Microbial Interactions with Humans

Microbial Interactions with Humans

Types of Interactions: Symbiosis
* Symbiotic Relationships

Overview of Human-Microbial Interactions
* Pathogens
* Pathogenicity
* Virulence
* Opportunistic Pathogen

Infection Versus Disease
* Infection
* Disease

Opportunistic Pathogens
* Don’t normally cause disease, but may under some circumstances
* 3 circumstances for gaining control/disease

Types of Interactions:
Normal Flora
* Normal Flora
* Factors that influence normal flora

Normal Flora
* Hundreds of different niches associated with human
* Some normal flora are pathogenic
* Resident versus transient flora
* Considered part of the first line of defense!
* Microbial antagonism
* Competitive exclusion

Portals of Entry
* Skin
* Mucous membranes

Preferred Portal
* Many microorganisms have to enter in a specific way and in a certain place to cause disease.
* Skin Portal

Skin
* Epidermis and Keratin
* Hair often deters microbial contact with skin
* Dermis and subcutaneous tissue
* Apocrine and sebaceous glands
* Eccrine glands (sweat)

Skin as a Barrier
Mucous Membranes
* Found in mouth, pharynx, esophagus, GI, respiratory, and urinary tracts
* Epithelial cells coated with protective glycoprotein layer (mucous)
* Less protection than skin
* Cilia and mucous produced by goblet cells

Mucous Membranes
* Respiratory tract Portal
* Respiratory Normal Flora
* Respiratory Barrier Mechanisms
* Gastrointestinal tract portal
* GI Normal Flora

Gastrointestinal Tract
* Large intestine
* GI Barrier
* Genitourinary tract Portal
* Genitourinary Tract Normal Flora
* Genitourinary Tract Barrier

LD50 and ID50
* LD50: Number of microbes in a dose that kill 50% of the organisms infected in a sample
* ID50: Number of microbes in a dose that causes disease in 50% of the organisms infected
* The higher the virulence the lower the ID50 or LD50

Microbial Virulence
Microbe Versus Host
* To cause disease a microbe must…
* Why it is difficult for microbes…
o Skin, antimicrobial sweat
Microorganisms and Mechanisms of Pathogenesis

Line of Defense
* First line: Skin and mucous membranes, normal flora
* Second line: phagocytes, inflammation, fever and antimicrobial substances
* