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Body Fluids
Section A, Group 2
ALFONSO, ALJAMA, ALUZAN
AMURAO, ARELLANO, ARROYO
Water
 Predominant chemical component of living
  organisms
 Universal Solvent
 Has a dipolar structure and exceptional capacity
  for forming hydrogen bonds.
pH Scale
 The acidity of aqueous solutions is generally
  reported using the logarithmic pH scale.
 Bicarbonate and other buffers normally maintain
  the pH of extracellular fluid between 7.35 and
  7.45
pH Scale
Factors for Regulation of Water
Balance
 Depends upon   hypothalamic mechanisms that
  control thirst.
 On Antidiuretic Hormone (ADH)
 Evaporative loss
 Certain diseases like Diabetes Insipidus
Water as an Ideal Biologic
Solvent
Water Molecules form Dipoles
 A water molecule is an irregular, slightly skewed
  tetrahedron with oxygen at its center.
Water Molecules Form Dipoles
 Water is a dipole
 Water, a strong dipole, has a high dielectric
  constant.
 Its strong dipole and high dielectric constant
  enable water to dissolve large quantities of
  charged compounds such as salts.
Water Molecules Form Hydrogen
Bonds
 Hydrogen bonding favors the self-association of
  water molecules into ordered arrays .
Water Molecules Form Hydrogen
Bonds
 Hydrogen bonding profoundly influences the
  physical properties of water and accounts for its
  exceptionally high viscosity, surface tension, and
  boiling point.
 Hydrogen bonding enables water to dissolve many
  organic biomolecules that contain functional
  groups which can participate in hydrogen bonding.
Interaction with Water Influences
the Structure of Biomolecules
Covalent & Noncovalent Bonds
Stabilize Biologic Molecules:
 These forces (covalent and noncovalent   bonds),
  which can be either attractive or repulsive, involve
  interactions both within the biomolecule and
  between it and the water that forms the principal
  component of the surrounding environment.
Hydrophobic Interactions
Electrostatic Interactions
 Interactions between charged groups shape
  biomolecular structure.
 Electrostatic interactions between oppositely
  charged groups within or between biomolecules
  are termed salt bridges.
Van der Waals Forces
 Van derWaals forces arise from attractions
  between transient dipoles generated by the rapid
  movement of electrons on all neutral atoms.
Water is an Excellent
Nucleophile
Water is an excellent nucleophile
 Metabolic reactions often involve  the attack by
  lone pairs of electrons on electron-rich molecules
  termed nucleophiles on electron-poor atoms
  called electrophiles.
 Nucleophiles and electrophiles DO NOT
  necessarily possess a formal negative or positive
  charge.
Water is an excellent nucleophile
 Water, whose two lone pairs of sp3 electrons bear
  a partial negative charge, is an excellent
  nucleophile
 Nucleophilic attack by water generally results in
  the cleavage of the amide, glycoside, or ester
  bonds that hold biopolymers together. This
  process is termed hydrolysis.
 An example of a cleavage of an amide link
Water is an excellent nucleophile
 Conversely, when monomer units are joined
  together to form biopolymers such as proteins or
  glycogen, water is a product.
Water Molecules Exhibit a Slight but
Important Tendency to Dissociate:
 Since water can act both as an acid and as a base,
  its ionization may be represented as an
  intermolecular proton transfer that forms a
  hydronium ion (H3O+) and a hydroxide ion (OH−):
Distribution of Body Water
 Total body fluid is distributed
    between two compartments:

   Extracellular fluid

       interstitial fluid
       blood plasma

   Intracellular fluid
Transcellular Fluid
    small compartment containing body fluids formed by
    the secretion of epithelial cell and is contained within
    epithelial lined spaces

    includes             fluid            in      the
    synovial, peritoneal, pericardial, and intraocular
    spaces, as well as the cerebrospinal fluid

   specialized type of extracellular fluid

   constitute about 1 to 2 liters.
In an average 70-kilogram adult
human:
 Total body  water is about 42 liters or 60 percent of
    the body weight

   This percentage can change depending on:

       Age
       Gender
       Degree of obesity.
Age and Body Fat
Gender and Body Fat
   Women normally have more body fat than men

   They contain slightly less water than men in
    proportion to their body weight
Extracellular and Intracellular Fluid
     cell membrane is semipermeable, only water and
      small, noncharged molecules can move freely
      between interstitial and intracellular compartment.
      Ion can not cross easily.

     All kinds of ionic pump or channel on cell membrane
      determine the uneven distribution
Extracellular and Intracellular Fluid
 ICF and ECF are different   in ionic composition
Intracellular Fluid
    About 28 of the 42 liters of fluid in the body are inside
    the 75 trillion cells

   Constitutes about 40 percent of the total body weight

    Each cell contains its individual mixture of different
    constituents, but the concentrations are similar from
    one cell to another

   Composition of cell fluids is remarkably similar even in
    different animals
Extracellular Fluid
   All the fluids outside the cells

   Account for about 20 percent of the body weight, or about 14 liters in a normal
    70-kilogram adult

    Two largest compartments: (1) interstitial fluid  more than three fourths of
    the extracellular fluid, and (2) plasma  almost one fourth of the extracellular
    fluid, or about 3 liters

   *Plasma - non-cellular part of the blood
         - exchanges substances with the interstitial fluid (pores of the capillary
    membranes)

    Constantly mixing  plasma and interstitial fluids have about the same
    composition except for proteins ( [] in the plasma)
Hypervolemia
 Term used for fluid overload, overhydrated and
  water excess
 It occurs when the body takes in more water than
  it excretes *
 Factors that cause Hypervolemia:
     Cardiac failure
     Renal failure (Kidney’s Damage)
     High sodium intake
     Over infusion of intravenous fluids.
Observations related to fluid
balance
Hypervolemia
 Infants are especially likely to develop
  overhydration (first month of life)*
 For adults, drinking too much water rarely causes
  overhydration when the body's systems are
  working normally
 Brain- the organ most vulnerable to the effects of
  overhydration*
Hypervolemia
Effects of Hypervolemia
Hypervolemia
   Treatment
     Limit fluidintake
     In more serious cases, diuretics may
      be prescribed to increase urination
     Identifying and treating any
      underlying condition (such as
      impaired heart or kidney function) is a
      priority
Hypervolemia
 NOTE:
    The best advice is to drink when you are thirsty and
     to aim to drink 6-8 glasses, 2-3 litres per day;
    *Consider the differences in physical
     activity, climate and diet
    *Less fluid intake for lower intensity exercise in
     milder conditions and more for superior athletes
     competing at higher intensities in warmer
     environments
Hypervolemia
• The best guidance is
    for individuals to
   remain adequately
    hydrated, but not
      overhydrated
Calculate your water needs:
Water Homeostasis
 The average adult body
  contains 40 liters of H2O.
  This amount, called total
  body water, remains
  fairly constant under
  normal circumstances.
Maintenance of Water Homeostasis
 It is a balancing act
  because the amount
  of water taken in must
  equal the amount of
  water lost.
Disturbance of Water Homeostasis
   Two categories
   Gain or loss of
    Extracellular fluid
    volume
   Gain or loss of solute
   In many instances
    disturbances of water
    and homeostasis involve
    imbalances of both
    volume and solute.
Mechanism of Fluid Balance
 Antidiuretic Hormone
 Thirst mechanism
 Aldosterone
 Sympathetic Nervous System
Effect of ADH
Thirst mechanism
 The prime regulator of water intake and involves
  hormonal and neural input as well as voluntary
  behaviors.
WATER AND ELECTROLYTE
BALANCE & BODY FLUIDS
Electrolytes
 Cations
 Anions
 Electrolytes are not evenlydistributed within the
  body, and their uneven distribution allows many
  important metabolic reactions to occur
Purpose of Electrolytes
 Help control water balance and fluid distribution
  in the body
 Create an electrical gradient across cell
  membranes that is necessary for muscle
  contraction and nerve transmission
 Regulate the acidity (pH) of the blood
 Help regulate the level of oxygen in the blood
 Are involved in moving nutrients into cells and
  waste products out of cells
Specific Function
 Sodium- affects how much urine the kidney
  produces and is involved in the transmission of
  nerve impulses and muscle contraction
 Potassium- regulate fluid balance in cells, the
  transmission of nerve impulses, and in muscle
  contractions
 Calcium-build and maintain bones. It also plays a
  role in nerve impulse transmission and muscle
  contraction.
Specific Function
 Magnesium- involved   in protein synthesis and
  cellular metabolism
 Chloride- involved in regulating blood pressure
 Phosphate- helps control the acidity level (pH) of
  the blood; also causes calcium to be deposited in
  bones
Electrolyte Balance
Body Secretions
Gastrointestinal Secretions
Saliva (Composition)
    Inorganic composition  dependent on stimulus and rate of salivary
    flow

       Major components are Na+, K+, HCO3-, Ca++, Mg++, and Cl-.

       [] of ions varies with the rate of secretion  which is stimulated during the
        postprandial period.

   Organic constituents  synthesized, stored, and secreted by the
    acinar cells

       Major products are amylase, lipase, glycoprotein (mucin, which forms mucus
        when hydrated), and lysozyme (attacks bacterial cell walls to limit
        colonization of bacteria in the mouth)
Saliva (Enzyme Content)
   2 major types of protein secretion:

    Serous secretion  contains ptyalin, an amylase
    enzyme for digesting starches and cleansing agent for
    the oral cavity

   *Saliva has a pH between 6.0 and 7.0 (favorable range
    for the digestive action of ptyalin)

   Mucus secretion  contains mucin for lubricating and
    for surface protective purposes
Saliva (Enzyme Content)
   Parotid glands - serous type of secretion

  Submandibular and Sublingual glands - both serous
secretion and mucus

   Buccal glands - secrete only mucus

 *Aside from amylase, saliva has presence of other enzymes
such as maltase, catalase, lipase, urease, and protease.
Saliva (Control Mechanism)
Saliva (Control Mechanism)
   Salivary    glands          controlled      mainly by
    parasympathetic nervous signals, from the superior
    and inferior salivatory nuclei in the brain stem

   Salivatory nuclei  excited by both taste and tactile
    stimuli from the tongue, mouth and pharynx

   *  salivation  taste stimuli, especially sour taste
    (caused by acids), tactile stimuli, such as the presence
    of smooth objects in the mouth
Saliva (Control Mechanism)
 Salivation can be stimulated or inhibited by
  nervous signals arriving in the salivatory nuclei
  from CNS

 Appetite  area of the brain  located in proximity
  to the parasympathetic centers of the anterior
  hypothalamus, functions to in response to signals
  from the taste and smell areas of the cerebral
  cortex or amygdala.
Saliva (Control Mechanism)
   Saliva  helps remove the irritating factor in the GIT
    (diluting or neutralizing the irritant substances)

   Sympathetic nerves  from Superior cervical ganglia
     Salivary glands (slight increase in salivation)

   2 factor - blood supply to the glands (nutrition)

   Parasympathetic nerve signals  copious salivation 
    moderately dilate the blood vessels  increased
    salivatory gland nutrition
Saliva (Functions)
   Digestive function (enzymes)

   Moistens and lubricates food  swallowed easily

    Holds the taste-producing substances  brings in
    contact with the taste buds

    Dilutes salts, acids  protecting the mucosa
    (teeth)
Saliva (Function on Oral Hygiene)
    Under basal awake conditions  about 0.5 ml/ min of saliva (mucous
     type)
    *During sleep, secretion becomes very little.

    Saliva helps prevent deteriorative processes in several ways:

1.   Wash away pathogenic bacteria and food particles that provide their
     metabolic support
2.    Contains thiocyanate ions and lysozyme
3.   Contains protein antibodies that can destroy oral bacteria, including
     some that cause dental caries

    *In the absence of salivation, oral tissues  often become ulcerated
     and infected  caries of the teeth can become rampant.
Saliva (Tests)
   Saliva is easy to access and collection is non-invasive

    Used to identify individuals with disease (presence of biomarkers) and
    to monitor progress under treatment

    Viral infections such as human immunodeficiency virus
    (HIV), herpes, hepatitis C, and Epstein-Barr virus infection 
    polymerase chain reaction (PCR) techniques

   Bacterial infections, such as Helicobacter pylori, can likewise be
    detected in saliva

   Monitoring drugs levels
Saliva (Clinical Disorders)
   *Abnormal production of the salivary glands can cause
    serious complications & adverse effects to salivary
    functions.

    Xerostomia (dry mouth) is caused by impaired salivary
    secretion

   Congenital or develop as part of an autoimmune process

    Decrease in secretion  reduces pH in the oral cavity 
    tooth decay and is associated with esophageal erosions 
    difficulty swallowing.
Gastric Juice
   Stomach mucosa has two important types of tubular glands: (1)
    oxyntic glands (gastric glands) and (2) pyloric glands.

    Oxyntic (acid-forming) glands - secrete HCL, pepsinogen,
    intrinsic factor, and mucus

        3 types of cells: (1) mucous neck cells (mucus); (2) peptic or chief
        cells (pepsinogen); and (3) parietal or oxyntic cells (hydrochloric
        acid and intrinsic factor)

   Pyloric glands - secrete mainly mucus (protection of the pyloric
    mucosa from the stomach acid) and hormone gastrin.
Composition: Inorganic Constituents
    Secretory rate  Higher the concentration of ions

    [K+] is always higher in gastric juice than in plasma
    (prolonged vomiting may lead to hypokalemia).

   At high rates of secretion, gastric juice resembles an
    isotonic solution of HCl

   Gastric HCl converts pepsinogens to active pepsins and
    provides the acid pH at which pepsins are active
Composition: Inorganic Constituents

    Rate of gastric H+ secretion varies considerably among
    individuals

   Basal (unstimulated) rates of gastric H+ production  1 to 5
    mEq/hr

   During maximal stimulation, HCl production  from 6 to 40
    mEq/hr

    Total number of parietal cells in the stomach  partly
    responsible for the wide range in basal and stimulated rates
    of HCl secretion.
Gastric Juice

Composition: Organic Constituents




       Pepsin  proteases secreted by the chief cells, active at pH 3
      & below

      Pepsinogen  the inactive proenzyme of pepsin

       Pepsinogens
                 - contained in membrane-bound zymogen granules in
      the chief cells
                 - converted to active pepsins by the cleavage of acid-
      labile linkages (the lower the pH, the more rapid the conversion)
Gastric Juice

Enzyme Content

  Pepsin

   Pepsinogen - no digestive activity, activated to pepsin when comes
  in contact with HCL

   Pepsin - proteolytic enzyme (optimum pH 1.8 to 3.5), above pH 5 
  almost no proteolytic activity (inactivated)

   Major products of pepsin action  large peptide fragments and
  some free amino acids

   Gastric protein digestion  important in peptides and amino acids
  generation  stimulants for cholecystokinin release in the duodenum

  * Gastric peptides are therefore instrumental in the initiation of the
  pancreatic phase of protein digestion
Gastric Juice

Enzyme Content



  Gastric Lipase

   Initiating the digestion of lipids in the stomach.

