephantitus, flibitus

Edema: 

138 Edema

Water Balance: 

139 Water Balance Thirst perception Osmolality receptors in medula respond to osmotic pressue of ECF Hyperosmolality and plasma volume depletion ADH secretion from posterior pituitary – conserves water in kidney to maintain water balance

Sodium and Chloride Balance: 

140 Sodium and Chloride Balance Sodium Primary ECF cation Regulates osmotic forces Roles Neuromuscular irritability, acid-base balance, and cellular reactions Chloride Primary ECF anion Provides electroneutrality

Sodium and Chloride Balance: 

141 Sodium and Chloride Balance Renin-angiotensin system – substanced produced in both liver and kidney Angiotensin produced by liver and coverted by enzymes activated by renin from Kidney Juxta Glomerular Aparatus to a powerful vasoconstrictor. Aldosterone – hormone from adrenal gland to regulate Na and K Natriuretic peptides Atrial natriuretic peptide - hormone from heart Brain natriuretic peptide – hormone from brain Urodilantin (kidney) – Kidney hormone

Alterations in Na+, Cl–, and Water Balance: 

142 Alterations in Na + , Cl – , and Water Balance Isotonic alterations Total body water change with proportional electrolyte and water change Isotonic volume depletion Isotonic volume excess

Hypertonic Alterations: 

143 Hypertonic Alterations Hypernatremia Serum sodium >147 mEq/L Related to sodium gain or water loss Water movement from the ICF to the ECF Intracellular dehydration Manifestations Intracellular dehydration, convulsions, pulmonary edema, hypotension, tachycardia, etc.

Water Deficit: 

144 Water Deficit Dehydration Pure water deficits Renal free water clearance Manifestations Tachycardia, weak pulses, and postural hypotension Elevated hematocrit and serum sodium level

Hypochloremia: 

145 Hypochloremia Occurs with hypernatremia or a bicarbonate deficit Usually secondary to pathophysiologic processes Managed by treating underlying disorders

Hypotonic Alterations: 

146 Hypotonic Alterations Decreased osmolality Hyponatremia or free water excess Hyponatremia decreases the ECF osmotic pressure, and water moves into the cell Water movement causes symptoms related to hypovolemia

Hyponatremia: 

147 Hyponatremia Serum sodium level <135 mEq/L Sodium deficits cause plasma hypoosmolality and cellular swelling Pure sodium deficits Low intake Dilutional hyponatremia Hypoosmolar hyponatremia Hypertonic hyponatremia

Water Excess: 

148 Water Excess Compulsive water drinking Decreased urine formation Syndrome of inappropriate ADH (SIADH) ADH secretion in the absence of hypovolemia or hyperosmolality Hyponatremia with hypervolemia Manifestations: cerebral edema, muscle twitching, headache, and weight gain

Hypochloremia: 

149 Hypochloremia Usually the result of hyponatremia or elevated bicarbonate concentration Develops due to vomiting and the loss of HCl Occurs in cystic fibrosis

Potassium: 

150 Potassium Major intracellular cation Concentration maintained by the Na + /K + pump Regulates intracellular electrical neutrality in relation to Na + and H + Essential for transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction

Potassium Levels: 

151 Potassium Levels Changes in pH affect K + balance Hydrogen ions accumulate in the ICF during states of acidosis. K + shifts out to maintain a balance of cations across the membrane. Aldosterone, insulin, and catecholamines influence serum potassium levels

Hypokalemia: 

152 Hypokalemia Potassium level <3.5 mEq/L Potassium balance is described by changes in plasma potassium levels Causes can be reduced intake of potassium, increased entry of potassium, and increased loss of potassium Manifestations Membrane hyperpolarization causes a decrease in neuromuscular excitability, skeletal muscle weakness, smooth muscle atony, and cardiac dysrhythmias

Hyperkalemia: 

153 Hyperkalemia Potassium level >5.5 mEq/L Hyperkalemia is rare due to efficient renal excretion Caused by increased intake, shift of K + from ICF, decreased renal excretion, insulin deficiency, or cell trauma

Hyperkalemia: 

154 Hyperkalemia Mild attacks Hypopolarized membrane, causing neuromuscular irritability Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea Severe attacks The cell is not able to repolarize, resulting in muscle weakness, loss or muscle tone, and flaccid paralysis

Calcium: 

155 Calcium Most calcium is located in the bone as hydroxyapatite Necessary for structure of bones and teeth, blood clotting, hormone secretion, and cell receptor function

Phosphate: 

156 Phosphate Like calcium, most phosphate (85%) is also located in the bone Necessary for high-energy bonds located in creatine phosphate and ATP and acts as an anion buffer Calcium and phosphate concentrations are rigidly controlled Ca ++ x HPO 4 – – = K + (constant) If the concentration of one increases, that of the other decreases

Calcium and Phosphate: 

157 Calcium and Phosphate Regulated by three hormones Parathyroid hormone (PTH) Increases plasma calcium levels Vitamin D Fat-soluble steroid; increases calcium absorption from the GI tract Calcitonin Decreases plasma calcium levels

Hypocalcemia and Hypercalcemia: 

