1. Cells - Birhan .ppt

Cells Introduction Medical Biochemistry studies The chemical composition of human body The metabolic processes in our body There Clinical correlation The cellular components are made from biomolecules Biomolecules are large biological molecules...

Cells Introduction Medical Biochemistry studies The chemical composition of human body The metabolic processes in our body There Clinical correlation The cellular components are made from biomolecules Biomolecules are large biological molecules The major ones are Bioorganic Carbohydrate Lipid Amino acids and proteins Nucleic acids Vitamins Bioinorganic Water Inorganic salts Con’t Biochemistry is important in solving health problems such as: metabolic disorder, nutritional problems, diagnosis problems and drug interactions and others. Con’t Composition of the human body in terms of major types of biochemical substances:  Protein 15 %  Lipids 8%  Carbohydrates and nucleic acids 2 %  Water and inorganic salts 75 % The bioorganic molecules are complex and large molecules (called polymers) that are composed of similar repeating subunits (called monomers). Con’t Monomers of the bioorganic molecules are: Carbohydrates-monosaccharide Protein-amino acids Lipids- Fatty acids Nucleic acids-nucleotides 6 Cells A unit of biological activity Delimited by a semi-permeable membrane and Capable of self reproduction An integrated and continuously changing systems Simplest integrated organization in living systems, Capable of independent survival Great diversity among cells of a complex organism All cells show remarkable similarities in Constituents, metabolic reactions and hereditary mechanisms The metabolic pathways of glucose degradation in bacteria, man and plants are essentially the same Con’t A cell a “bag” of chemicals capable of surviving and replacing itself Chemicals inside differ in various ways from outside The barrier is a very thin living membrane All living cells are surrounded by a membrane Cellular features Size and shape of cells are related to the cell’s functions Cells vary in size and shape Most cells are microscopic in size Size varies small cells of bacteria 0.2-5.0μm Small in size Volume of the cell increases faster than surface area Small in size More surface area As cell size increases a point is reached the surface area can no longer service the needs of the volume of the cell. This point is about 100 um for a spherical cell. Female Egg – largest cell in the human body; seen without the aid of a microscope Most cells are visible only with a microscope. THE CELL'S NUCLEUS (THE BRAIN) CAN ONLY CONTROL A CERTAIN AMOUNT OF LIVING, ACTIVE CYTOPLASM  Con’t Typical cells range from 5-50 micrometers (microns) in diameter Prokaryotic and Eukaryotic cells Prokaryotic Made up of cells which lack a nucleus Prokaryotic cells – before the nucleus The nuclear material is not bounded by a definite nuclear membrane Generally much smaller than eukaryotic cells Single celled organisms Includes the bacteria and blue green algae – cyanobacteria have one or more nuclear regions containing a genetic material – DNA sometimes called nucleoids Nucleoids are not enclosed by a separate membrane Have a plasma membrane not have distinct internal membrane system in the form of organelle Con’t Eukaryotic cells The cell has Its own control center Internal transport system Power plants Factories for making needed materials Packaging plants A “self destruct” system The nucleus is the largest of all the intercellular organelles Prokaryotic Examples ONLY Bacteria Eukaryotic Example Plasma membrane maintain an appropriate internal environment perform many chemical reactions necessary to sustain life All cells are physically separated from the outside world a limiting plasma membrane Complex and dynamic structures made from molecules Permitting selective interactions between internal membrane system within the cell and between the cell and the environment Con’t All cells are bound by a thin membrane called the plasmalemma This membrane is not visible under the light microscope The structure seen under the light microscope - Cell membrane plasmalemma + surrounding cell cement In the broad sense the term cell membrane includes the limiting membranes like Nuclear envelope Endoplasmic reticulum Golgi apparatus These membranes however resemble the plasmalemma in having no cell cement Con’t The plasma membrane (surface cell membrane) may be protected by other coverings The plasma membrane of the egg is surrounded by the vitelline membrane and the jelly layer Both of which secreted by the ovary Chemical composition and structure Cell membranes Not more than 10 nm thick Essentially consist of lipoproteins Which are special non-bonded combinations of lipids with proteins Contain about 60% protein and 40% carbohydrate by dry weight Carbohydrate usually as glycoproteins and glycolipids 1-10% of the total dry weight in glycoproteins and glycolipids Con’t Lipids Cell membrane lipids are polar lipids Contain hydrophilic heads and hydrophobic tails The three main constituents of membrane lipids are Phospholipids Glycolipids Cholesterol Phospholipids consists of Polar head containing phosphate and two non-polar molecules Polar – uneven distribution of charge Phospholipid molecule the head is hydrophilic (water loving) and the tails are hydrophobic (water hating) Con’t Membrane also contain Glycolipids Lipids combine with CHO Like phospholipids they have polar heads and non polar tails Cholesterol Slightly polar at one end Proteins Membrane contain three different classes of proteins Structural proteins Enzymes Carrier proteins Con’t Structural proteins back bone of the cell membrane Extremely lipophilic The plasma membrane consist largely of structural proteins Enzymes Major component of many membranes Catalytic proteins Endoplasmic reticulum, mitochondria and plasma membrane contain many enzymes Con’t Carrier proteins or permeates Transport substances across the membrane against the concentration gradient Plasma membrane proteins fall in two Intrinsic or integral proteins Extrinsic or peripheral proteins Human erythrocyte glycoproteins consist of three distinct regions An N-terminal part – external to the membrane and containing all the carbohydrates A middle hydrophobic region – located within the membrane Intramembranous part intimately associated with the membrane phospholipids A hydrophilic C-terminal portion on the internal side of the membrane Con’t The extrinsic or peripheral proteins are Readily dissociated from the membrane Can be isolated relatively by simple means manipulation of ionic strength or PH Believed to be associated with the polar heads of the lipid molecules The polar amino acids are on the outer surface of the protein molecule and the non-polar acids in the interior Functions of cell membrane The cell membrane Active component of the living cell Not simply an envelope giving mechanical strength and shape some protection to the cell Play a complex and dynamic role in life processes Many metabolic processes occur within the components of intracellular membrane system Transport, signal transduction.. Regulates the traffic of materials between the interior and outer environment Channel and carrier molecules Selective transport of polar molecules and ions across the membrane facilitated diffusion and active transport Con’t Cell recognition and adhesion Leucocytes recognize foreign cells like bacteria and engulf by phagocytosis Leave other cell types in the blood alone Macrophages of the spleen differentiate between healthy and worn out erythrocytes destroy worn out cells by phagocytosis The cell surface carries both glycosyl transferases and glycosyl acceptor molecules- oligosaccharides made up of monosaccharides units The transferase of one cell binds with a specific receptor molecule of a neighboring cell in an enzyme substrate reaction Con’t Antigen specificity Glycoprotein on the surface determine the antigen specificities of the cells Antigens act as cell identity markers or “name tags” They are glycoproteins (proteins with branching carbohydrate side chains like “antennae”) There is an enormous number of possible shapes to these side chains So each type of cell can have its own specific markers This enables cells recognize other cells behave in an organized way Con’t Hormone receptors Cell membrane contains receptors which recognize specific hormones and convey the information to the interior of the cells This stimulates a change in the metabolism of the cell Hormone receptors most commonly located in the plasma membrane on the outer surface of the membrane Receptors for steroid hormones located in the cytoplasm These hormones penetrate the plasm membrane bind to the cytoplasm receptor Con’t Secretion polypeptide chains synthesized by ribosomes Released into the lumen of ER cisternae Next transported to the Golgi apparatus Stored in secretory vesicles Secretory vesicles released from the Golgi apparatuses Move to the periphery of the cell and fuse with the plasma membrane Fusion depends upon the interaction Cell History Hans and Zacharias Janssen 1590 Dutch lens makers Invented the 1st compound microscope Two lenses in a tube Robert Hook 1665 Used a microscope to examine cork-dead oak tree Called what he saw ‘ Cells’ Cytology – study of cells Con’t Anton Van Leeuwenhoek 1673 Dutch amateur scientist Observed some of the first living cells From pond water and escaping's of his teeth Under a simple (1 lens) microscope Named small organisms ‘animalcules’ Now believed to be actually protozoa Robert Brown 1833 Discovered the nucleus Cell Theory Matthias Schleiden 1838 A German botanist Theodore Schwann 1839 A German zoologist Viewed plants and animals under a microscope Plants and animals made of cells – all plants and all animals Rudolph Virchow 1855 Observed cells dividing under microscope All cells come from preexisting cells by cell division Debunked the ‘Theory of spontaneous generation’ Collaborated with the two to develop ‘The cell theory’ Con’t The modern cell theory - Combining Schleiden, Schwann and Virchow  All living organisms are made up of cells.  Cells are the most basic unit of life.  Cells only come from the division of pre- existing cells. The cell evolution When did life begin? Evidence in metamorphic rocks that life existed 3.85 billions years ago high C12/C13 fraction in rock layers suggests life Biological processes prefer C12 to C13 Find lower fraction of C13 Non-biological processes have no preference, so find equal amounts Evidence suggests life as long as 3.85 billion years ago and definitely at 3.5 billion years ago Life rose and dominated the planet between 100-500 million years Con’t Where did life begin? Land is unlikely No O2, no ozone: UV destroys molecular bonds Shallow ponds Once favored, full of organic material When evaporated, organic chemical concentration increases making it easier to combine complex molecules leading to life Current experiments indicate lack of chemical energy sufficient to support life Deep-sea vents/hot springs DNA evidence suggests that early organisms survived in conditions similar to deep-sea vents Plenty of chemical energy available Con’t How did life begin? Simplest organisms today and those dated 3.5 billion years ago are remarkabley advanced What are the natural chemical processes that could have led to life? Assumptions Life began under chemical conditions of early Earth Life did not migrate to Earth In 1920’s, scientists hypothesized that the chemicals in the early atmosphere, fueled by sunlight, would spontaneously create organic molecules Tested by Miller-Urey experiment 1950’s Con’t Form molecules to the first cell Earth on its 1st billion years Violent place Volcanic eruptions, lightening and torrential rains No free oxygen No ozone to absorb radiation Under such conditions Simple organic compounds formed Mixture of gases such as CO2, CH4, NH3, H2 form small organic molecules HCN, HCHO Heated with water, energized by electric discharge or UV radiation Further they form amino acids sugars, purines pyrimidines – class of small organic compounds found in cells Complex chemical systems Amino acids by peptide bond to polypeptides Nucleotides by phosphodiester bond to polynucleotides RNA and DNA Earliest polymers May have formed in any of several ways For specific roles in the cell selected based on their chemical properties Formed By heating of organic compounds By catalytic activity of other inorganic polyphosphates or crude mineral catalysts Under lab conditions polymers of variable lengths randomly formed Once formed Influence subsequent reactions by acting as a catalyst Autocatalytic system Molecules having like the characteristics of living matter The ability to catalyze reaction that lead, directly or indirectly to production of more molecules of the catalyst itself Compete with other systems on the same feedstock Decay toward chemical equilibrium and die If deprived of its feedstock At wrong temperature A chemical system of organic monomers and polymers that function together to generate more molecules of the same type fueled by simple raw material supplement in the environment Production of catalysts with special self promoting favored Molecules most efficient in aiding their own production divert raw materials from the production of other substances Con’t Polypeptides In present day cells the most versatile catalysts But no known way in which one such molecules can reproduce itself Can not specify the formation of another same sequence Polynucleotides Limited capabilities as catalyst Can directly guide the formation of exact copies of their own sequence Depend on complementary pairing of nucleotide subunits One act as a template Con’t Originally cells with relatively simple chemistry could survive and grow As evolution proceeded Competition for limited natural resources become intense Organisms manufacture useful organic molecules become more efficient Had a strong selective advantage Cells enclosed got advantage More proteins produced 43 Early cell like structure Advantages to enclosing enzymes with RNA molecules Close proximity increases rate of reactions between them Isolate contents from outside world Grow in size until unstable then split to form a ‘daughter’ cell Selectively allow other types of molecules to pass in/out of membrane Eucaryotic cells Molecular oxygen accumulated in the atmosphere Anaerobic organisms with which life begun, what happened to them? At a severe disadvantage Some became extinct Developed a capacity for respiration Found oxygen absent niches Predators or parasites on aerobic cells Formed intimate association with an aerobic type of cells, living in symbiosis Many present day bacteria respire like mitochondria Eucaryotic cells are descendants of primitive anaerobic organisms In oxygen rich world survived by engulfing aerobic bacteria For the sake of their capacity to consume atmospheric oxygen and produce energy 46 Endosymbiotic theory Lynn Margulis In 1970, American provided evidence that some organelles within cells were at one time free living cells themselves Supporting evidence included organelles with their own DNA Chloroplast and Mitochondria copyright cmassengale 48 Cellular organelles Cells: The fundamental structural and functional units of living organisms Natural reaction vessels for biochemical reactions Biochemical reactions take place in a very small size of the cell, in mild physiological conditions of temperature, pressure and at constant PH in an aqueous medium. Eukaryotic cells Plasma membrane Every cell has this thin surrounding membrane The cell membrane provides the cell with permeability barrier The membrane takes up large molecules in by endocytosis. Intracellularely synthesized large molecules are released to the outside of the cell by exocytosis. 51 Con’t In and out transport of many molecules particularly polar molecules and ions, is by means of active transportation Small molecules and gases can diffuse through the cell membrane by passive transport Organelles Structures inside a cell with some characteristic functions. These sub-cellular structures have different biochemical activities and play different roles within the cell.  Nucleus Largest cell organelle Enclosed by an envelope of two membranes perforated by nuclear pores A complex of DNA and proteins called chromatin is distributed throughout the nucleoplasem. Contains the enzymes for DNA replication and for its transcription into RNA Chromosomes contain DNA the molecule of inheritance. DNA is organized into genes which control all the activities of the cell nuclear division is the basis of cell replication and hence reproduction. Contains a small round nucleolus produces ribosomal RNA which makes ribosomes. 54 Endoplasmic reticulum (ER) ER is a series of membrane tubules and vesicles which extend throughout much of the cytoplasm. They are of two types, smooth endoplasmic reticulum, which is not studded with ribosome and rough endoplasmic reticulum with studded ribosome. The rough endoplasmic reticulum bound ribosomes are engaged in biosynthesis of proteins to be secreted out from the cell or to be incorporated in a cell membrane. Smooth endoplasmic reticulum contains membrane bound enzymes for metabolic pathway such as fatty acid synthesis. The internal structure of endoplasmic reticulum is called cisternae. 56 Ribosomes Small non-membrane bound organelles. Contain two sub units Site of protein synthesis. Protein factory of the cell Either free floating or attached to the Endoplasmic Reticulum 57  The Golgi complex A series of flattened sacs that modifies, packages, stores, and transport materials out of the cell. Works with the ribosomes and Endoplasmic Reticulum. The Golgi complex are membrane vesicles mainly involved in post-translational modification of proteins. Proteins and other substances are transported out of the cell in vesicles, which bud off the Golgi complex. The release of the contents occurs by exocytosis in which the vesicles fuse with plasma membrane. 