   Converts triacylglycerols into fatty acids and diacylglycerols

   Initial hydrolysis  important since some of the water-immiscible
  triacylglycerols are converted to products with both polar and non-
  polar groups (stable interface with the aqueous environment)
Gastric Juice
Control Mechanism: SECRETION
   Gastric secretion occur in three phases: (1) cephalic phase, (2) gastric
   phase, and (3) intestinal phase
Gastric Juice

Control Mechanism


  Cephalic phase

   Occurs even before food enters the stomach, especially while it is
  being eaten

   Results from the sight, smell, thought, or taste of food, and the
  greater the appetite, the more intense is the stimulation

   Neurogenic signals originate in the cerebral cortex and appetite
  centers of the amygdala and hypothalamus  transmitted through the
  dorsal motor nuclei of the vagus  vagus nerves to the stomach
Gastric Juice

Control Mechanism


  Gastric phase

   Once food enters the stomach  excites the long vagovagal reflexes
  from the stomach to the brain and back to the stomach  local enteric
  reflexes  gastrin mechanism  cause secretion of gastric juice
  during several hours while food remains in the stomach

   Accounts for about 70 per cent of the total gastric secretion
  associated with eating a meal (1500 ml).
Gastric Juice

Control Mechanism


  Intestinal phase

  Presence of food in the upper portion of the small intestine
  (duodenum)  cause stomach secretion of small amounts of gastric
  juice (partly because of small amounts of gastrin released by the
  duodenal mucosa)
Gastric Juice

Control Mechanism: INHIBITION


   Affected by other post-stomach intestinal factors

        Presence of food in the small intestine  reverse enterogastric
       reflex  transmitted through the myenteric nervous
       system, extrinsic sympathetic and vagus nerves  inhibits
       stomach secretion

        Can be initiated: distending the small bowel, presence of acid
       (upper intestine), presence of protein breakdown products, or by
       irritation of the mucosa

        This is part of the complex mechanism for slowing stomach
       emptying when the intestines are already filled.
Gastric Juice

Control Mechanism: INHIBITION


   Release of several intestinal hormones

        Secretin - important for control of pancreatic secretion but
       opposes stomach secretion
        Gastric inhibitory peptide, vasoactive intestinal polypeptide, and
       somatostatin - slight to moderate effects in inhibiting gastric
       secretion

   Functional purpose of inhibitory gastric secretion: to slow passage
  of chyme from the stomach when the small intestine is already filled
  or already overactive

   Enterogastric inhibitory reflexes plus inhibitory hormones also
  reduce stomach motility at the same time that they reduce gastric
  secretion
Gastric Juice

Functions


    Gastric juice is characterized by the presence of hydrochloric acid
   and therefore a low pH less than 2 as well as the presence of proteases
   of the pepsin family

    Acid serves to kill off microorganisms and also to denature proteins

   *Denaturation makes proteins more susceptible to hydrolysis by
   proteases

    Serves in the initial hydrolysis of lipids with the help of gastric
     lipase enzyme
Gastric Juice

Tests


    Qualitative tests include those for butyric acid, lactic acid, occult
   blood, bile and trypsin.

         Presence of the first two acids  yeast or other microorganisms
        in the gastric secretions  lack of hydrochloric acid
         If blood is present  ulcers, hemorrhages and other pathologic
        states
         Either bile or trypsin  evidence of regurgitation of intestinal
        contents

    Quantitative procedures  total acidity contributed by HCL, organic
   acids and acid salts, neutralized or buffered by various constituents of
   the gastric juice and food
Gastric Juice

Clinical Disorders



    Achlorhydia - absence of hydrochloric acid (pernicious anemia, gastric
   carcinoma)

    Hypoacidity - if HCL is not entirely absent but below normal
   (pregnancy, gastric carcinoma, gastritis and constipation, secondary
   anemia, and chronic debilitative diseases)

    Hyperacidity - acidity is elevated (duodenal ulcer and gallbladder
   disease)

   *It should be emphasized that the acidity cannot exceed a certain value
   (pH 0.87) since the parietal cells secrete a fluid of constant composition
Pancreas
Pancreatic Juice


  The pancreas, parallel to and beneath the stomach, is a large
 compound gland similar to the internal structure of salivary glands

  Exocrine secretion: combined product of enzymes and sodium
 bicarbonate secretions  flows through a long pancreatic duct  joins
 the hepatic duct  empties into the duodenum through the papilla of
 Vater, surrounded by the sphincter of Oddi.

  The pancreas also secretes insulin (not secreted by the same
 pancreatic tissue secreting pancreatic juice)

  Insulin is secreted directly into the blood—not into the intestine—by
 the islets of Langerhans that occur in islet patches throughout the
 pancreas
Pancreatic Juice

Composition



   Alkaline in nature with a pH of about 8.

   Large volumes of sodium bicarbonate solution are secreted by the
  small ductules and larger ducts leading from the acini

   Bicarbonate ions play an important role in neutralizing the acidity of
  the chyme emptied from the stomach into the duodenum.

   The pancreatic digestive enzymes are secreted by pancreatic acini
Pancreatic Juice

Enzyme Content



   Pancreatic secretion contains multiple enzymes for digesting all of the
  three major types of food: proteins, carbohydrates, and fats

  Proteins:

   Trypsin and chymotrypsin  split whole and partially digested
  proteins into peptides of various sizes (do not cause release of individual
  amino acids)

   Carboxypolypeptidase  split some peptides into individual amino
  acids  completing digestion of some proteins all the way to the amino
  acid state
Pancreatic Juice

Enzyme Content



   Proteolytic   digestive  enzymes     -   inactive   forms    first:
  trypsinogen, chymotrypsinogen, and procarboxypolypeptidase

   Activated after secreted into the intestinal tract

   Trypsinogen  activated by an enzyme called enterokinase (secreted
  by the intestinal mucosa when chyme comes in contact with it) or by
  previously activated trypsin

   Chymotrypsinogen and Procarboxypolypeptidase  activated by
  trypsin to form chymotrypsin and carboxypolypeptidase
Pancreatic Juice

Enzyme Content


  Carbohydrates:

   Pancreatic amylase  which hydrolyzes starches, glycogen, and most
  other carbohydrates (except cellulose)  form mostly disaccharides and
  a few trisaccharides

  Fat:

   Pancreatic lipase  hydrolyzing neutral fat into fatty acids and
  monoglycerides

   Cholesterol esterase  hydrolysis of cholesterol esters

   Phospholipase  splits fatty acids from phospholipids
Pancreatic Juice

Control Mechanism


  3 Basic stimuli for pancreatic secretion

   Acetylcholine  released from the parasympathetic vagus nerve
  endings and from other cholinergic nerves in the enteric nervous system

   Cholecystokinin  secreted by the duodenal and upper jejunal
  mucosa when food enters the small intestine

   Secretin  secreted by the duodenal and jejunal mucosa when
  highly acid food enters the small intestine
Pancreatic Juice

Control Mechanism


   Acetylcholine and cholecystokinin  stimulate the acinar cells of the
  pancreas  production of large quantities of pancreatic digestive
  enzymes (relatively small quantities of water and electrolytes)

  *Without water, most of the enzymes remain temporarily stored in the
  acini and ducts until more fluid secretion comes along to wash them into
  the duodenum

   Secretin  stimulates secretion of large quantities of water solution
  of sodium bicarbonate by the pancreatic ductal epithelium
Regulation of Pancreatic Secretion
Pancreatic Juice

Control Mechanism


  Pancreatic secretion occurs in three phases: (1) cephalic phase, (2)
  gastric phase and (3)intestinal phase

  Cephalic phase  same nervous signals from the brain that cause
  secretion in the stomach  cause acetylcholine release by the vagal
  nerve endings in the pancreas  causes moderate amounts of enzymes
  to be secreted into the pancreatic acini

  *Accounting for about 20 per cent of the total secretion of pancreatic
  enzymes after a meal
Pancreatic Juice

Functions



   Secretions from pancreas  quantitatively the largest contributors to
  enzymatic digestion of food

   Provides additional important secretory products that are vital for
  normal digestive function including

   Water and bicarbonate ions  neutralizing gastric acid so that the
  small intestinal lumen has a pH approaching 7.0.  reduces injury to
  small intestinal mucosa by such acid acting in combination with pepsin

  *Pancreatic enzymes are inactivated by high levels of acidity
Pancreatic Juice

Tests


   The fact that secretin stimulates the flow of pancreatic juice has been
  made use as a test of external pancreatic functions

   Double-lumen tube  passed (longer end reaches the third portion of
  the duodenum and the shorter end remains in the stomach) 
  continuous aspiration (-20 to 30 mmHg) prevents the overflow of gastric
  juice into the duodenum and sucks out both gastric juice and duodenal
  contents into separate containers  secretin is injected intravenously
  after a basal flow has been obtained  volume of flow and bicarbonate
  concentration is measured
Pancreatic Juice

Tests


   Outpouring of pancreatic juice

         Under normal conditions, duodenal fluid  lose its biliary color
         If the bile color remains  a non-functioning gallbladder is
        indicated
         The total volume varies normally from 135 to 250 ml in 1 hour,
        and the bicarbonate, from 90 to 130 mEq

  *In pancreatitis with extensive destruction of parenchymal structures,
  there is usually a diminution in the volume of pancreatic juice and
  bicarbonate output
Pancreatic Juice

Clinical DIsorders


   Damaged pancreas/ ducts blocked  large quantities of pancreatic
  secretion become pooled in the damaged areas

   Pancreatitis  enzymes secreted by pancreatic acinar cells become
  proteolytically activated before reaching appropriate site of action (small
  intestinal lumen)

        Pancreatic juice contains trypsin inhibitors  reduce the risk of
       premature activation

        Trypsin can itself be degraded by other trypsin molecules

  *Specific mutation in trypsin  renders it resistant to degradation by
  other trypsin molecules.
Pancreatic Juice

Clinical DIsorders


   Pancreas reacts very sensitively to an impairment of the protein
  metabolism

        Decreased supply of proteins leads  impairment of the
       endogenous stimulation of pancreas  atrophy of acinous cells
       and fibrosis of pancreas (e.g. long-term fasting)

  Decreased contents of pancreatic enzymes

        Decreased secretion of their proenzymes, insufficient intraluminal
       activation or inactivation of enzymes

  *Celiac sprue  secretions of lipase and trypsinogen are decreased 
  trypsin deficiency  deficiency of chymotrypsin and other enzymes
  which are activated from proenzymes by trypsin
BILE
 An alkaline, brownish-
  yellow or greenish-yellow
  fluid that is secreted by the
  liver, stored in the
  gallbladder, and discharged
  into the duodenum and aids
  in the
  emulsification, digestion, an
  d absorption of fats.
Bile Composition
 Water (85%),
  bile salts
  (10%),(Cholic, chenodeoxycholic, deoxycholi
  c, and lithocholic acid)
  mucus
• pigments (3%), bile pigments e.g bilirubin
  glucuronide
• fats (1%), such as Phospholipids (lecithin)
  , cholesterol
• 0.7% inorganic salts
Bile Composition
 In concentrating process in gallbladder, water and
  large portions of electrolytes are reabsorbed by
  gallbladder mucosa
 Bile salts and lipid substances cholesterol and
  lecithin, are not reabsorbed
 The concentrated bile is composed of bile salts,
  cholesterol, lecithin, and bilirubin.
Bile Pigments

 Bilirubin and Biliverdin*




Urobilin     Urobilinogen     Bilirubin   Biliverdin
(Brown)       (colorless)      (red)       (green)
Bile Secretion
  Release of hormone
                                     Bile is subsequently
    secretin and CCK
                                  stored & concentrated in
(chocystokinin) from the
                                  the gallbladder between
duodenum increase bile
                                              meals
        secretion




                   Bile is normally stored in
                   gallbladder until needed
                         in duodenum*
Bile Secretion
 After meal, bile enters the duodenum    as a result
  of combined effects of :
     Gall bladder emptying
     Increased bile secretion by liver
 The amount of bile secreted per day ranges from
  250 ml to 1 litre
Emptying of Gallbladder
 Gallbladder begins to
empty, when food (fatty           Gallbladder emptying is
    foods) reach the             rhythmical contractions of
  duodenum about 30                   the gallbladder*
 minutes after a meal*




                     Effective emptying
                   requires simultaneous
                 relaxation of sphincter of
                            oddi*
Bladder bile vs. Liver bile bile (%)
Constituent         Bladder bile (%) Liver

Water                   82.3-89.8    96.5-97.5

Solids                  10.2-17.7    2.5-3.5

Bile Salts              5.7-10.8     0.9-1.8

Mucus and Pigments      1.5-3.0      0.4-0.5

Cholesterol and other   0.5-4.7      0.2-0.4
lipids


Inorganic Salts         0.6-1.1      0.7-0.8
ENTEROHEPATIC CIRCULATION
               About 95% of the salts
                secreted in bile are
                reabsorbed actively in the
                terminal ileum and re-used.
                Blood from the ileum flows
                directly to the hepatic
                portal vein and returns to
                the liver where the
                hepatocytes reabsorb the
                salts and return them to the
                bile ducts to be re-
                used, sometimes two to
                three times with each meal.
Function of Bile Juice*
 Bile  acts as a surfactant , helping to emulsify the
  fats in the food.
 Bile salt anions have a hydrophilic side and a
  hydrophobic side, and therefore tend to aggregate
  around droplets of fat ( triglycerides and
  phosphiolipids ) to form micelles.
 The hydrophilic sides are positively charged due to
  the lecithin and other phospholipids that compose
  bile, and this charge prevents fat droplets coated
  with bile from re-aggregating into larger fat particles.
 Fat in micelles* form provide a large surface area for
  the action of the enzyme pancreatic lipase in the
  digestion of lipids.
Bile Juice
Function of Bile Juice
 The alkaline bile   has the function of neutralizing
  any excess stomach acid before it enters the
  ileum.
 Bile salts also act as bactericides, destroying many
  of the microbes that may be present in the food.
Preventing Metabolic Deficit
 Without  the presence of bile salts in the intestinal
 tract, up to 40 percent of the ingested fats are lost
 into the feces, and the person often develops a
 metabolic deficit because of this nutrient loss.
Abnormalities associated with bile
 Gall stone- majority of gall
  stones are made up of
  cholesterol , (cholesterol
  tends to accrete into lumps
  in the gallbladder)
 Causes of gall stones;
 - Too much absorbtion of
  water from the bile .
 - Too much cholesterol in
  bile.
 - Inflammation of the
  epithelium.
Small intestine juice
 small intestine is where most chemical digestionand fluid
  absorption takes place
 Water and lipids are absorbed by passive diffusion throughout
  the small intestine.
 Sodium Bicarbonate is absorbed by active transport and
  glucose and amino acid co-transport
 Fructose is absorbed by facilitated diffusion
Intestinal Juice
 Intestinal juice is not as
  definite an entity as
  pancreatic juice or gastric
  juice because it varies at
  different levels of intestinal
  tract*
 Succus entericus is
  influenced by the hormone
  secretin
 Enterocrinin* stimulates
  mucosal glands
Intestinal Juice*

 leukocytes    Epithelial cells       Mucus



                                  Organic material
  1.5% Solid
                  8.3 pH*         eg. mucoproteins
components*
                                    and enzyme*
Feces Formation and Composition
Feces is the waste material
  passed out from the bowels
  through the anus.

