Body FluidsSection A, Group 2ALFONSO, ALJAMA, ALUZANAMURAO, 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 der Waals 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 fluid intake 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 evenly distributed 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 lysozyme3. 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

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)

Composition: Organic Constituents

Gastric Juice

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

Enzyme Content

Gastric Juice

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)

Enzyme Content

Gastric Juice

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

Control Mechanism: SECRETION

Gastric Juice

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

Control Mechanism

Gastric Juice

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).

Control Mechanism

Gastric Juice

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)

Control Mechanism

Gastric Juice

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.

Control Mechanism: INHIBITION

Gastric Juice

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

Control Mechanism: INHIBITION

Gastric Juice

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

Functions

Gastric Juice

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

Tests

Gastric Juice

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

Clinical Disorders

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

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

Composition

Pancreatic Juice

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

Enzyme Content

Pancreatic Juice

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

Enzyme Content

Pancreatic Juice

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

Enzyme Content

Pancreatic Juice

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

Control Mechanism

Pancreatic Juice

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

Control Mechanism

Regulation of Pancreatic Secretion

Pancreatic Juice

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

Control Mechanism

Pancreatic Juice

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

Functions

Pancreatic Juice

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

Tests

Pancreatic Juice

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

Tests

Pancreatic Juice

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.

Clinical DIsorders

Pancreatic Juice

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

Clinical DIsorders

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, and absorption of fats.

Bile Composition Water (85%), bile salts (10%),(Cholic, chenodeoxycholic,

deoxycholic, 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 (Brown)

Urobilinogen (colorless)

Bilirubin(red)

Biliverdin (green)

Bile SecretionRelease of hormone secretin and CCK

(chocystokinin) from the duodenum increase bile

secretion

Bile is subsequently stored & concentrated in the gallbladder between

meals

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 GallbladderGallbladder begins to

empty, when food (fatty foods) reach the

duodenum about 30 minutes after a meal*

Gallbladder emptying is rhythmical contractions of

the gallbladder*

Effective emptying requires simultaneous

relaxation of sphincter of oddi*

Bladder bile vs. Liver bileConstituent Bladder bile (%) Liver bile (%)

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 lipids 0.5-4.7 0.2-0.4

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

1.5% Solid components* 8.3 pH*

Organic material eg. mucoproteins

and enzyme*

Feces Formation and CompositionFeces 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 Chart or 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)

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

Characteristics of urine under physiological conditions

Characteristics

Color Amber Pigment: urochrome Other pigments:

uroerythrin, uroporphyrins, riboflavin

Odor Does not have unpleasant

smell (aromatic) Other odors arise from food Mercaptan-like odor after

eating asparagus Oil of wintergreen (has

methyl salicylate) strong odor of evergreens

Turbidity Urine is clear and

transparent After standing for a long

time flocculent material (mucoprotein + nucleoprotein + epithelial cells) separates

pH Varies from 4.6 to 8.0 Protein diet gives rise to

acidic pH oxidation of sulfur in sulfur containing amino acids into sulfuric acid

Vegetable and fruit diet gives rise to alkaline urine

Urine samples taken right after eating meals are alklalinesecretion of H+ in the gastric juice

Ions in the urine Anions The major anion is chloride The amount is equal to the

amount that was ingested In salt-poor diets, Cl- may be

absent

Cations Sodium and potassium are

the major cations Total excretion of Na+ varies

between 2.0 and 4.0 g/day K+ 1.5 to 2.0 g/day.

Nitrogenous organic compounds Urea α the total nitrogen

intake Uric acid – end product of

purine metabolism; α purine intake

Creatinine α muscle mass Creatine predominant in

children and pregnant women

Hippuric acid - formed in the liver

Indican – potassium salt

Component AmountUrea 12 to 36 g per

day (70-g adult)

Uric acid 0.7 g of uric acid per day

Creatinine (coefficient)

18 to 32 and 10 to 25 in women

Hippuric acid 0.7 g per dayIndican 5 to 25 mg per

day

CompositionComponent Concentration in

urine (mg percent)Concentration in

blood (mg percent)[U]/[P]*

Urea 2000 30 67Uric acid 60 2 30

Creatinine 75 2 37Indican 1 0.05 20

Phosphate 150 3 50Sulfate 150 3 50

Potassium 150 20 7.5Chloride 500 350 1.4Sodium 350 335 1Calcium 15 10 1.5

* Concentration in urine / concentration in blood plasma

Normal concentration of organic compounds, anions, and cations in urine

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 Occurs after eating unusual

amounts of fruits and fruit juices

Idiopathic pentosuria – occurs in the absence of L-xylulose dehydrogenase (a genetic disease) Xylulose is excreted in the

urine

Tests for pentosuria Benzidine + acetic acid +

urine mixture is heated then cooled rose-pink color (+ for pentose)