59  Lysosomes Lysosomes are large membrane vesicles that are formed by budding off from the Golgi complex. They contain hydrolytic enzymes for the degradation of proteins nucleic acids lipids and carbohydrates. Lysosomes are responsible for the degradation of macromolecules taken in to the cell by endocytosis and unwanted intracellular biomlecules, by the process known as autophagy, and for the complete destruction of cellular structure after cell death by the process known as autolysis. 61  Mitochondria They are the power house of eukaryotic cells in which most of ATP is produced. Contains its own DNA; mDNA The outer membrane forms smooth envelope and it is freely permeable to most substances. Relatively few enzymes are associated with it. The inner membrane shows numerous invaginations (folds) called cristae, which provides a large surface area. It is associated with many enzymes involved in generation of ATP. The space within the inner membrane is called mitochondrial matrix, and it contains the soluble enzymes for important metabolic pathways such as Krebs cycle and β-oxidation. 63 Centrioles Found only in animal cells Paired structures near nucleus Made of bundle of microtubules Appear during cell division forming mitotic spindle Help to pull chromosome pairs apart to opposite ends of the cell Vacuoles Fluid filled sacks for storage Small or absent in animal cells Plant cells have a large Central Vacuole No vacuoles in bacterial cells In plants, they store Cell Sap Includes storage of sugars, proteins, minerals, lipids, wastes, salts, water, and enzymes  Cytoplasm The cytoplasm is intracellular space other than the organelles. The soluble part of the cytoplasm is called cytosol. Jelly-like substance enclosed by cell membrane Provides a medium for chemical reactions to take place This is soluble part of the cytoplasm contains many proteins including enzymes for Eg Glycolysis, Pentose phosphate pathway, And for many other biosynthetic pathways 67 Cytoskeleton Cytoskeleton Extending throughout the cytoplasm of most cells a net work of proteins filaments. These filaments are of three types  Microtubules  Microfibrilles  Intermediate filaments These filaments are involved in  Maintaining the cell shape  Movement of cell components such as chromosomes  Endocytosis and exocytosis Water, Acid-Base and Buffer  Water Water is a polar molecule Water molecules are inter linked by hydrogen bonds Essential for life It is possible to live without food than without water. Water makes up about 45-75% of your body weight 2/3 intracellular fluid-ICF and 1/3 extracellular fluid ECF Form ECF ¾ are interstitial and ¼ is intravascular H H O H O O H H H hydrogen bond O H O H H H Important characteristics of water High dissolving power Facilitate absorption, transportation, metabolism and excretion High heat capacity Contribute to body thermal regulation at 37 oC High surface tension Used for making membrane Water naturally auto dissociates is the base to understand PH concept Ionization and PH Some of Water molecules auto-dissociate naturally The amount of water molecules dissociated is 1.0 x 10-7 M PH by definition is – log [H+] There fore the PH of pure water is PH = - log 1.0 x 10-7 = 7 is taken as neutral PH Con’t K – ionization or dissociation constant Varies from molecule to molecule Show by how much is the ionization or dissociation for acids ka, for bases kb Taking the negative logarithm gives pka, pkb Acid and bases Acids are molecules which Increase H+ concentration Decrease OH- concentration by the same proportion Strong acids - Completely dissociate Weak acids - Partially dissociate Bases are molecules which Increase OH- ion concentration Decrease H+ ion concentration by the same proportion Strong bases - Completely dissociate Weak bases - Partially dissociate  Classify as weak and strong - acid and base Strong Acids Strong Bases – NaOH alkali H2SO4 H2SO4 NaOH Hac HCl Lactic acid H2CO3 Weak Acids Weak Bases H3PO4 Hac NH4OH HCl Lactic acid H2CO3 NH4OH H3PO4 Aspirin Aspirin Con’t All the HCl is assumed to dissociate Thus a 0.001 M solution of HCl has a pH of - log [0.001] = 3 Like wise if we dissolve NaOH in water The pOH is given by the negative log of the concentration of the NaOH The pH is given by 14-pOH (pH + pOH = 14) The pH of a solution of a weak acid is determined not only by the concentration of the acid but also by its pK since it does not completely dissociate Eg acetic acid Henderson-Hasselbalch equation For weak acids and bases The dissociation constant (Ka) of an acid is given by the formula The acidity of the solution is measured by The relationship between pH, pKa, concentration of acid and conjugate base (or salt) is expressed by the Henderson-Hasselbalch equation, Buffers Buffers are solutions which can resist changes in pH when acid or alkali is added Composition of a Buffer Buffers are of two types: Mixtures of weak acids with their salt with a strong base or Mixtures of weak bases with their salt with a strong acid. eg H2CO3/NaHCO3 (Bicarbonate buffer) Con’t Buffer strength or Buffering capacity The buffering efficiency of a weak acid or base is maximal at the pKa of the compound The buffer strength of a solution of a weak electrolyte depends upon two factors The proximity of the pH to the pK of the compound and The concentration of the compound the great the concentration of conjugate acid and conjugate bae the greater the resistance to pH change  ACID-BASE BALANCE Normal pH The pH of plasma is 7.4 (average hydrogen ion concentration of 40 nmol/L). In normal life, the variation of plasma pH is very small. The pH of plasma is maintained within a narrow range of 7.38 to 7.42. The pH of the interstitial fluid is generally 0.5 units below that of the plasma. Acidosis If the pH is below 7.38, it is called acidosis. Life is threatened when the pH is lowered below 7.25. Acidosis leads to CNS depression and coma. Death occurs when pH is below 7.0. Alkalosis When the pH is more than 7.42, it is alkalosis. It is very dangerous if pH is increased above 7.55. Alkalosis induces neuromuscular hyperexcitability and tetany. Death occurs when the pH is above 7.6. Con’t Normal arterial plasma pH is 7.4 The intracellular pH of an erythrocyte is about 7.2 Most other cells are around 7.0 Heavily exercise muscle pH can drop to 6.0 The predominant anions in blood plasma are chloride and bicarbonate and in cytoplasm are phosphates and proteins Intracellular pH is buffered by organic phosphates such as the sugar phosphates pKs 6.5 to 7.6 and protein side chains eg histidine pK 5.6 to 7) Buffers of the body fluids Buffers are the first line of defense against acid load. The buffers are effective as long as the acid load is not excessive, and the alkali reserve is not exhausted. Once the base is utilized in this reaction, it is to be replenished to meet further challenge. Some of the physiological buffers are The bicarbonate buffer The phosphate buffer amino acids and proteins – histidine amino acid in hemoglobin  Con’t The bicarbonate system Blood plasma is buffered in part by the bicarbonate system, consisting of carbonic acid (H2CO3) as proton donor and bicarbonate (HCO3-) as proton acceptor: H + HCO3 H2CO3 - The phosphate buffer system The phosphate buffer system, which acts in the cytoplasm of all cells, consists of H2PO4- as proton donor and HPO42-. H2PO4 H + HPO4 2- Con’t Bicarbonic acid – bicarbonate is an important extracellular buffering system It is largely controlled physiologically rather than chemically CO2 is a gas which is hydrated by carbonic anhydrase in red blood cells to form carbonic acid The concentration of the acid species H2CO3 can be controlled by respiratory regulation ie by breathing rate Operationally CO2 includes both CO2 dissolved and H2CO3 However CO2 dissolved exceeds H2CO3 by 1000 fold at equilibrium The concentration of H2CO3 negligible by comparison Disturbances of acid base balance Classification of Acid-Base Disturbances Acidosis (fall in pH) Respiratory acidosis: Primary excess of carbonic acid. Metabolic acidosis: Primary deficit of bicarbonate Alkalosis (rise in pH) Respiratory alkalosis: Primary deficit of carbonic acid. Metabolic alkalosis: Primary excess of bicarbonate Problem set-1 1. What is the pH of 0.001 M solution of HCl 2. The Ka for a weak acid HAc is 1.6x10-6 What is pH of the acid in a 10-3 M solution Calculate the pKa 3. Given the following H2CO3 = H+ + HCO3- pKa = 6.1 0.03 meq/liter = 1.0 mmHg Normal blood concentration of [HCO3-] and [H2CO3] are 24 meq/lit and 1.2 meq/lit respectively at pH 7.4 Knowing that the pH of blood can drop as low as 6.8 and still be compatible with life, how many meq of acid must be added to plasma to achieve a pH =6.8 Con’t 4. Use the