    It is usually solid to semi-
    solid in consistency but can
    be hard in constipation or
    watery with diarrhea
Feces Formation
 Large amounts of water and electrolytes are
  absorbed in the first half of colon.*
 Water absorption transforms the fluid chyme into
  a mush-like consistency by the time it passes
  through the transverse colon.
 It solidifies further along its passage down the
  descending colon.
Composition of Feces
 About 75% of fecal weight is made up of water.
 The other 25% is composed of solid matter which
  contains :
      Undigested fiber and solidified components of
      digestive juices (30%)
     Bacteria (30%)
     Fat (10% to 20%)
     Inorganic matter (10% to 20%)
     Protein (2% to 3%)
Water and Electrolytes in the Colon
 Electrolytes(bicarbonate) are secreted by the wall
  of the large intestine into the lumen to neutralize
  any acidic byproducts of bacterial metabolism.
 Sodium and chloride are absorbed by the
  intestinal wall which creates a concentration
  gradient to facilitate water absorption.
Feces
 *Any extra fluid remain in the colon give a liquid
  consistency to the feces (loose stool).
 It also increases defecation frequency by
  triggering the local defecation reflex.
Feces
 The Bristol Stool Chartor Bristol Stool Scale is a
  medical aid designed to classify the form of
  human feces into seven categories

  The form of the stool depends on the time it
  spends in the colon.
Color of feces
 Feces usually has a brown color, ranging from a
  tan hue to a darker-brown color.
 Bilirubin is passed out in the bile and the action
  of bacteria and air in the gut breaks it down into
  stercobilin and urobilin, which gives stool its
  typical color.
Smell of Feces
   Odor
      - H2S (rotten egg smell)
      - mercaptans (sewer gas)
Characteristics

Characteristics of urine under physiological conditions
        Characteristic         Normal Quantity or Quality
           Volume               115 to 180 L /day (women)
                                 130 t0 200 L / day (men)
            Color                         Amber
            Odor                Not unpleasant (aromatic)
          Turbidity               Clear and transparent
             pH                          4.6 to 8.0
 Color                              Odor
     Amber                             Does not have unpleasant
     Pigment: urochrome                 smell (aromatic)
     Other            pigments:        Other odors arise from food
      uroerythrin, uroporphyrins,       Mercaptan-like odor after
      riboflavin                         eating asparagus
                                        Oil of wintergreen (has
                                         methyl salicylate)  strong
                                         odor of evergreens
 Turbidity                         pH
     Urine      is    clear and       Varies from 4.6 to 8.0
      transparent                      Protein diet gives rise to
     After standing for a long         acidic pH  oxidation of
                                        sulfur in sulfur containing
      time  flocculent material        amino acids into sulfuric
      (mucoprotein             +        acid
      nucleoprotein + epithelial       Vegetable and fruit diet
      cells) separates                  gives rise to alkaline urine
                                       Urine samples taken right
                                        after eating meals are
                                        alklalinesecretion of H+ in
                                        the gastric juice
Ions in the urine
 Anions                                Cations
     The major anion is chloride           Sodium and potassium are
     The amount is equal to the             the major cations
      amount that was ingested              Total excretion of Na+ varies
     In salt-poor diets, Cl- may be         between 2.0 and 4.0 g/day
      absent                                K+ 1.5 to 2.0 g/day.
   Nitrogenous organic
    compounds                         Component       Amount
     Urea α the total nitrogen       Urea            12 to 36 g per
      intake                                          day (70-g
     Uric acid – end product of                      adult)
      purine metabolism; α purine     Uric acid       0.7 g of uric
      intake                                          acid per day
     Creatinine α muscle mass
                                      Creatinine      18 to 32 and
     Creatine    predominant in      (coefficient)   10 to 25 in
      children     and    pregnant                    women
      women
                                      Hippuric acid   0.7 g per day
     Hippuric acid - formed in the
      liver                           Indican         5 to 25 mg per
     Indican – potassium salt                        day
Composition
Normal concentration of organic compounds, anions, and cations in urine
  Component       Concentration in   Concentration in            [U]/[P]*
                 urine (mg percent) blood (mg percent)
     Urea               2000                30                     67
   Uric acid             60                  2                     30
  Creatinine             75                  2                     37
   Indican               1                 0.05                    20
  Phosphate             150                  3                     50
    Sulfate             150                  3                     50
  Potassium             150                 20                     7.5
   Chloride             500                350                     1.4
   Sodium               350                335                      1
   Calcium               15                 10                     1.5
      * Concentration in urine / concentration in blood plasma
Glycosuria
 The normal glucose range is 10 to 20 mg per 100
  mL or urine
 High amounts of sugars lead to glycosuria
     Glucosuria
     Pentosuria
     Lactosuria
     Galactosuria
     Fructosuria
 Pentosuria                             Tests for pentosuria
     Occurs after eating unusual            Benzidine + acetic acid +
      amounts of fruits and fruit             urine  mixture is heated
      juices                                  then cooled  rose-pink
     Idiopathic pentosuria –                 color (+ for pentose)
      occurs in the absence of L-            (+) Benedict’s reagent
      xylulose dehydrogenase (a              (-)       baker’s      yeast
      genetic disease)                        fermentation
       Xylulose is   excreted in the
        urine
 Lactosuria                           Tests for lactosuria
     Moderate amounts of                  (+)       baker’s     yeast
      lactose secretion is found in         fermentation
      lactating women                      (+) mucic acid test
       Does not occur in pregnancy
                                           (-) Barfoed’s test
                                           Yields lactosazone
 Fructosuria                          Tests for fructosuria
     Occurs in association with           (+) Benedict’s reagent
      diabetes mellitus                    (+)       baker’s      yeast
     The site of difficulty is the         fermentation
      liver (it’s where fructose is        Yields glucosazone and
      stored as glycogen                    phenylhydrazine
     There is a deficiency in the
      enzyme fructokinase
 Galactosuria                       Tests for galactosuria
     A      consequence       of        reduction of alkaline copper
      galactosemia                        solutions
     Galactose is not detectable        slight fermentation by
      in the urine prior to the           baker’s yeast
      introduction of milk in the        (+) Barfoed’s test
      diet                               (+) mucic acid test.
 Proteinuria                       Tests for Proteinuria
     presence of proteins, most        Nitric acid ring test
      especially albumin, in the        Sulfosalicylic acid test –
      urine.                             degree of turbidity (+)
     Plasma proteins may pass          Heat and acetic acid test –
      damaged renal epithelium           ring of white turbidity (+)
   Lipuria
       presence of large amounts of
        fat in the urine
       Urine is opalescent, turbid, or
        milky when voided
       The high blood fat (lipemia)
        that sometimes occurs in
        diabetes mellitus and lipoid
        nephrosis may lead to lipuria.
       Also in patients with fractures
        of the long bones with injury
        to the bone marrow
Lymph
Body Fluid
 The lymphatic system maintains volume
 and pressure of the extracellular fluid
  returns excess water and dissolved substances
   from the interstitial fluid to the circulation
 Lymph   is the fluid that is present in the
 lymphatic capillaries that drain the
 interstitial spaces.
Mechanism of lymph flow
 Travels   down the pressure
  gradient.
 Muscular and respiratory
  pumps push the lymph
  forward via the action of
  semilunar valves.
 blood       capillaries  
  interstitial fluid  lymph
  capillaries  lymphatic
  veins  lymph nodes 
  lymph ducts and finally 
  brachiocephalic veins and
  vena cavae.
Composition
 Lymph has a similar composition to blood
 plasma.
  The  only difference is that it contains lower
   percentage of protein than blood plasma.
  Lymph     albumin:globulin ratio > plasma
   albumin:globulin ratio
    Albumin is smaller than globulin  it diffuses
     from plasma to lymph more readily than the
     latter.
  Fibrinogen, prothrombin, and leukocytes are
   present in lymph, too.
 The composition of lymph varies with the
 state of digestion.
     After a meal, the fat content rises since more than
      half the fat absorbed goes by this route. The lymph
      becomes milky if the food contains much fat.
 Lymph has the same composition as the ISF
 Asit flows through the lymph nodes it comes
 in contact with blood, and tends to
 accumulate               more             cells
 (particularly, lymphocytes) and proteins.
 Anedema that is caused by
 the blockage of lymph
 return
Cerebrospinal fluid
Body Fluids
CSF functions   in
  protecting the brain from sudden
   changes in pressures.
  Maintaining a stable environment
  removing waste products of the cerebral
   hemisphere.
Production of CSF
choroid plexus    P                  P
                                         subarachnoid
    in the             cisternae
                                            space
  ventricles




arachnoid villi       venous blood
Characteristics of CSF under physiological conditions

      Characteristic            Normal Quantity or
                                     Quality
         Volume                   20 mL per day
           Color                      Colorless
      Specific gravity             1.004 to 1.008
         Turbidity                     Clear
            pH                      7.35 to 7.40
Component         Concentration or ratio in CSF

    Glucose                 <4.5 mmol/L

    Lactate                 <2.1 mmol/L
    Proteins              0.15 to 0.45 g/L
IgG (blood to CSF              500:1
      ratio)
    IgG index                   0.66
CSF Pathology
   Spinal cord disorders (compressive syndrome)
   Hemorrhage
   Infections (meningitis, encephalitis, myelitis)
   Inflammatory autoimmune diseases (multiple
    sclerosis, Guillain-Barré syndrome)
   Systemic autoimmune diseases (vasculitis, systemic lupus
    erythematosus)
   Malignancy
   Degenerative processes (Alzheimer’s
    syndrome, amyotrophic lateral sclerosis, Parkinson’s
    disease)
   Demyelinating disease
 CSF is collected using lumbar puncture. The
  appearance and pressure of CSF are evaluated to
  know what kind of pathology is present in an
  individual.
Lange’s colloidal
gold test
 Done     by      mixing
 decreasing dilutions of
 CSF with colloidal gold
 solution
    Normal CSF causes no
     change in the appearance
     of the orange-red colored   • Paretic curve
     solution                      • Fluids with large globulin
    Fluids with pathologic          content
     conditions produce color      • Such curves are contained in
     change depending on the         casese with general paralysis
     condition and dilutiona       • Multiple    sclerosis,   lead
                                     poisoning      with     brain
                                     involvement
 Luetic curve                          • Meningitic curve
     Fluids with limited globulin        • Large amounts of globulin and
      and moderate albumin content          globulin
     Certain forms of cerebro-spinal     • All meningitic conditions show
      syphilis                              this kind of curve
     Also           in         brain
      tumor, poliomyelitis, and
      cerebral arteriosclerosis
Sperm & Semen (Contents)
   Fructose – this serves as the primary nutrient source
    of the sperm cells.

   Citric Acid – no definite function for the sperm. But is a
    basis for diagnosing acute and chronic prostatitis

   Fibrinogen – forms a clot when the semen is
    introduced to the reproductive tract, forms a clot for
    15 mins then disintegrates to promote sperm motility.
 Prostaglandins – makes the female reproductive
  tract more receptive to sperm movement and
  possibly causes backward, reverse peristaltic
  movement to propel the sperm towards the
  ovaries. (A sperm cell can reach the upper ends of
  the fallopian tube within 5 minutes)
 Profibrinolysin – is changed to fibrinolysin to
  dissolve the clot formed by the fibrinogen
 Calcium ion – enters the sperm when it is within
  the female reproductive tract thus giving the
  sperm a whiplash motion.
Contained in the acrosome
 Hyaluronidase – depolymerizes the hyaluronic
  acid polymers in the intercellular cement that
  holds the ovarian granulosa cells together.

 Proteolytic enzymes – digest proteins in the
  structural elements of tissue cells that still adhere
  to the ovum
 The Prostate glands secretes a thin milky fluid   that
  contains calcium, citrate ion, phosphate ion, a
  clotting enzyme and profibrinolysin.
 Alkalinic pH is to combat the Acidic pH of the
  vagina (pH of 3.5 to 4.0). The sperm becomes
  motile when the pH rises to about 6.0 to 6.5.
Control Mechanism
 Spermatogenesis
 Testosterone, secreted by the Leydig cells,
  essential for growth and division of the testicular
  germinal cells, first stage in forming sperm cells.
 Luteinizing hormone, stimulate the Leydig cells to
  release testosterone
Control Mechanism
 Follicle-stimulating hormone, stimulates the
  Sertoli cells; without this stimulation, the
  conversion of the spermatids to sperm will not
  occur.
 Estrogens, essential for spermiogenesis
 Growth hormone, promotes early division of the
  spermatogonia
Diagnostic Procedures
 Semen Allergy Test -  Women with seminal plasma
  protein allergy (SPPA) have an immunologic
  response to human semen. The immunological
  mechanism of semen allergy is a type I
  hypersensitivity reactions.
 Semen Analysis - A low sperm count is diagnosed
  as part of a semen analysis test. Sperm count is
  generally determined by examining semen under
  a microscope to see how many sperm appear
  within squares on a grid pattern. In some cases, a
  computer may be used to measure sperm count.
 Semen analysis results
  Normal sperm densities range from 20 million to
  greater than 100 million sperm per milliliter of
  semen. You are considered to have a low sperm
  count if you have fewer than 20 million sperm per
  milliliter. Some men have no sperm in their semen
  at all. This is known as azoospermia
Transudate and Exudate
(Introduction)
 There are various places in the body where fluids
  can accumulate. When fluids accumulate inside a
  cavity they are referred to as effusions. Effusions
  can occur in the pleural, pericardial, and
  peritoneal cavities of the body.
Transudate
 A transudate   is a fluid that accumulates in cavities
  due to a malfunction of the filtering membranes
  of cavity linings.
 The fluid balance between the linings to become
  disrupted, which in turn leads to the buildup of
  fluid on one side of the membrane.
Exudate
 An exudate is a fluid that accumulates inside a
  cavity due to the presence of foreign materials
  such as bacteria, viruses, parasites, fungi, and
  tumor cells.
 An exudate forms as a result of all these cells
  (both leukocytes and foreign material) and their
  metabolites filling the cavity.
How to differentiate transudate
from exudate
 The major test used to differentiate between a
  transudate or an exudate is the concentration of
  total protein in a fluid. Transudates generally have
  total protein concentration less than 3.0 g/dL
  while exudates generally have a total protein
  greater than 3.0 g/dL.
Rivalta Test
 Rivalta test  is used in order to differentiate
  a transudate from an exudate. A test tube is filled
  with distilled water and acetic acid is added. To
  this mixture one drop of the effusion to be tested
  is added. If the drop dissipates, the test is
  negative, indicating a transudate. If the drop
  precipitate, the test is positive, indicating an
  exudate.
Composition, Enzyme Content,
Diagnostic Procedures:
 Lactate dehydrogenase
 Lactate dehydrogenase is an enzyme that is used
  by cells in metabolism and production of energy.
  When there is a large presence of cells and cell
  death such as in infection and inflammation the
  concentration of LDH in the area increases.
 Transudates will have LDH levels lower than 200
  units/L while exudates will have LDH levels higher
  than 200 units/L.
 Glucose    and Amylase
 Decreased values in the concentration of glucose
  in an exudate can occur in bacterial
  infections, malignancies, rheumatoid arthritis, and
  tuberculosis.
 Concentrations of amylase can accumulate in an
  exudate in response to esophageal
  rupture, pancreatitis, and pancreatic cancer. No
  matter what chemistry testing is ordered on a
  fluid it is best to compare it in relation to serum
  levels to help assess whether a fluid is a
  transudate or an exudate
 Leukocytes
 Transudates are generally clear and pale yellow in
  appearance as they are basically filtrates of
  plasma.
 These fluids contain very little cellular material.
  The leukocyte count is usually less than 1.0 X
  109/L and the erythrocyte count is less than 100.0
  X 109/L.
 The leukocytes that are present consist of
  monocytes and lymphocytes.
 Exudates will generally appear cloudy or turbid.
 May appear   yellow, brown, greenish, and even
  bloody.
 In some instances they may even be clotted due
  to the presence of fibrinogen
 The leukocyte count will usually be greater than
  1.0 X 109/L and include
  neutrophils, lymphocytes, monocytes, eosinophils
  , and even basophils.
Synovial Fluid
Composition
 Mucopolysaccaride
 0.9% hyaluronic acid – most important. Functions
  in lubricating the joints
 Albumin
 Globulin
 Glucose
 Lipids
 Nonprotein nitrogenous substances
Enzyme content
 Alkaline phosphatase
 Acid phosphatase
 Lactic dehydrogenase
Function
 Supply nutrients to cartilage
 Act as lubricant to joint surfaces
 Carry away waste products
 String Test-   viscosity and clarity of the fluid can be examined.
   Tests
                                    Viscosity                    Clarity