(+) Benedict’s reagent (-) baker’s yeast

fermentation

Lactosuria Moderate amounts of

lactose secretion is found in lactating women Does not occur in

pregnancy

Tests for lactosuria (+) baker’s yeast

fermentation (+) mucic acid test (-) Barfoed’s test Yields lactosazone

Fructosuria Occurs in association with

diabetes mellitus The site of difficulty is the

liver (it’s where fructose is stored as glycogen

There is a deficiency in the enzyme fructokinase

Tests for fructosuria (+) Benedict’s reagent (+) baker’s yeast

fermentation Yields glucosazone and

phenylhydrazine

Galactosuria A consequence of

galactosemia Galactose is not detectable

in the urine prior to the introduction of milk in the diet

Tests for galactosuria reduction of alkaline copper

solutions slight fermentation by

baker’s yeast (+) Barfoed’s test (+) mucic acid test.

Proteinuria presence of proteins, most

especially albumin, in the urine.

Plasma proteins may pass damaged renal epithelium

Tests for Proteinuria Nitric acid ring test Sulfosalicylic acid test –

degree of turbidity (+) Heat and acetic acid test –

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

Body Fluid

Lymph

The lymphatic system maintains volume and pressure of the extracellular fluid returns excess water and dissolved substances

from the interstitial fluid to the circulationLymph 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.

CompositionLymph 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 As it flows through the lymph nodes it comes in

contact with blood, and tends to accumulate more cells (particularly, lymphocytes) and proteins.

An edema that is caused by the blockage of lymph return

Body Fluids

Cerebrospinal fluid

CSF functions in protecting the brain from sudden

changes in pressures.Maintaining a stable environment removing waste products of the cerebral

hemisphere.

Production of CSFchoroid plexus

in the ventricles

cisternae subarachnoid space

arachnoid villi venous blood

P P

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

Characteristics of CSF under physiological conditions

Characteristics

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 ratio)

500:1

IgG index 0.66

Composition

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

• Paretic curve• Fluids with large globulin

content• Such curves are contained in

casese with general paralysis• Multiple sclerosis, lead

poisoning with brain involvement

Done by mixing decreasing dilutions of CSF with colloidal gold solution Normal CSF causes no

change in the appearance of the orange-red colored solution

Fluids with pathologic conditions produce color change depending on the condition and dilutiona

Luetic curve Fluids with limited globulin

and moderate albumin content Certain forms of cerebro-spinal

syphilis Also in brain tumor,

poliomyelitis, and cerebral arteriosclerosis

• Meningitic curve• Large amounts of globulin and

globulin• All meningitic conditions show

this kind of curve

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

Tests String Test- viscosity and clarity of the fluid can be examined.

Viscosity Clarity

Normal Fluid When dropped from a syringe, forms a string of

greater than 10-15cm

Transparent & colorless- light yellow

Inflammatory Fluid Low viscosity & flows like H20

Cloudy & yellow/green

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 relatively common

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

Carbohydrates Provide energy (lactose is the predominant carb.)

Lipid (grams/100ml milk)FA (8C)PUFA

4.38trace

0.6(14%)

Carbohydrate (grams/100ml milk)lactose

oligosaccharides

70.5

Human Breast Milk Proteins

Needed for protein synthesis for growth & development Composed mostly of whey (60%-80%) & casein

Contains lactoferrin that has bacteriostatic effect Contains antibodies, bifidus factor & digestive enzymes

Protein (grams/100 ml milk)casein a-lactalbumin 0.3 lactoferrin IgA IgG 0.001 lysozyme serum albuminß-lactoglobulin

1.030.30.30.20.1

0.0010.050.05

-

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 (%) 0.20Calcium (mg) 25-35Iron (mg) 0.03Magnesium (mg) 3Phosphorous (mg) 13-16Potassium (mg) 51Sodium (mg) 17Zinc (mg) 0.17Ascorbic acid (mg) 5Thiamine (mg) 20

Riboflavin (mg) 0.036Niacin (mg) 0.177Pantothenic acid 0.223Vitamin B6 (mg) 10Folacin (mg) 5Vitamin B12 (mcg) 0.045Vitamin A (mg) 58Vitamin D (mg) 0.04Vitamin E (mg) 0.34Vitamin 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 tissue of 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