158 Hypocalcemia and Hypercalcemia Hypocalcemia Decreases the block of Na + into the cell Increased neuromuscular excitability (partial depolarization) Muscle cramps Hypercalcemia Increases the block of Na + into the cell Decreased neuromuscular excitability Muscle weakness Increased bone fractures Kidney stones Constipation

Hypophosphatemia and Hyperphosphatemia: 

159 Hypophosphatemia and Hyperphosphatemia Hypophosphatemia Osteomalacia (soft bones) Muscle weakness Bleeding disorders (platelet impairment) Anemia Leukocyte alterations Antacids bind phosphate Hyperphosphatemia See Hypocalcemia High phosphate levels are related to the low calcium levels

Magnesium: 

160 Magnesium Intracellular cation Plasma concentration is 1.8 to 2.4 mEq/L Acts as a cofactor in protein and nucleic acid synthesis reactions Required for ATPase activity Decreases acetylcholine release at the neuromuscular junction

Hypomagnesemia and Hypermagnesemia: 

161 Hypomagnesemia and Hypermagnesemia Hypomagnesemia Associated with hypocalcemia and hypokalemia Neuromuscular irritability Tetany Convulsions Hyperactive reflexes Hypermagnesemia Skeletal muscle depression Muscle weakness Hypotension Respiratory depression Lethargy, drowsiness Bradycardia

pH: 

162 pH Inverse logarithm of the H + concentration If the H + are high in number, the pH is low (acidic). If the H + are low in number, the pH is high (alkaline). The pH scale ranges from 0 to 14: 0 is very acidic, 14 is very alkaline. Each number represents a factor of 10. If a solution moves from a pH of 6 to a pH of 5, the H + have increased 10 times.

pH: 

163 pH Acids are formed as end products of protein, carbohydrate, and fat metabolism To maintain the body’s normal pH (7.35-7.45) the H + must be neutralized or excreted The bones, lungs, and kidneys are the major organs involved in the regulation of acid and base balance

pH: 

164 pH Body acids exist in two forms Volatile H 2 CO 3 (can be eliminated as CO 2 gas) Nonvolatile Sulfuric, phosphoric, and other organic acids Eliminated by the renal tubules with the regulation of HCO 3 –

Buffering Systems: 

165 Buffering Systems A buffer is a chemical that can bind excessive H + or OH – without a significant change in pH A buffering pair consists of a weak acid and its conjugate base The most important plasma buffering systems are the carbonic acid–bicarbonate system and hemoglobin

Carbonic Acid–Bicarbonate Pair: 

166 Carbonic Acid–Bicarbonate Pair Operates in both the lung and the kidney The greater the partial pressure of carbon dioxide, the more carbonic acid is formed At a pH of 7.4, the ratio of bicarbonate to carbonic acid is 20:1 Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained

Carbonic Acid–Bicarbonate Pair: 

167 Carbonic Acid–Bicarbonate Pair If the amount of bicarbonate decreases, the pH decreases, causing a state of acidosis The pH can be returned to normal if the amount of carbonic acid also decreases This type of pH adjustment is referred to as compensation The respiratory system compensates by increasing or decreasing ventilation The renal system compensates by producing acidic or alkaline urine

Carbonic Acid–Bicarbonate Pair: 

168 Carbonic Acid–Bicarbonate Pair

Other Buffering Systems: 

169 Other Buffering Systems Protein buffering Proteins have negative charges, so they can serve as buffers for H + Renal buffering Secretion of H + in the urine and reabsorption of HCO 3 – Cellular ion exchange Exchange of K + for H + in acidosis and alkalosis

Acid-Base Imbalances: 

170 Acid-Base Imbalances Normal arterial blood pH 7.35 to 7.45 Obtained by arterial blood gas (ABG) sampling Acidosis Systemic increase in H + concentration Alkalosis Systemic decrease in H + concentration

Acidosis and Alkalosis: 

171 Acidosis and Alkalosis Four categories of acid-base imbalances: Respiratory acidosis— elevation of pCO 2 due to ventilation depression Respiratory alkalosis— depression of pCO 2 due to alveolar hyperventilation Metabolic acidosis— depression of HCO 3 – or an increase in non-carbonic acids Metabolic alkalosis— elevation of HCO 3 – usually due to an excessive loss of metabolic acids

Metabolic Acidosis: 

172 Metabolic Acidosis

Anion Gap: 

173 Anion Gap Used cautiously to distinguish different types of metabolic acidosis By rule, the concentration of anions (–) should equal the concentration of cations (+). Not all normal anions are routinely measured. Normal anion gap = Na + + K + = Cl – + HCO 3 – + 10 to 12 mEq/L (other misc. anions [the ones we don’t measure]—phosphates, sulfates, organic acids, etc.)

Anion Gap: 

174 Anion Gap An abnormal anion gap occurs due to an increased level of an abnormal unmeasured anion Examples: DKA—ketones, salicylate poisoning, lactic acidosis—increased lactic acid, renal failure, etc. As these abnormal anions accumulate, the measured anions have to decrease to maintain electroneutrality

Metabolic Alkalosis: 

175 Metabolic Alkalosis

Respiratory Acidosis: 

176 Respiratory Acidosis

Respiratory Alkalosis: 

177 Respiratory Alkalosis