        Normal Fluid         When dropped from a         Transparent & colorless-
                            syringe, forms a string of         light yellow
                             greater than 10-15cm
     Inflammatory Fluid     Low viscosity & flows like   Cloudy & yellow/green
                                      H20

   Non-inflammatory Fluid                                    Clear & yellow


     Haemorrhagic fluid                                       Cloudy & red/
                                                                red-brown


    *Normal synovial fluid is clear, pale, yellow, viscid, and does not clot
Chemical Tests
 Glucose- typically a bit lower than blood glucose
  levels. May be significantly lower with joint
  inflammation and infection.
 Protein- increased with bacterial infection
 Lactate dehydrogenase- increased level may be
  seen in rheumatoid arthritis, infectious
  arthritis, or gout.
 Uric acid- increased with gout
Microscopic Examination
 Total cell count- number of RBC’s and WBC.
  Increased WBC may be seen in infections such as
  gout & rheumatoid arthritis.
 WBC differential- determines the percentages of
  different types of WBC.
     ↑ neutrophil- seen with bacterial infections
     Greater that 2% eosinophil- suggest Lyme disease
Clinical Disorders
 Increase volume  of the synovial fluid results in a variety of
  pathological process
     Non-inflammatory- Osteoarthritis, neuroarthropathy
     Inflammatory- rheumatoid arthritis, gout
     Septic- Bactericidal or fungal infection
     Haemorrhagic- Haemophilia or trauma
Tears
Enzyme content
 Tears secreted by the lacrimal gland contains the
  enzyme lysozyme which protects the cornea from
  infection by hydrolyzing the mucopeptide of the
  polysaccharide cell walls of many microorganisms.
Function
   Keeps the epithelium moist, thereby protecting the
    outer covering of the eye from damage due to dryness
   Creates a smooth optical surface on the front of the
    cornea
   Acts as the main supplier of oxygen & other nutrients
    to the cornea
   Carries waste products from the cornea
   Improves the quality of retinal image by smoothing out
    irregularities of the cellular surfaces
   Provide enzymes that destroy bacteria that can harm
    the eye
Tests
 Schirmer test
 Meniscometry
Schirmer Test
 Determines whether the eyes
  produces test enough to keep it
  moist
 This test is used when a person
  experiences very dry eyes or
  excessive watering of the eyes
 Performed by placing filter paper
  inside the lower lid of the eye &
  after a few minutes, the paper is
  removed & tested for moisture
  content.
 Flourescein eye drops are also used
  to test if tears can flow through the
  lacrimal ducts into the nose
More than 10 mm of moisture on the
  filter paper in 5 minutes is normal
Meniscometry
 Meniscometry is a
  minimally invasive test,
  which is particularly useful
  in assessing tear volume
  indirectly by measuring tear
  meniscus radius.
 The smaller the radius of
  curvature, the smaller the
  volume of tears present and
  the greater the capillary
  suction of fluid back into
  the menisci from the tear
  film.
Clinical Disorders
 Crocodile tears syndrome
 Keratoconjunctivitis sicca
Crocodile Tears
   An uncommon consequence
    of nerve regeneration
    subsequent to Bell's palsy or
    other damage to the facial
    nerve in which efferent fibers
    from the superior salivary
    nucleus become improperly
    connected to nerve axons
    projecting to the lacrimal
    glands (tear ducts), causing
    one to shed tears (lacrimate)
    during salivation while
    smelling foods or eating.
Keratoconjunctivitis sicca
 Dry eye syndrome
 A relativelycommon
  condition, especially in
  older patients, that is
  characterized by inadequate
  tear film protection of the
  cornea because of either
  inadequate tear production
  or abnormal tear film
  constitution, which results
  in excessively fast
  evaporation or premature
  destruction of the tear film.
Human Breast Milk
 Composition & Function
     Fats
       Needed for the development    of nervous system
       Insulation & component of cell membrane
           Lipid (grams/100ml milk) 4.38
                          FA (8C)              trace
                          PUFA               0.6(14%)



     Carbohydrates
       Provide energy (lactose            is the predominant carb.)

         Carbohydrate (grams/100ml milk)
                       lactose                           7
                       oligosaccharides                 0.5
Human Breast Milk
    Proteins
        Needed for protein synthesis for growth & development
            Composed mostly of whey (60%-80%) & casein
      Protein (grams/100 ml milk)           1.03
                    casein                  0.3
                    a-lactalbumin 0.3       0.3
                    lactoferrin             0.2
                    IgA                     0.1
                    IgG 0.001              0.001
                    lysozyme                0.05
                    serum albumin           0.05
                    ß-lactoglobulin           -
      Contains lactoferrin that has bacteriostatic effect
      Contains antibodies, bifidus factor & digestive enzymes
Human Breast Milk
               Vitamins, minerals and other nutrients
                  Contains a host of vitamins,   minerals and other
                     nutrients that support a host of different biochemical
                     processes essential for life
Ash (%)                          0.20          Riboflavin (mg)          0.036
Calcium (mg)                    25-35          Niacin (mg)              0.177
Iron (mg)                        0.03          Pantothenic acid         0.223
Magnesium (mg)                     3           Vitamin B6 (mg)            10
Phosphorous (mg)                13-16          Folacin (mg)               5
Potassium (mg)                    51           Vitamin B12 (mcg)        0.045
Sodium (mg)                       17           Vitamin A (mg)             58
Zinc (mg)                        0.17          Vitamin D (mg)           0.04
Ascorbic acid (mg)                 5           Vitamin E (mg)           0.34
Thiamine (mg)                     20           Vitamin C (mg)             4
Human Breast Milk
 Control mechanism
     Lactogenesis
       Transforms a mammary       gland from its undifferentiated
        state to fully differentiated state in late pregnancy
       Stage I – occurs in mid-pregnancy
           ↑ in lactose, total protein and immunoglobulins
           ↓ in Na+ and Cl-
       Stage II – onset of milk    secretion
           ↑ in lactose (further increase) and citrate
Human Breast Milk
 Control mechanism
     Lactation
       Abrupt ↓ in progesterone (removal of placenta)
        initiates milk secretion
       Prolactin
           Stimulates and maintains mammary glandular ductal
            growth and milk protein synthesis
       Oxytocin
           Promotes “milk let-down” reflex
Human Breast Milk
Human Breast Milk
 Enzymes
    Lipase
      For fat breakdown

    Lactoperoxidase and lysozymes
      Bactericidal effect

    Other enzymes
      Transport moieties
                        for other substances such as zinc,
       selenium & magnesium
Human Breast Milk
 Diseases associated with breastmilk
     Mastitis
       infection of the tissueof the breast that occurs most
        frequently during the time of breastfeeding
       causes pain, swelling, redness, and increased
        temperature of the breast
       occurs when bacteria, often from the baby's mouth,
        enter a milk duct through a crack in the nipple
       Resolves through antibiotic medication
Human Breast Milk
   Subareolar abscess
     abscess or growth on the  areolar gland, which is located in the
      breast under or below the areola
     cause is blockage of the small glands or ducts under the areola, with
      development of an infection under the skin
     Symptoms may occur as:
         Drainage and possible pus from lump beneath areolar area
         Fever
         General ill-feeling
         Swollen, tender lump beneath areolar area
     Treatment    done with antibiotics
Human Breast Milk
   Duct ectasia syndrome
     occurs when a milk  duct beneath nipple becomes dilated → duct
      walls thicken → duct fills with fluid → milk duct can then become
      blocked or clogged with a thick, sticky substance
     usually improves without treatment
     Antibiotics or surgery only instituted if signs/symptoms persist
         Tenderness in the nipple or surrounding breast tissue
         Redness
         A lump or thickening
         An inverted nipple
Human Breast Milk
   Breast engorgement
     can occur due to :
         sudden increased milk production that is common during the first days
          after the baby is delivered
         when the baby suddenly stops breastfeeding either because it is starting
          to eat solid foods or it is ill and has a poor appetite
     may also be caused when the mother does not nurse or pump the
      breast as much as usual
     alveoli become over-distended which can lead to the rupture of the
      milk-secreting cells
     can lead to cessation of milk production
     Severe engorgement of the breast can lead to breast infection
Human Breast Milk
 Current research for breast milk testing
     breast milk could be used to predict whether she is at risk of
      developing breast cancer, according to scientists
     Cells in the milk can easily be tested to see if they contain certain
      genes linked to the illness
     the DNA of the milk appears altered to those who have shown to
      be (+) to cancer as evidenced by their respective biopsies
Sweat
   Composition
       Highly variable, but Na+ and Cl- are the major electrolytes
       Mineral composition varies depending on the person’s activity
           sodium (0.9 gram/liter)
           potassium (0.2 g/l)
           calcium (0.015 g/l)
           magnesium (0.0013 g/l)
           zinc (0.4 milligrams/liter)
           copper (0.3–0.8 mg/l)
           iron (1 mg/l)
           chromium (0.1 mg/l)
           nickel (0.05 mg/l)
           lead (0.05 mg/l)
Sweat
 Function
     produced by glands in the deeper layer of the skin,
      the dermis
     main function is to control body temperature
     additional function of sweat is to help with gripping,
      by slightly moistening the palms
Sweat
 Enzyme
    Contains cysteine proteinase inhibitors
      inhibits papain which is   known to cleave the Fc portion
       of immunoglobulins
Sweat
 Test
     Sweat Chloride Test
       common and simple    test used to evaluate a patient
        who is suspected of having cystic fibrosis (CF)
       iontophoresis is employed to produce the necessary
        volume of sweat for the test
       normal sweat chloride = 10-35 mEqs/l
       sweat chloride value < 60 mEqs/l is indicative of CF
       Those having intermediate values are advised to have
        the test repeated on a periodic basis
Sweat
   Diseases associated with sweat
       Hyperhydrosis
         abnormal increased sweating
         In most cases, cause is unknown. In some cases, however,
          causes are:
               Obesity
               Hormonal changes associated with menopause (hot flushes)
               Illnesses associated with fever, such as infection or malaria
               An overactive thyroid gland (hyperthyroidism)
               Diabetes
               Certain medications
Sweat
    Idiopathic hyperhydrosis
      most common form of excessive    sweating
      Cause is unknown
      can develop during childhood or later  in life
      can affect any part of the body, but the palms and
       soles or the armpits are the most commonly affected
      occurs even during cool weather, but it is worse during
       warm weather and when a person is under emotional
       stress
Sweat
    Apocrine bromhidrosis
      most prevalent   form of bromhidrosis
      bacterial decomposition of apocrine secretion
       contribute to its pathogenesis
          yields ammonia and short-chain fatty acids having strong
           odors
Sweat
    Eccrine bromhidrosis
      Happens when eccrine   sweat softens keratin
      bacterial degradation of the keratin yields a foul smell
      Can be caused by ingestion of some foods or drugs
       like:
          Garlic
          Onion
          Curry
          Alcohol
          certain drugs (eg: penicillin, bromides)
Mechanisms of Detoxification
Mechanisms of Detoxification
•   Primarily a function of the liver
    •   Has 2 phases
        •   Phase I
            •   Directly neutralizes or converts a substrate into an
                intermediate one.
        •   Phase II
            •   Renders a non-toxic final product.
Phase I
 Involves a group of enzymes – cytochrome P450
  family
     Uses O2 and NADH as a cofactor
     Employs varied reactions depending on the
      substrate to be detoxified
     Free radicals are produced in the process
Phase I
Phase I
 Some substances that can cause   overactivity of
  cytochrome P450 enzymes:
     Caffeine
     Alcohol
     Pesticides
     Sulfonamides
     Barbiturates
Phase I
 Phase I can directly neutralize some chemicals
  like:
     Caffeine
Phase I
 Overactivity of Phase I
     Leads to wide range of chemical tolerances
     Depletion of antioxidants
     Accumulation of intermediate substance
     Predisposition to liver cell damage
 Underactivity of Phase I
     Low tolerance to wide range of chemicals
     Longer detoxification time
Phase I
 Inducers of Phase I
     Foods from brassica family
       Cabbage, broccoli, Brussels sprouts
       Also stimulates Phase II detoxification pathway
       Contains Indole-3-carbinol, a powerful anti-cancer

     Citrus fruits
       Oranges, lemons and tangerines
       Contains limonene that is   a strong inducer of Phase I &
        II
   Nutrients
     Niacin, vitamin   B1, vitamin C
   Herbs
     Caraway and dill seeds
Phase I
   Inhibitors of Phase I
       Drugs
           benzodiazepines; antihistamines; cimetidine;
            ketoconazole
       Foods
         naringenin from grapefruit juice
         curcumin from turmeric
         capsaicin form chili pepper
         eugenol from clove oil
         quercetin from onions
       Aging
Phase II
 Involves conjugation reactions to neutralize toxins
 Essentially, there are 6 pathways
     Glutathione conjugation
     Amino acid conjugation
     Methylation
     Sulfation
     Acetylation
     Glucuronidation
Phase II
Phase II: Glutathione conjugation
 Produces water-soluble mercaptates with the help
  of enzyme GST
Phase II: Amino acid conjugation
 Amino acids take on the action of neutralizing
  toxins
     Glycine is the most commonly used AA in Phase II
      AA detoxification
Phase II: Methylation pathway
 involves conjugating methyl groups to toxins
 methyl groups come from S-adenosyl   methionine (SAM)
     synthesized from methionine
Phase II: Methylation pathway
 Inactivates drugs through methylation like estrogens
Phase II: Sulfation pathway
 conjugation of toxins with sulfur-containing compounds
Phase II: Sulfation pathway
 Main pathway for detoxification od   steroids and thyroid
  hormones
 Primary route for elimination of neurotransmitters
Phase II: Acetylation pathway
 Conjugation of toxins with acetyl-CoA
     Primary elimination of sulfa drugs
 Detoxifies many environmental toxins, including tobacco smoke
  and exhaust fumes
Phase II: Glucuronidation pathway
 Combines glucuronic acid with toxins
 requires the enzyme  UDP-glucuronyl transferase (UDPGT)
 major inactivating pathway for lots of toxins
Phase II: Glucuronidation pathway
 Glucuronidation of   Etoposide
Phase II
 Inducers of Phase II
     Glutathione conjugation:
       Brassica family foods (cabbage, broccoli, Brussels
        sprouts); limonene-containing foods (citrus peel, dill
        weed oil, caraway oil)
     Amino acid conjugation:
       Glycine
     Methylation:
       Lipotropic nutrients
        (choline, methionine, betaine, folic acid, vitamin B12)
Phase II
 Inducers of Phase II
     Sulfation:
       Cysteine, methionine,    taurine
     Acetylation:
       most vegetables     and fruits but especially cruciferous
        vegetables
     Glucuronidation:
       Fish oils,   limonene-containing foods
Phase II
 Inhibitors of Phase II
     Glutathione conjugation:
       Selenium deficiency, vitamin   B2 deficiency, glutathione
        deficiency, zinc deficiency
     Amino acid conjugation:
       Low protein diet