following information for the next series of questions: The pK for CO2/HCO3-system is 6.1; and 0.030 meq/L CO2 =1 mmHg. Remember total [CO2] is assumed to mean the concentration of H2CO3 The blood of an individual who was breathing deeply and rapidly (hyperventilating) was found to have a pH of 7.6 and a PCO2 of 20.7 mmHg Calculate the [HCO3-]/[CO2] ratio in the blood of this individual Calculate the total [CO2] in the blood in meq/L The hyperventilation has produced a condition of respiratory alkalosis. If the total CO2 concentration does not change as the individual resumes normal breathing, what would be the PCO2 in mmHg when the blood returns to a pH of 7.4. Con’t 1. 0.001 M = 10-3 M HCl HCl hydrochloric acid is a strong acid [H+] = 10-3 M PH = - log [H+] = 3 Con’t 2. HAc ↔ H+ + Ac- Ka = [H+][Ac-]/[HAc] Ka = 1.6 x10-6 Pka = - log Ka Pka = - 1.6 x 10-6 Pka = - (- 5.796) Pka = 5.796 [H+] = [Ac-] = X Ka = X2/10-3 1.6 x 10-6 = X2/10-3 X= 4 x 10-5 PH = - log 4 x 10-5 = 4.4 Con’t Con’t 4a. 7.6 = 6.1 + log ([HCO3-]/[CO2]) c. the [HCO3-] can be calculated form the 1.5 = log ([HCO3-]/[CO2]) ratio and [CO2] since the total remains constant [HCO3-]/[CO2] = 31.62 7.4 = 6.1 + log ([HCO3-]/[CO2]) b. pCO2 = 20.7 1.3 = log ([HCO3-]/[CO2]) thus [CO2] =20.7 x 0.030 = 0.621 meq/L ([HCO3-]/[CO2]) = 19.95 therefore [HCO3-] = 31.62 * [CO2] = And [HCO3-] = 19.95 [CO2] 19.64 meq/L Substituting in the equation above for the total [CO2] = [HCO3-] + [CO2] = total CO2 19.64 +0.621 = 20.26 meq/L 19.9[CO2] + [CO2] = 20.26 meq 20.95[CO2] = 20.26 meq. [CO2] = 0.967 meq Or in mmHg pCO2 = 0.967/0.030 = 32 mmHg Causes of acid-base disorders Acidosis Metabolic acidosis – due to increment in endogenous acid Lactic acidosis Can be due to tissue hypo perfusion – circulatory shock Anaerobic metabolism Increased muscle activity Acute lung injury Tissue necrosis in part Ketoacidosis High ketone bodies in diabetes mellitus, starvation and alcoholism Renal failure – Accumulation of organic acids Drugs Particularly aspirin overdose, acetazolamide – carbonic anhydrase inhibition, ammonium chloride Ingestion of poisons – paraldehyde, ethylene glycol, methanol Cont Respiratory acidosis – excess CO2 production and/or inadequate excretion Central hypoventilation – Decreased mental status Excess narcotics Chronic obstructive lung disease – acute exacerbation Acute lung disease like emphysema VQ mismatch – pulmonary embolism Increased CO2 production with fixed ventilation Fever, shivering Cont Alkalosis Metabolic alkalosis vomiting and diarrhea An increased arterial blood PH with an increased strong ion difference and Base excess >2mEq/l Caused by Either by loss of anions or Gain of cations Kidney is usually efficient at regulating the strong ion difference Persistence of metabolic alkalosis usually depends on Either renal impairment Diminished extracellular fluid volume With severe depletion of K+ Resulting in an inability to absorb Cl- in excess of Na+ Cont Respiratory alkalosis Reduction in PCO2 due to increased ventilation Causes Hyperventilation with normal lungs Anxiety, salicylate intoxication Hyperventilation due to hypoxemia Asthma exacerbation Decreased CO2 production with fixed ventilation Hypothermia, chemical paralysis on mechanical ventilation Consequence of acid base imbalance The protons are highly reactive Even in quite low conc Critical influence on a wide variety of biochemical system Biological effect of pH are due to Changes in the ionization of molecules Resulting from protonation or deprotonation Affecting the charge on proteins (enzymes) other critical reactive groups PH Influences the rate of metabolic reactions The behavior of biological membranes Membrane transport systems The binding and transportation of molecules The actions and distribution of drugs Mechanism of Acid base balance The PH of the body is controlled by 3 systems Regulate H+ con in the body fluid Prevent acidosis or alkalosis 1. the chemical acid base buffering By the body fluid that immediately combine with acids or base to prevent excessive changes in pH 2. the respiratory center Regulates the removal of volatile CO2 as a gas in expired air from the plasma Also then regulates the bicarbonate HCO 3- from the body fluids Via pulmornary circulation – the response occurs in minutes 3 the kidney Which can excrete either acid or alkaline urine Adjust the ph of the blood The response takes place over hours or even days But represent a more powerful regulatory system