     Methylation:
       Folic acid or vitamin B12 deficiency
Phase II
 Inhibitors of Phase II
     Sulfation:
       Non-steroidal anti-inflammatory  drugs (e.g. aspirin),
        tartrazine (yellow food dye), molybdenum
     Acetylation:
       Vitamin B2, B5, or C deficiency

     Glucuronidation:
       Aspirin, probenecid

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Seminar report body fluids

  • 1. Body Fluids Section A, Group 2 ALFONSO, ALJAMA, ALUZAN AMURAO, ARELLANO, ARROYO
  • 2. Water  Predominant chemical component of living organisms  Universal Solvent  Has a dipolar structure and exceptional capacity for forming hydrogen bonds.
  • 3. pH Scale  The acidity of aqueous solutions is generally reported using the logarithmic pH scale.  Bicarbonate and other buffers normally maintain the pH of extracellular fluid between 7.35 and 7.45
  • 5. Factors for Regulation of Water Balance  Depends upon hypothalamic mechanisms that control thirst.  On Antidiuretic Hormone (ADH)  Evaporative loss  Certain diseases like Diabetes Insipidus
  • 6. Water as an Ideal Biologic Solvent
  • 7. Water Molecules form Dipoles  A water molecule is an irregular, slightly skewed tetrahedron with oxygen at its center.
  • 8. Water Molecules Form Dipoles  Water is a dipole  Water, a strong dipole, has a high dielectric constant.  Its strong dipole and high dielectric constant enable water to dissolve large quantities of charged compounds such as salts.
  • 9. Water Molecules Form Hydrogen Bonds  Hydrogen bonding favors the self-association of water molecules into ordered arrays .
  • 10. Water Molecules Form Hydrogen Bonds  Hydrogen bonding profoundly influences the physical properties of water and accounts for its exceptionally high viscosity, surface tension, and boiling point.  Hydrogen bonding enables water to dissolve many organic biomolecules that contain functional groups which can participate in hydrogen bonding.
  • 11. Interaction with Water Influences the Structure of Biomolecules
  • 12. Covalent & Noncovalent Bonds Stabilize Biologic Molecules:  These forces (covalent and noncovalent bonds), which can be either attractive or repulsive, involve interactions both within the biomolecule and between it and the water that forms the principal component of the surrounding environment.
  • 14. Electrostatic Interactions  Interactions between charged groups shape biomolecular structure.  Electrostatic interactions between oppositely charged groups within or between biomolecules are termed salt bridges.
  • 15. Van der Waals Forces  Van derWaals forces arise from attractions between transient dipoles generated by the rapid movement of electrons on all neutral atoms.
  • 16.
  • 17. Water is an Excellent Nucleophile
  • 18. Water is an excellent nucleophile  Metabolic reactions often involve the attack by lone pairs of electrons on electron-rich molecules termed nucleophiles on electron-poor atoms called electrophiles.  Nucleophiles and electrophiles DO NOT necessarily possess a formal negative or positive charge.
  • 19. Water is an excellent nucleophile  Water, whose two lone pairs of sp3 electrons bear a partial negative charge, is an excellent nucleophile  Nucleophilic attack by water generally results in the cleavage of the amide, glycoside, or ester bonds that hold biopolymers together. This process is termed hydrolysis.
  • 20.  An example of a cleavage of an amide link
  • 21. Water is an excellent nucleophile  Conversely, when monomer units are joined together to form biopolymers such as proteins or glycogen, water is a product.
  • 22. Water Molecules Exhibit a Slight but Important Tendency to Dissociate:  Since water can act both as an acid and as a base, its ionization may be represented as an intermolecular proton transfer that forms a hydronium ion (H3O+) and a hydroxide ion (OH−):
  • 24.  Total body fluid is distributed between two compartments:  Extracellular fluid  interstitial fluid  blood plasma  Intracellular fluid
  • 25. Transcellular Fluid  small compartment containing body fluids formed by the secretion of epithelial cell and is contained within epithelial lined spaces  includes fluid in the synovial, peritoneal, pericardial, and intraocular spaces, as well as the cerebrospinal fluid  specialized type of extracellular fluid  constitute about 1 to 2 liters.
  • 26.
  • 27. In an average 70-kilogram adult human:  Total body water is about 42 liters or 60 percent of the body weight  This percentage can change depending on:  Age  Gender  Degree of obesity.
  • 29. Gender and Body Fat  Women normally have more body fat than men  They contain slightly less water than men in proportion to their body weight
  • 30.
  • 31. Extracellular and Intracellular Fluid  cell membrane is semipermeable, only water and small, noncharged molecules can move freely between interstitial and intracellular compartment. Ion can not cross easily.  All kinds of ionic pump or channel on cell membrane determine the uneven distribution
  • 32.
  • 33. Extracellular and Intracellular Fluid  ICF and ECF are different in ionic composition
  • 34. Intracellular Fluid  About 28 of the 42 liters of fluid in the body are inside the 75 trillion cells  Constitutes about 40 percent of the total body weight  Each cell contains its individual mixture of different constituents, but the concentrations are similar from one cell to another  Composition of cell fluids is remarkably similar even in different animals
  • 35. Extracellular Fluid  All the fluids outside the cells  Account for about 20 percent of the body weight, or about 14 liters in a normal 70-kilogram adult  Two largest compartments: (1) interstitial fluid  more than three fourths of the extracellular fluid, and (2) plasma  almost one fourth of the extracellular fluid, or about 3 liters  *Plasma - non-cellular part of the blood  - exchanges substances with the interstitial fluid (pores of the capillary membranes)  Constantly mixing  plasma and interstitial fluids have about the same composition except for proteins ( [] in the plasma)
  • 36.
  • 37. Hypervolemia  Term used for fluid overload, overhydrated and water excess  It occurs when the body takes in more water than it excretes *  Factors that cause Hypervolemia:  Cardiac failure  Renal failure (Kidney’s Damage)  High sodium intake  Over infusion of intravenous fluids.
  • 38. Observations related to fluid balance
  • 39. Hypervolemia  Infants are especially likely to develop overhydration (first month of life)*  For adults, drinking too much water rarely causes overhydration when the body's systems are working normally  Brain- the organ most vulnerable to the effects of overhydration*
  • 42. Hypervolemia  Treatment  Limit fluidintake  In more serious cases, diuretics may be prescribed to increase urination  Identifying and treating any underlying condition (such as impaired heart or kidney function) is a priority
  • 43. Hypervolemia  NOTE:  The best advice is to drink when you are thirsty and to aim to drink 6-8 glasses, 2-3 litres per day;  *Consider the differences in physical activity, climate and diet  *Less fluid intake for lower intensity exercise in milder conditions and more for superior athletes competing at higher intensities in warmer environments
  • 44. Hypervolemia • The best guidance is for individuals to remain adequately hydrated, but not overhydrated
  • 47.  The average adult body contains 40 liters of H2O. This amount, called total body water, remains fairly constant under normal circumstances.
  • 48. Maintenance of Water Homeostasis  It is a balancing act because the amount of water taken in must equal the amount of water lost.
  • 49. Disturbance of Water Homeostasis  Two categories  Gain or loss of Extracellular fluid volume  Gain or loss of solute  In many instances disturbances of water and homeostasis involve imbalances of both volume and solute.
  • 50. Mechanism of Fluid Balance  Antidiuretic Hormone  Thirst mechanism  Aldosterone  Sympathetic Nervous System
  • 52. Thirst mechanism  The prime regulator of water intake and involves hormonal and neural input as well as voluntary behaviors.
  • 53.
  • 54.
  • 55.
  • 57. Electrolytes  Cations  Anions  Electrolytes are not evenlydistributed within the body, and their uneven distribution allows many important metabolic reactions to occur
  • 58. Purpose of Electrolytes  Help control water balance and fluid distribution in the body  Create an electrical gradient across cell membranes that is necessary for muscle contraction and nerve transmission  Regulate the acidity (pH) of the blood  Help regulate the level of oxygen in the blood  Are involved in moving nutrients into cells and waste products out of cells
  • 59. Specific Function  Sodium- affects how much urine the kidney produces and is involved in the transmission of nerve impulses and muscle contraction  Potassium- regulate fluid balance in cells, the transmission of nerve impulses, and in muscle contractions  Calcium-build and maintain bones. It also plays a role in nerve impulse transmission and muscle contraction.
  • 60. Specific Function  Magnesium- involved in protein synthesis and cellular metabolism  Chloride- involved in regulating blood pressure  Phosphate- helps control the acidity level (pH) of the blood; also causes calcium to be deposited in bones
  • 64. Saliva (Composition)  Inorganic composition  dependent on stimulus and rate of salivary flow  Major components are Na+, K+, HCO3-, Ca++, Mg++, and Cl-.  [] of ions varies with the rate of secretion  which is stimulated during the postprandial period.  Organic constituents  synthesized, stored, and secreted by the acinar cells  Major products are amylase, lipase, glycoprotein (mucin, which forms mucus when hydrated), and lysozyme (attacks bacterial cell walls to limit colonization of bacteria in the mouth)
  • 65. Saliva (Enzyme Content)  2 major types of protein secretion:  Serous secretion  contains ptyalin, an amylase enzyme for digesting starches and cleansing agent for the oral cavity  *Saliva has a pH between 6.0 and 7.0 (favorable range for the digestive action of ptyalin)  Mucus secretion  contains mucin for lubricating and for surface protective purposes
  • 66. Saliva (Enzyme Content)  Parotid glands - serous type of secretion  Submandibular and Sublingual glands - both serous secretion and mucus  Buccal glands - secrete only mucus  *Aside from amylase, saliva has presence of other enzymes such as maltase, catalase, lipase, urease, and protease.
  • 68. Saliva (Control Mechanism)  Salivary glands  controlled mainly by parasympathetic nervous signals, from the superior and inferior salivatory nuclei in the brain stem  Salivatory nuclei  excited by both taste and tactile stimuli from the tongue, mouth and pharynx  *  salivation  taste stimuli, especially sour taste (caused by acids), tactile stimuli, such as the presence of smooth objects in the mouth
  • 69. Saliva (Control Mechanism)  Salivation can be stimulated or inhibited by nervous signals arriving in the salivatory nuclei from CNS  Appetite area of the brain  located in proximity to the parasympathetic centers of the anterior hypothalamus, functions to in response to signals from the taste and smell areas of the cerebral cortex or amygdala.
  • 70. Saliva (Control Mechanism)  Saliva  helps remove the irritating factor in the GIT (diluting or neutralizing the irritant substances)  Sympathetic nerves  from Superior cervical ganglia  Salivary glands (slight increase in salivation)  2 factor - blood supply to the glands (nutrition)  Parasympathetic nerve signals  copious salivation  moderately dilate the blood vessels  increased salivatory gland nutrition
  • 71. Saliva (Functions)  Digestive function (enzymes)  Moistens and lubricates food  swallowed easily  Holds the taste-producing substances  brings in contact with the taste buds  Dilutes salts, acids  protecting the mucosa (teeth)
  • 72. Saliva (Function on Oral Hygiene)  Under basal awake conditions  about 0.5 ml/ min of saliva (mucous type)  *During sleep, secretion becomes very little.  Saliva helps prevent deteriorative processes in several ways: 1. Wash away pathogenic bacteria and food particles that provide their metabolic support 2. Contains thiocyanate ions and lysozyme 3. Contains protein antibodies that can destroy oral bacteria, including some that cause dental caries  *In the absence of salivation, oral tissues  often become ulcerated and infected  caries of the teeth can become rampant.
  • 73. Saliva (Tests)  Saliva is easy to access and collection is non-invasive  Used to identify individuals with disease (presence of biomarkers) and to monitor progress under treatment  Viral infections such as human immunodeficiency virus (HIV), herpes, hepatitis C, and Epstein-Barr virus infection  polymerase chain reaction (PCR) techniques  Bacterial infections, such as Helicobacter pylori, can likewise be detected in saliva  Monitoring drugs levels
  • 74. Saliva (Clinical Disorders)  *Abnormal production of the salivary glands can cause serious complications & adverse effects to salivary functions.  Xerostomia (dry mouth) is caused by impaired salivary secretion  Congenital or develop as part of an autoimmune process  Decrease in secretion  reduces pH in the oral cavity  tooth decay and is associated with esophageal erosions  difficulty swallowing.
  • 75. Gastric Juice  Stomach mucosa has two important types of tubular glands: (1) oxyntic glands (gastric glands) and (2) pyloric glands.  Oxyntic (acid-forming) glands - secrete HCL, pepsinogen, intrinsic factor, and mucus  3 types of cells: (1) mucous neck cells (mucus); (2) peptic or chief cells (pepsinogen); and (3) parietal or oxyntic cells (hydrochloric acid and intrinsic factor)  Pyloric glands - secrete mainly mucus (protection of the pyloric mucosa from the stomach acid) and hormone gastrin.
  • 76. Composition: Inorganic Constituents   Secretory rate  Higher the concentration of ions  [K+] is always higher in gastric juice than in plasma (prolonged vomiting may lead to hypokalemia).  At high rates of secretion, gastric juice resembles an isotonic solution of HCl  Gastric HCl converts pepsinogens to active pepsins and provides the acid pH at which pepsins are active
  • 77. Composition: Inorganic Constituents  Rate of gastric H+ secretion varies considerably among individuals  Basal (unstimulated) rates of gastric H+ production  1 to 5 mEq/hr  During maximal stimulation, HCl production  from 6 to 40 mEq/hr  Total number of parietal cells in the stomach  partly responsible for the wide range in basal and stimulated rates of HCl secretion.
  • 78. Gastric Juice Composition: Organic Constituents  Pepsin  proteases secreted by the chief cells, active at pH 3 & below Pepsinogen  the inactive proenzyme of pepsin  Pepsinogens - contained in membrane-bound zymogen granules in the chief cells - converted to active pepsins by the cleavage of acid- labile linkages (the lower the pH, the more rapid the conversion)
  • 79. Gastric Juice Enzyme Content Pepsin  Pepsinogen - no digestive activity, activated to pepsin when comes in contact with HCL  Pepsin - proteolytic enzyme (optimum pH 1.8 to 3.5), above pH 5  almost no proteolytic activity (inactivated)  Major products of pepsin action  large peptide fragments and some free amino acids  Gastric protein digestion  important in peptides and amino acids generation  stimulants for cholecystokinin release in the duodenum * Gastric peptides are therefore instrumental in the initiation of the pancreatic phase of protein digestion
  • 80. Gastric Juice Enzyme Content Gastric Lipase  Initiating the digestion of lipids in the stomach.  Converts triacylglycerols into fatty acids and diacylglycerols  Initial hydrolysis  important since some of the water-immiscible triacylglycerols are converted to products with both polar and non- polar groups (stable interface with the aqueous environment)
  • 81. Gastric Juice Control Mechanism: SECRETION Gastric secretion occur in three phases: (1) cephalic phase, (2) gastric phase, and (3) intestinal phase
  • 82. Gastric Juice Control Mechanism Cephalic phase  Occurs even before food enters the stomach, especially while it is being eaten  Results from the sight, smell, thought, or taste of food, and the greater the appetite, the more intense is the stimulation  Neurogenic signals originate in the cerebral cortex and appetite centers of the amygdala and hypothalamus  transmitted through the dorsal motor nuclei of the vagus  vagus nerves to the stomach
  • 83. Gastric Juice Control Mechanism Gastric phase  Once food enters the stomach  excites the long vagovagal reflexes from the stomach to the brain and back to the stomach  local enteric reflexes  gastrin mechanism  cause secretion of gastric juice during several hours while food remains in the stomach  Accounts for about 70 per cent of the total gastric secretion associated with eating a meal (1500 ml).
  • 84. Gastric Juice Control Mechanism Intestinal phase Presence of food in the upper portion of the small intestine (duodenum)  cause stomach secretion of small amounts of gastric juice (partly because of small amounts of gastrin released by the duodenal mucosa)
  • 85. Gastric Juice Control Mechanism: INHIBITION  Affected by other post-stomach intestinal factors  Presence of food in the small intestine  reverse enterogastric reflex  transmitted through the myenteric nervous system, extrinsic sympathetic and vagus nerves  inhibits stomach secretion  Can be initiated: distending the small bowel, presence of acid (upper intestine), presence of protein breakdown products, or by irritation of the mucosa  This is part of the complex mechanism for slowing stomach emptying when the intestines are already filled.
  • 86. Gastric Juice Control Mechanism: INHIBITION  Release of several intestinal hormones  Secretin - important for control of pancreatic secretion but opposes stomach secretion  Gastric inhibitory peptide, vasoactive intestinal polypeptide, and somatostatin - slight to moderate effects in inhibiting gastric secretion  Functional purpose of inhibitory gastric secretion: to slow passage of chyme from the stomach when the small intestine is already filled or already overactive  Enterogastric inhibitory reflexes plus inhibitory hormones also reduce stomach motility at the same time that they reduce gastric secretion
  • 87. Gastric Juice Functions  Gastric juice is characterized by the presence of hydrochloric acid and therefore a low pH less than 2 as well as the presence of proteases of the pepsin family  Acid serves to kill off microorganisms and also to denature proteins *Denaturation makes proteins more susceptible to hydrolysis by proteases  Serves in the initial hydrolysis of lipids with the help of gastric lipase enzyme
  • 88. Gastric Juice Tests  Qualitative tests include those for butyric acid, lactic acid, occult blood, bile and trypsin.  Presence of the first two acids  yeast or other microorganisms in the gastric secretions  lack of hydrochloric acid  If blood is present  ulcers, hemorrhages and other pathologic states  Either bile or trypsin  evidence of regurgitation of intestinal contents  Quantitative procedures  total acidity contributed by HCL, organic acids and acid salts, neutralized or buffered by various constituents of the gastric juice and food
  • 89. Gastric Juice Clinical Disorders  Achlorhydia - absence of hydrochloric acid (pernicious anemia, gastric carcinoma)  Hypoacidity - if HCL is not entirely absent but below normal (pregnancy, gastric carcinoma, gastritis and constipation, secondary anemia, and chronic debilitative diseases)  Hyperacidity - acidity is elevated (duodenal ulcer and gallbladder disease) *It should be emphasized that the acidity cannot exceed a certain value (pH 0.87) since the parietal cells secrete a fluid of constant composition
  • 91. Pancreatic Juice  The pancreas, parallel to and beneath the stomach, is a large compound gland similar to the internal structure of salivary glands  Exocrine secretion: combined product of enzymes and sodium bicarbonate secretions  flows through a long pancreatic duct  joins the hepatic duct  empties into the duodenum through the papilla of Vater, surrounded by the sphincter of Oddi.  The pancreas also secretes insulin (not secreted by the same pancreatic tissue secreting pancreatic juice)  Insulin is secreted directly into the blood—not into the intestine—by the islets of Langerhans that occur in islet patches throughout the pancreas
  • 92. Pancreatic Juice Composition  Alkaline in nature with a pH of about 8.  Large volumes of sodium bicarbonate solution are secreted by the small ductules and larger ducts leading from the acini  Bicarbonate ions play an important role in neutralizing the acidity of the chyme emptied from the stomach into the duodenum.  The pancreatic digestive enzymes are secreted by pancreatic acini
  • 93. Pancreatic Juice Enzyme Content  Pancreatic secretion contains multiple enzymes for digesting all of the three major types of food: proteins, carbohydrates, and fats Proteins:  Trypsin and chymotrypsin  split whole and partially digested proteins into peptides of various sizes (do not cause release of individual amino acids)  Carboxypolypeptidase  split some peptides into individual amino acids  completing digestion of some proteins all the way to the amino acid state
  • 94. Pancreatic Juice Enzyme Content  Proteolytic digestive enzymes - inactive forms first: trypsinogen, chymotrypsinogen, and procarboxypolypeptidase  Activated after secreted into the intestinal tract  Trypsinogen  activated by an enzyme called enterokinase (secreted by the intestinal mucosa when chyme comes in contact with it) or by previously activated trypsin  Chymotrypsinogen and Procarboxypolypeptidase  activated by trypsin to form chymotrypsin and carboxypolypeptidase
  • 95. Pancreatic Juice Enzyme Content Carbohydrates:  Pancreatic amylase  which hydrolyzes starches, glycogen, and most other carbohydrates (except cellulose)  form mostly disaccharides and a few trisaccharides Fat:  Pancreatic lipase  hydrolyzing neutral fat into fatty acids and monoglycerides  Cholesterol esterase  hydrolysis of cholesterol esters  Phospholipase  splits fatty acids from phospholipids
  • 96. Pancreatic Juice Control Mechanism 3 Basic stimuli for pancreatic secretion  Acetylcholine  released from the parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system  Cholecystokinin  secreted by the duodenal and upper jejunal mucosa when food enters the small intestine  Secretin  secreted by the duodenal and jejunal mucosa when highly acid food enters the small intestine
  • 97. Pancreatic Juice Control Mechanism  Acetylcholine and cholecystokinin  stimulate the acinar cells of the pancreas  production of large quantities of pancreatic digestive enzymes (relatively small quantities of water and electrolytes) *Without water, most of the enzymes remain temporarily stored in the acini and ducts until more fluid secretion comes along to wash them into the duodenum  Secretin  stimulates secretion of large quantities of water solution of sodium bicarbonate by the pancreatic ductal epithelium
  • 99. Pancreatic Juice Control Mechanism Pancreatic secretion occurs in three phases: (1) cephalic phase, (2) gastric phase and (3)intestinal phase Cephalic phase  same nervous signals from the brain that cause secretion in the stomach  cause acetylcholine release by the vagal nerve endings in the pancreas  causes moderate amounts of enzymes to be secreted into the pancreatic acini *Accounting for about 20 per cent of the total secretion of pancreatic enzymes after a meal
  • 100. Pancreatic Juice Functions  Secretions from pancreas  quantitatively the largest contributors to enzymatic digestion of food  Provides additional important secretory products that are vital for normal digestive function including  Water and bicarbonate ions  neutralizing gastric acid so that the small intestinal lumen has a pH approaching 7.0.  reduces injury to small intestinal mucosa by such acid acting in combination with pepsin *Pancreatic enzymes are inactivated by high levels of acidity
  • 101. Pancreatic Juice Tests  The fact that secretin stimulates the flow of pancreatic juice has been made use as a test of external pancreatic functions  Double-lumen tube  passed (longer end reaches the third portion of the duodenum and the shorter end remains in the stomach)  continuous aspiration (-20 to 30 mmHg) prevents the overflow of gastric juice into the duodenum and sucks out both gastric juice and duodenal contents into separate containers  secretin is injected intravenously after a basal flow has been obtained  volume of flow and bicarbonate concentration is measured
  • 102. Pancreatic Juice Tests  Outpouring of pancreatic juice  Under normal conditions, duodenal fluid  lose its biliary color  If the bile color remains  a non-functioning gallbladder is indicated  The total volume varies normally from 135 to 250 ml in 1 hour, and the bicarbonate, from 90 to 130 mEq *In pancreatitis with extensive destruction of parenchymal structures, there is usually a diminution in the volume of pancreatic juice and bicarbonate output
  • 103. Pancreatic Juice Clinical DIsorders  Damaged pancreas/ ducts blocked  large quantities of pancreatic secretion become pooled in the damaged areas  Pancreatitis  enzymes secreted by pancreatic acinar cells become proteolytically activated before reaching appropriate site of action (small intestinal lumen)  Pancreatic juice contains trypsin inhibitors  reduce the risk of premature activation  Trypsin can itself be degraded by other trypsin molecules *Specific mutation in trypsin  renders it resistant to degradation by other trypsin molecules.
  • 104. Pancreatic Juice Clinical DIsorders  Pancreas reacts very sensitively to an impairment of the protein metabolism  Decreased supply of proteins leads  impairment of the endogenous stimulation of pancreas  atrophy of acinous cells and fibrosis of pancreas (e.g. long-term fasting) Decreased contents of pancreatic enzymes  Decreased secretion of their proenzymes, insufficient intraluminal activation or inactivation of enzymes *Celiac sprue  secretions of lipase and trypsinogen are decreased  trypsin deficiency  deficiency of chymotrypsin and other enzymes which are activated from proenzymes by trypsin
  • 105. BILE  An alkaline, brownish- yellow or greenish-yellow fluid that is secreted by the liver, stored in the gallbladder, and discharged into the duodenum and aids in the emulsification, digestion, an d absorption of fats.
  • 106. Bile Composition  Water (85%),  bile salts (10%),(Cholic, chenodeoxycholic, deoxycholi c, and lithocholic acid)  mucus • pigments (3%), bile pigments e.g bilirubin glucuronide • fats (1%), such as Phospholipids (lecithin) , cholesterol • 0.7% inorganic salts
  • 107. Bile Composition  In concentrating process in gallbladder, water and large portions of electrolytes are reabsorbed by gallbladder mucosa  Bile salts and lipid substances cholesterol and lecithin, are not reabsorbed  The concentrated bile is composed of bile salts, cholesterol, lecithin, and bilirubin.
  • 108. Bile Pigments  Bilirubin and Biliverdin* Urobilin Urobilinogen Bilirubin Biliverdin (Brown) (colorless) (red) (green)
  • 109. Bile Secretion Release of hormone Bile is subsequently secretin and CCK stored & concentrated in (chocystokinin) from the the gallbladder between duodenum increase bile meals secretion Bile is normally stored in gallbladder until needed in duodenum*
  • 110. Bile Secretion  After meal, bile enters the duodenum as a result of combined effects of :  Gall bladder emptying  Increased bile secretion by liver  The amount of bile secreted per day ranges from 250 ml to 1 litre
  • 111. Emptying of Gallbladder Gallbladder begins to empty, when food (fatty Gallbladder emptying is foods) reach the rhythmical contractions of duodenum about 30 the gallbladder* minutes after a meal* Effective emptying requires simultaneous relaxation of sphincter of oddi*
  • 112.
  • 113. Bladder bile vs. Liver bile bile (%) Constituent Bladder bile (%) Liver Water 82.3-89.8 96.5-97.5 Solids 10.2-17.7 2.5-3.5 Bile Salts 5.7-10.8 0.9-1.8 Mucus and Pigments 1.5-3.0 0.4-0.5 Cholesterol and other 0.5-4.7 0.2-0.4 lipids Inorganic Salts 0.6-1.1 0.7-0.8
  • 114. ENTEROHEPATIC CIRCULATION  About 95% of the salts secreted in bile are reabsorbed actively in the terminal ileum and re-used. Blood from the ileum flows directly to the hepatic portal vein and returns to the liver where the hepatocytes reabsorb the salts and return them to the bile ducts to be re- used, sometimes two to three times with each meal.
  • 115. Function of Bile Juice*  Bile acts as a surfactant , helping to emulsify the fats in the food.  Bile salt anions have a hydrophilic side and a hydrophobic side, and therefore tend to aggregate around droplets of fat ( triglycerides and phosphiolipids ) to form micelles.  The hydrophilic sides are positively charged due to the lecithin and other phospholipids that compose bile, and this charge prevents fat droplets coated with bile from re-aggregating into larger fat particles.  Fat in micelles* form provide a large surface area for the action of the enzyme pancreatic lipase in the digestion of lipids.
  • 117. Function of Bile Juice  The alkaline bile has the function of neutralizing any excess stomach acid before it enters the ileum.  Bile salts also act as bactericides, destroying many of the microbes that may be present in the food.
  • 118. Preventing Metabolic Deficit  Without the presence of bile salts in the intestinal tract, up to 40 percent of the ingested fats are lost into the feces, and the person often develops a metabolic deficit because of this nutrient loss.
  • 119. Abnormalities associated with bile  Gall stone- majority of gall stones are made up of cholesterol , (cholesterol tends to accrete into lumps in the gallbladder)  Causes of gall stones;  - Too much absorbtion of water from the bile .  - Too much cholesterol in bile.  - Inflammation of the epithelium.
  • 120. Small intestine juice  small intestine is where most chemical digestionand fluid absorption takes place  Water and lipids are absorbed by passive diffusion throughout the small intestine.  Sodium Bicarbonate is absorbed by active transport and glucose and amino acid co-transport  Fructose is absorbed by facilitated diffusion
  • 121. Intestinal Juice  Intestinal juice is not as definite an entity as pancreatic juice or gastric juice because it varies at different levels of intestinal tract*  Succus entericus is influenced by the hormone secretin  Enterocrinin* stimulates mucosal glands
  • 122. Intestinal Juice* leukocytes Epithelial cells Mucus Organic material 1.5% Solid 8.3 pH* eg. mucoproteins components* and enzyme*
  • 123. Feces Formation and Composition Feces is the waste material passed out from the bowels through the anus.  It is usually solid to semi- solid in consistency but can be hard in constipation or watery with diarrhea
  • 124. Feces Formation  Large amounts of water and electrolytes are absorbed in the first half of colon.*  Water absorption transforms the fluid chyme into a mush-like consistency by the time it passes through the transverse colon.  It solidifies further along its passage down the descending colon.
  • 125. Composition of Feces  About 75% of fecal weight is made up of water.  The other 25% is composed of solid matter which contains :  Undigested fiber and solidified components of digestive juices (30%)  Bacteria (30%)  Fat (10% to 20%)  Inorganic matter (10% to 20%)  Protein (2% to 3%)
  • 126. Water and Electrolytes in the Colon  Electrolytes(bicarbonate) are secreted by the wall of the large intestine into the lumen to neutralize any acidic byproducts of bacterial metabolism.  Sodium and chloride are absorbed by the intestinal wall which creates a concentration gradient to facilitate water absorption.
  • 127. Feces  *Any extra fluid remain in the colon give a liquid consistency to the feces (loose stool).  It also increases defecation frequency by triggering the local defecation reflex.
  • 128. Feces  The Bristol Stool Chartor Bristol Stool Scale is a medical aid designed to classify the form of human feces into seven categories The form of the stool depends on the time it spends in the colon.
  • 129. Color of feces  Feces usually has a brown color, ranging from a tan hue to a darker-brown color.  Bilirubin is passed out in the bile and the action of bacteria and air in the gut breaks it down into stercobilin and urobilin, which gives stool its typical color.
  • 130. Smell of Feces  Odor - H2S (rotten egg smell) - mercaptans (sewer gas)
  • 131.
  • 132. Characteristics Characteristics of urine under physiological conditions Characteristic Normal Quantity or Quality Volume 115 to 180 L /day (women) 130 t0 200 L / day (men) Color Amber Odor Not unpleasant (aromatic) Turbidity Clear and transparent pH 4.6 to 8.0
  • 133.  Color  Odor  Amber  Does not have unpleasant  Pigment: urochrome smell (aromatic)  Other pigments:  Other odors arise from food uroerythrin, uroporphyrins,  Mercaptan-like odor after riboflavin eating asparagus  Oil of wintergreen (has methyl salicylate)  strong odor of evergreens
  • 134.  Turbidity  pH  Urine is clear and  Varies from 4.6 to 8.0 transparent  Protein diet gives rise to  After standing for a long acidic pH  oxidation of sulfur in sulfur containing time  flocculent material amino acids into sulfuric (mucoprotein + acid nucleoprotein + epithelial  Vegetable and fruit diet cells) separates gives rise to alkaline urine  Urine samples taken right after eating meals are alklalinesecretion of H+ in the gastric juice
  • 135. Ions in the urine  Anions  Cations  The major anion is chloride  Sodium and potassium are  The amount is equal to the the major cations amount that was ingested  Total excretion of Na+ varies  In salt-poor diets, Cl- may be between 2.0 and 4.0 g/day absent  K+ 1.5 to 2.0 g/day.
  • 136. Nitrogenous organic compounds Component Amount  Urea α the total nitrogen Urea 12 to 36 g per intake day (70-g  Uric acid – end product of adult) purine metabolism; α purine Uric acid 0.7 g of uric intake acid per day  Creatinine α muscle mass Creatinine 18 to 32 and  Creatine predominant in (coefficient) 10 to 25 in children and pregnant women women Hippuric acid 0.7 g per day  Hippuric acid - formed in the liver Indican 5 to 25 mg per  Indican – potassium salt day
  • 137. Composition Normal concentration of organic compounds, anions, and cations in urine Component Concentration in Concentration in [U]/[P]* urine (mg percent) blood (mg percent) Urea 2000 30 67 Uric acid 60 2 30 Creatinine 75 2 37 Indican 1 0.05 20 Phosphate 150 3 50 Sulfate 150 3 50 Potassium 150 20 7.5 Chloride 500 350 1.4 Sodium 350 335 1 Calcium 15 10 1.5 * Concentration in urine / concentration in blood plasma
  • 138. Glycosuria  The normal glucose range is 10 to 20 mg per 100 mL or urine  High amounts of sugars lead to glycosuria  Glucosuria  Pentosuria  Lactosuria  Galactosuria  Fructosuria
  • 139.  Pentosuria  Tests for pentosuria  Occurs after eating unusual  Benzidine + acetic acid + amounts of fruits and fruit urine  mixture is heated juices then cooled  rose-pink  Idiopathic pentosuria – color (+ for pentose) occurs in the absence of L-  (+) Benedict’s reagent xylulose dehydrogenase (a  (-) baker’s yeast genetic disease) fermentation  Xylulose is excreted in the urine
  • 140.  Lactosuria  Tests for lactosuria  Moderate amounts of  (+) baker’s yeast lactose secretion is found in fermentation lactating women  (+) mucic acid test  Does not occur in pregnancy  (-) Barfoed’s test  Yields lactosazone
  • 141.  Fructosuria  Tests for fructosuria  Occurs in association with  (+) Benedict’s reagent diabetes mellitus  (+) baker’s yeast  The site of difficulty is the fermentation liver (it’s where fructose is  Yields glucosazone and stored as glycogen phenylhydrazine  There is a deficiency in the enzyme fructokinase
  • 142.  Galactosuria  Tests for galactosuria  A consequence of  reduction of alkaline copper galactosemia solutions  Galactose is not detectable  slight fermentation by in the urine prior to the baker’s yeast introduction of milk in the  (+) Barfoed’s test diet  (+) mucic acid test.
  • 143.  Proteinuria  Tests for Proteinuria  presence of proteins, most  Nitric acid ring test especially albumin, in the  Sulfosalicylic acid test – urine. degree of turbidity (+)  Plasma proteins may pass  Heat and acetic acid test – damaged renal epithelium ring of white turbidity (+)
  • 144. Lipuria  presence of large amounts of fat in the urine  Urine is opalescent, turbid, or milky when voided  The high blood fat (lipemia) that sometimes occurs in diabetes mellitus and lipoid nephrosis may lead to lipuria.  Also in patients with fractures of the long bones with injury to the bone marrow
  • 146.  The lymphatic system maintains volume and pressure of the extracellular fluid  returns excess water and dissolved substances from the interstitial fluid to the circulation  Lymph is the fluid that is present in the lymphatic capillaries that drain the interstitial spaces.
  • 147. Mechanism of lymph flow  Travels down the pressure gradient.  Muscular and respiratory pumps push the lymph forward via the action of semilunar valves.  blood capillaries  interstitial fluid  lymph capillaries  lymphatic veins  lymph nodes  lymph ducts and finally  brachiocephalic veins and vena cavae.
  • 148. Composition  Lymph has a similar composition to blood plasma.  The only difference is that it contains lower percentage of protein than blood plasma.  Lymph albumin:globulin ratio > plasma albumin:globulin ratio  Albumin is smaller than globulin  it diffuses from plasma to lymph more readily than the latter.  Fibrinogen, prothrombin, and leukocytes are present in lymph, too.
  • 149.  The composition of lymph varies with the state of digestion.  After a meal, the fat content rises since more than half the fat absorbed goes by this route. The lymph becomes milky if the food contains much fat.  Lymph has the same composition as the ISF  Asit flows through the lymph nodes it comes in contact with blood, and tends to accumulate more cells (particularly, lymphocytes) and proteins.
  • 150.  Anedema that is caused by the blockage of lymph return
  • 152. CSF functions in  protecting the brain from sudden changes in pressures.  Maintaining a stable environment  removing waste products of the cerebral hemisphere.
  • 153. Production of CSF choroid plexus P P subarachnoid in the cisternae space ventricles arachnoid villi venous blood
  • 154. Characteristics of CSF under physiological conditions Characteristic Normal Quantity or Quality Volume 20 mL per day Color Colorless Specific gravity 1.004 to 1.008 Turbidity Clear pH 7.35 to 7.40
  • 155. Component Concentration or ratio in CSF Glucose <4.5 mmol/L Lactate <2.1 mmol/L Proteins 0.15 to 0.45 g/L IgG (blood to CSF 500:1 ratio) IgG index 0.66
  • 156. CSF Pathology  Spinal cord disorders (compressive syndrome)  Hemorrhage  Infections (meningitis, encephalitis, myelitis)  Inflammatory autoimmune diseases (multiple sclerosis, Guillain-Barré syndrome)  Systemic autoimmune diseases (vasculitis, systemic lupus erythematosus)  Malignancy  Degenerative processes (Alzheimer’s syndrome, amyotrophic lateral sclerosis, Parkinson’s disease)  Demyelinating disease
  • 157.  CSF is collected using lumbar puncture. The appearance and pressure of CSF are evaluated to know what kind of pathology is present in an individual.
  • 158. Lange’s colloidal gold test  Done by mixing decreasing dilutions of CSF with colloidal gold solution  Normal CSF causes no change in the appearance of the orange-red colored • Paretic curve solution • Fluids with large globulin  Fluids with pathologic content conditions produce color • Such curves are contained in change depending on the casese with general paralysis condition and dilutiona • Multiple sclerosis, lead poisoning with brain involvement
  • 159.  Luetic curve • Meningitic curve  Fluids with limited globulin • Large amounts of globulin and and moderate albumin content globulin  Certain forms of cerebro-spinal • All meningitic conditions show syphilis this kind of curve  Also in brain tumor, poliomyelitis, and cerebral arteriosclerosis
  • 160. Sperm & Semen (Contents)  Fructose – this serves as the primary nutrient source of the sperm cells.  Citric Acid – no definite function for the sperm. But is a basis for diagnosing acute and chronic prostatitis  Fibrinogen – forms a clot when the semen is introduced to the reproductive tract, forms a clot for 15 mins then disintegrates to promote sperm motility.
  • 161.  Prostaglandins – makes the female reproductive tract more receptive to sperm movement and possibly causes backward, reverse peristaltic movement to propel the sperm towards the ovaries. (A sperm cell can reach the upper ends of the fallopian tube within 5 minutes)  Profibrinolysin – is changed to fibrinolysin to dissolve the clot formed by the fibrinogen  Calcium ion – enters the sperm when it is within the female reproductive tract thus giving the sperm a whiplash motion.
  • 162. Contained in the acrosome  Hyaluronidase – depolymerizes the hyaluronic acid polymers in the intercellular cement that holds the ovarian granulosa cells together.  Proteolytic enzymes – digest proteins in the structural elements of tissue cells that still adhere to the ovum
  • 163.
  • 164.  The Prostate glands secretes a thin milky fluid that contains calcium, citrate ion, phosphate ion, a clotting enzyme and profibrinolysin.  Alkalinic pH is to combat the Acidic pH of the vagina (pH of 3.5 to 4.0). The sperm becomes motile when the pH rises to about 6.0 to 6.5.
  • 165. Control Mechanism  Spermatogenesis  Testosterone, secreted by the Leydig cells, essential for growth and division of the testicular germinal cells, first stage in forming sperm cells.  Luteinizing hormone, stimulate the Leydig cells to release testosterone
  • 166. Control Mechanism  Follicle-stimulating hormone, stimulates the Sertoli cells; without this stimulation, the conversion of the spermatids to sperm will not occur.  Estrogens, essential for spermiogenesis  Growth hormone, promotes early division of the spermatogonia
  • 167. Diagnostic Procedures  Semen Allergy Test - Women with seminal plasma protein allergy (SPPA) have an immunologic response to human semen. The immunological mechanism of semen allergy is a type I hypersensitivity reactions.
  • 168.  Semen Analysis - A low sperm count is diagnosed as part of a semen analysis test. Sperm count is generally determined by examining semen under a microscope to see how many sperm appear within squares on a grid pattern. In some cases, a computer may be used to measure sperm count.
  • 169.
  • 170.  Semen analysis results Normal sperm densities range from 20 million to greater than 100 million sperm per milliliter of semen. You are considered to have a low sperm count if you have fewer than 20 million sperm per milliliter. Some men have no sperm in their semen at all. This is known as azoospermia
  • 171. Transudate and Exudate (Introduction)  There are various places in the body where fluids can accumulate. When fluids accumulate inside a cavity they are referred to as effusions. Effusions can occur in the pleural, pericardial, and peritoneal cavities of the body.
  • 172. Transudate  A transudate is a fluid that accumulates in cavities due to a malfunction of the filtering membranes of cavity linings.  The fluid balance between the linings to become disrupted, which in turn leads to the buildup of fluid on one side of the membrane.
  • 173. Exudate  An exudate is a fluid that accumulates inside a cavity due to the presence of foreign materials such as bacteria, viruses, parasites, fungi, and tumor cells.
  • 174.  An exudate forms as a result of all these cells (both leukocytes and foreign material) and their metabolites filling the cavity.
  • 175. How to differentiate transudate from exudate  The major test used to differentiate between a transudate or an exudate is the concentration of total protein in a fluid. Transudates generally have total protein concentration less than 3.0 g/dL while exudates generally have a total protein greater than 3.0 g/dL.
  • 176. Rivalta Test  Rivalta test is used in order to differentiate a transudate from an exudate. A test tube is filled with distilled water and acetic acid is added. To this mixture one drop of the effusion to be tested is added. If the drop dissipates, the test is negative, indicating a transudate. If the drop precipitate, the test is positive, indicating an exudate.
  • 177.
  • 178. Composition, Enzyme Content, Diagnostic Procedures:  Lactate dehydrogenase  Lactate dehydrogenase is an enzyme that is used by cells in metabolism and production of energy. When there is a large presence of cells and cell death such as in infection and inflammation the concentration of LDH in the area increases.  Transudates will have LDH levels lower than 200 units/L while exudates will have LDH levels higher than 200 units/L.
  • 179.  Glucose and Amylase  Decreased values in the concentration of glucose in an exudate can occur in bacterial infections, malignancies, rheumatoid arthritis, and tuberculosis.  Concentrations of amylase can accumulate in an exudate in response to esophageal rupture, pancreatitis, and pancreatic cancer. No matter what chemistry testing is ordered on a fluid it is best to compare it in relation to serum levels to help assess whether a fluid is a transudate or an exudate
  • 180.  Leukocytes  Transudates are generally clear and pale yellow in appearance as they are basically filtrates of plasma.  These fluids contain very little cellular material. The leukocyte count is usually less than 1.0 X 109/L and the erythrocyte count is less than 100.0 X 109/L.  The leukocytes that are present consist of monocytes and lymphocytes.
  • 181.  Exudates will generally appear cloudy or turbid.  May appear yellow, brown, greenish, and even bloody.  In some instances they may even be clotted due to the presence of fibrinogen  The leukocyte count will usually be greater than 1.0 X 109/L and include neutrophils, lymphocytes, monocytes, eosinophils , and even basophils.
  • 182.
  • 184. Composition  Mucopolysaccaride  0.9% hyaluronic acid – most important. Functions in lubricating the joints  Albumin  Globulin  Glucose  Lipids  Nonprotein nitrogenous substances
  • 185. Enzyme content  Alkaline phosphatase  Acid phosphatase  Lactic dehydrogenase
  • 186. Function  Supply nutrients to cartilage  Act as lubricant to joint surfaces  Carry away waste products
  • 187.  String Test- viscosity and clarity of the fluid can be examined. Tests Viscosity Clarity Normal Fluid When dropped from a Transparent & colorless- syringe, forms a string of light yellow greater than 10-15cm Inflammatory Fluid Low viscosity & flows like Cloudy & yellow/green H20 Non-inflammatory Fluid Clear & yellow Haemorrhagic fluid Cloudy & red/ red-brown *Normal synovial fluid is clear, pale, yellow, viscid, and does not clot
  • 188. Chemical Tests  Glucose- typically a bit lower than blood glucose levels. May be significantly lower with joint inflammation and infection.  Protein- increased with bacterial infection  Lactate dehydrogenase- increased level may be seen in rheumatoid arthritis, infectious arthritis, or gout.  Uric acid- increased with gout
  • 189. Microscopic Examination  Total cell count- number of RBC’s and WBC. Increased WBC may be seen in infections such as gout & rheumatoid arthritis.  WBC differential- determines the percentages of different types of WBC.  ↑ neutrophil- seen with bacterial infections  Greater that 2% eosinophil- suggest Lyme disease
  • 190. Clinical Disorders  Increase volume of the synovial fluid results in a variety of pathological process  Non-inflammatory- Osteoarthritis, neuroarthropathy  Inflammatory- rheumatoid arthritis, gout  Septic- Bactericidal or fungal infection  Haemorrhagic- Haemophilia or trauma
  • 191. Tears
  • 192.
  • 193. Enzyme content  Tears secreted by the lacrimal gland contains the enzyme lysozyme which protects the cornea from infection by hydrolyzing the mucopeptide of the polysaccharide cell walls of many microorganisms.
  • 194. Function  Keeps the epithelium moist, thereby protecting the outer covering of the eye from damage due to dryness  Creates a smooth optical surface on the front of the cornea  Acts as the main supplier of oxygen & other nutrients to the cornea  Carries waste products from the cornea  Improves the quality of retinal image by smoothing out irregularities of the cellular surfaces  Provide enzymes that destroy bacteria that can harm the eye
  • 196. Schirmer Test  Determines whether the eyes produces test enough to keep it moist  This test is used when a person experiences very dry eyes or excessive watering of the eyes  Performed by placing filter paper inside the lower lid of the eye & after a few minutes, the paper is removed & tested for moisture content.  Flourescein eye drops are also used to test if tears can flow through the lacrimal ducts into the nose More than 10 mm of moisture on the filter paper in 5 minutes is normal
  • 197. Meniscometry  Meniscometry is a minimally invasive test, which is particularly useful in assessing tear volume indirectly by measuring tear meniscus radius.  The smaller the radius of curvature, the smaller the volume of tears present and the greater the capillary suction of fluid back into the menisci from the tear film.
  • 198. Clinical Disorders  Crocodile tears syndrome  Keratoconjunctivitis sicca
  • 199. Crocodile Tears  An uncommon consequence of nerve regeneration subsequent to Bell's palsy or other damage to the facial nerve in which efferent fibers from the superior salivary nucleus become improperly connected to nerve axons projecting to the lacrimal glands (tear ducts), causing one to shed tears (lacrimate) during salivation while smelling foods or eating.
  • 200. Keratoconjunctivitis sicca  Dry eye syndrome  A relativelycommon condition, especially in older patients, that is characterized by inadequate tear film protection of the cornea because of either inadequate tear production or abnormal tear film constitution, which results in excessively fast evaporation or premature destruction of the tear film.
  • 201. Human Breast Milk  Composition & Function  Fats  Needed for the development of nervous system  Insulation & component of cell membrane Lipid (grams/100ml milk) 4.38 FA (8C) trace PUFA 0.6(14%)  Carbohydrates  Provide energy (lactose is the predominant carb.) Carbohydrate (grams/100ml milk) lactose 7 oligosaccharides 0.5
  • 202. Human Breast Milk  Proteins  Needed for protein synthesis for growth & development  Composed mostly of whey (60%-80%) & casein Protein (grams/100 ml milk) 1.03 casein 0.3 a-lactalbumin 0.3 0.3 lactoferrin 0.2 IgA 0.1 IgG 0.001 0.001 lysozyme 0.05 serum albumin 0.05 ß-lactoglobulin -  Contains lactoferrin that has bacteriostatic effect  Contains antibodies, bifidus factor & digestive enzymes
  • 203. Human Breast Milk  Vitamins, minerals and other nutrients  Contains a host of vitamins, minerals and other nutrients that support a host of different biochemical processes essential for life Ash (%) 0.20 Riboflavin (mg) 0.036 Calcium (mg) 25-35 Niacin (mg) 0.177 Iron (mg) 0.03 Pantothenic acid 0.223 Magnesium (mg) 3 Vitamin B6 (mg) 10 Phosphorous (mg) 13-16 Folacin (mg) 5 Potassium (mg) 51 Vitamin B12 (mcg) 0.045 Sodium (mg) 17 Vitamin A (mg) 58 Zinc (mg) 0.17 Vitamin D (mg) 0.04 Ascorbic acid (mg) 5 Vitamin E (mg) 0.34 Thiamine (mg) 20 Vitamin C (mg) 4
  • 204. Human Breast Milk  Control mechanism  Lactogenesis  Transforms a mammary gland from its undifferentiated state to fully differentiated state in late pregnancy  Stage I – occurs in mid-pregnancy  ↑ in lactose, total protein and immunoglobulins  ↓ in Na+ and Cl-  Stage II – onset of milk secretion  ↑ in lactose (further increase) and citrate
  • 205. Human Breast Milk  Control mechanism  Lactation  Abrupt ↓ in progesterone (removal of placenta) initiates milk secretion  Prolactin  Stimulates and maintains mammary glandular ductal growth and milk protein synthesis  Oxytocin  Promotes “milk let-down” reflex
  • 207. Human Breast Milk  Enzymes  Lipase  For fat breakdown  Lactoperoxidase and lysozymes  Bactericidal effect  Other enzymes  Transport moieties for other substances such as zinc, selenium & magnesium
  • 208. Human Breast Milk  Diseases associated with breastmilk  Mastitis  infection of the tissueof the breast that occurs most frequently during the time of breastfeeding  causes pain, swelling, redness, and increased temperature of the breast  occurs when bacteria, often from the baby's mouth, enter a milk duct through a crack in the nipple  Resolves through antibiotic medication
  • 209. Human Breast Milk  Subareolar abscess  abscess or growth on the areolar gland, which is located in the breast under or below the areola  cause is blockage of the small glands or ducts under the areola, with development of an infection under the skin  Symptoms may occur as:  Drainage and possible pus from lump beneath areolar area  Fever  General ill-feeling  Swollen, tender lump beneath areolar area  Treatment done with antibiotics
  • 210. Human Breast Milk  Duct ectasia syndrome  occurs when a milk duct beneath nipple becomes dilated → duct walls thicken → duct fills with fluid → milk duct can then become blocked or clogged with a thick, sticky substance  usually improves without treatment  Antibiotics or surgery only instituted if signs/symptoms persist  Tenderness in the nipple or surrounding breast tissue  Redness  A lump or thickening  An inverted nipple
  • 211. Human Breast Milk  Breast engorgement  can occur due to :  sudden increased milk production that is common during the first days after the baby is delivered  when the baby suddenly stops breastfeeding either because it is starting to eat solid foods or it is ill and has a poor appetite  may also be caused when the mother does not nurse or pump the breast as much as usual  alveoli become over-distended which can lead to the rupture of the milk-secreting cells  can lead to cessation of milk production  Severe engorgement of the breast can lead to breast infection
  • 212. Human Breast Milk  Current research for breast milk testing  breast milk could be used to predict whether she is at risk of developing breast cancer, according to scientists  Cells in the milk can easily be tested to see if they contain certain genes linked to the illness  the DNA of the milk appears altered to those who have shown to be (+) to cancer as evidenced by their respective biopsies
  • 213. Sweat  Composition  Highly variable, but Na+ and Cl- are the major electrolytes  Mineral composition varies depending on the person’s activity  sodium (0.9 gram/liter)  potassium (0.2 g/l)  calcium (0.015 g/l)  magnesium (0.0013 g/l)  zinc (0.4 milligrams/liter)  copper (0.3–0.8 mg/l)  iron (1 mg/l)  chromium (0.1 mg/l)  nickel (0.05 mg/l)  lead (0.05 mg/l)
  • 214. Sweat  Function  produced by glands in the deeper layer of the skin, the dermis  main function is to control body temperature  additional function of sweat is to help with gripping, by slightly moistening the palms
  • 215. Sweat  Enzyme  Contains cysteine proteinase inhibitors  inhibits papain which is known to cleave the Fc portion of immunoglobulins
  • 216. Sweat  Test  Sweat Chloride Test  common and simple test used to evaluate a patient who is suspected of having cystic fibrosis (CF)  iontophoresis is employed to produce the necessary volume of sweat for the test  normal sweat chloride = 10-35 mEqs/l  sweat chloride value < 60 mEqs/l is indicative of CF  Those having intermediate values are advised to have the test repeated on a periodic basis
  • 217. Sweat  Diseases associated with sweat  Hyperhydrosis  abnormal increased sweating  In most cases, cause is unknown. In some cases, however, causes are:  Obesity  Hormonal changes associated with menopause (hot flushes)  Illnesses associated with fever, such as infection or malaria  An overactive thyroid gland (hyperthyroidism)  Diabetes  Certain medications
  • 218. Sweat  Idiopathic hyperhydrosis  most common form of excessive sweating  Cause is unknown  can develop during childhood or later in life  can affect any part of the body, but the palms and soles or the armpits are the most commonly affected  occurs even during cool weather, but it is worse during warm weather and when a person is under emotional stress
  • 219. Sweat  Apocrine bromhidrosis  most prevalent form of bromhidrosis  bacterial decomposition of apocrine secretion contribute to its pathogenesis  yields ammonia and short-chain fatty acids having strong odors
  • 220. Sweat  Eccrine bromhidrosis  Happens when eccrine sweat softens keratin  bacterial degradation of the keratin yields a foul smell  Can be caused by ingestion of some foods or drugs like:  Garlic  Onion  Curry  Alcohol  certain drugs (eg: penicillin, bromides)
  • 222. Mechanisms of Detoxification • Primarily a function of the liver • Has 2 phases • Phase I • Directly neutralizes or converts a substrate into an intermediate one. • Phase II • Renders a non-toxic final product.
  • 223. Phase I  Involves a group of enzymes – cytochrome P450 family  Uses O2 and NADH as a cofactor  Employs varied reactions depending on the substrate to be detoxified  Free radicals are produced in the process
  • 225. Phase I  Some substances that can cause overactivity of cytochrome P450 enzymes:  Caffeine  Alcohol  Pesticides  Sulfonamides  Barbiturates
  • 226. Phase I  Phase I can directly neutralize some chemicals like:  Caffeine
  • 227. Phase I  Overactivity of Phase I  Leads to wide range of chemical tolerances  Depletion of antioxidants  Accumulation of intermediate substance  Predisposition to liver cell damage  Underactivity of Phase I  Low tolerance to wide range of chemicals  Longer detoxification time
  • 228. Phase I  Inducers of Phase I  Foods from brassica family  Cabbage, broccoli, Brussels sprouts  Also stimulates Phase II detoxification pathway  Contains Indole-3-carbinol, a powerful anti-cancer  Citrus fruits  Oranges, lemons and tangerines  Contains limonene that is a strong inducer of Phase I & II
  • 229. Nutrients  Niacin, vitamin B1, vitamin C  Herbs  Caraway and dill seeds
  • 230. Phase I  Inhibitors of Phase I  Drugs  benzodiazepines; antihistamines; cimetidine; ketoconazole  Foods  naringenin from grapefruit juice  curcumin from turmeric  capsaicin form chili pepper  eugenol from clove oil  quercetin from onions  Aging
  • 231. Phase II  Involves conjugation reactions to neutralize toxins  Essentially, there are 6 pathways  Glutathione conjugation  Amino acid conjugation  Methylation  Sulfation  Acetylation  Glucuronidation
  • 233. Phase II: Glutathione conjugation  Produces water-soluble mercaptates with the help of enzyme GST
  • 234. Phase II: Amino acid conjugation  Amino acids take on the action of neutralizing toxins  Glycine is the most commonly used AA in Phase II AA detoxification
  • 235. Phase II: Methylation pathway  involves conjugating methyl groups to toxins  methyl groups come from S-adenosyl methionine (SAM)  synthesized from methionine
  • 236. Phase II: Methylation pathway  Inactivates drugs through methylation like estrogens
  • 237. Phase II: Sulfation pathway  conjugation of toxins with sulfur-containing compounds
  • 238. Phase II: Sulfation pathway  Main pathway for detoxification od steroids and thyroid hormones  Primary route for elimination of neurotransmitters
  • 239. Phase II: Acetylation pathway  Conjugation of toxins with acetyl-CoA  Primary elimination of sulfa drugs  Detoxifies many environmental toxins, including tobacco smoke and exhaust fumes
  • 240. Phase II: Glucuronidation pathway  Combines glucuronic acid with toxins  requires the enzyme UDP-glucuronyl transferase (UDPGT)  major inactivating pathway for lots of toxins
  • 241. Phase II: Glucuronidation pathway  Glucuronidation of Etoposide
  • 242. Phase II  Inducers of Phase II  Glutathione conjugation:  Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil)  Amino acid conjugation:  Glycine  Methylation:  Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12)
  • 243. Phase II  Inducers of Phase II  Sulfation:  Cysteine, methionine, taurine  Acetylation:  most vegetables and fruits but especially cruciferous vegetables  Glucuronidation:  Fish oils, limonene-containing foods
  • 244. Phase II  Inhibitors of Phase II  Glutathione conjugation:  Selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency  Amino acid conjugation:  Low protein diet  Methylation:  Folic acid or vitamin B12 deficiency
  • 245. Phase II  Inhibitors of Phase II  Sulfation:  Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), molybdenum  Acetylation:  Vitamin B2, B5, or C deficiency  Glucuronidation:  Aspirin, probenecid

Notas do Editor

  1. Nephrogenic diabetes insipidus, which involves the inability to concentrate urine or adjust to subtle changes in extracellular fluid osmolarity, results from the unresponsiveness of renal tubular osmoreceptors to ADH.
  2. Dipole refers to unequal sharing of electrons in a chemical compound. A polar molecule has unequal sharing, where one side is more charged, such as water, the oxygen is negatively charged, and the hydrogen positive.A molecule with electrical charge distributed aymmetrically about its structureMaterials with a high dielectric constants are good insulators
  3. Stomach -&gt; HCl (parietal cells, decreases pH)  needed by pepsinogen to be converted into pepsinMouth – carbohydrate digestionProtein – start in the stomach, due to pepsin and intrinsic factors (reabsorption vit B12)Mucus barrierGastrin controls secretionGastric emptying – increased by gastroenterogens???
  4. Pancreatitis – due to the activation of zymogens
  5. Bilirubin predominates
  6. Maximum volume that the gallbladder can hold is only 30 to 60 milliliters.
  7. &gt;By far the most potent stimulus for causing the gallbladderContractions is the hormone cholecystokinin&gt;Sphincter of oddi guards the exit of the common bile duct into the duodenum.
  8. &gt; It is important in the digestion and absorption of lipids&gt;form micelles - with the hydrophobic sides towards the fat and hydrophilic towards the outside
  9. Pancreatic problem – no absorption of ADEKBile – cholesterol, bile pigments, salts (must have equal concentrations) Imbalance: increase cholesterol  bile stones
  10. Iron and most soluble proteins is absorbed in Duodenum Bile acids are absorbed in terminal ileum
  11. &gt;Quite turbid because of the presence of &gt;Nacl. Sodium bicarbonate, other inorganic salts&gt;neutralize the acid chyme from stomach&gt;ex. saccharidases, maltase, sucrase, lactase split saccharides, maltose, sucrose and lactose respectively
  12. Despite this, water makes up about 70% of the fecal weight.
  13. *Since the large intestine can only absorb about 8 liters of water in a day.
  14. Separate hard lumps, like nuts (hard to pass).2. Sausage-shaped but lumpy.3. Like a sausage but with cracks on its surface.4. Like a sausage or snake, smooth and soft.5. Soft blobs with clear cut edges (passed easily).6. Fluffy pieces with ragged edges, a mushy stool.7. Watery stool, entirely liquid.&gt;&gt;&gt;&gt;&gt;Types 1 and 2 indicate constipation, with 3 and 4 being the &quot;ideal stools&quot; especially the latter, as they are the easiest to pass, and 5–7 being further tending towards diarrhea or urgency.
  15. While the concentration of glucose in a fluid does not necessarily help to determine if a fluid is a transudate or an exudate, it can help determine what might be causing an exudate.
  16. Sodium potassium chlorine Low levels of magnesium and calcium
  17. More casein than whey in infant formula milkWhey softens stools
  18. Tanner 3 – milk production; due to ductile and lobular differentiationCitrate increases when it is near delivery
  19. Contraction of myoepithelial cells (a fxn of oxytocin)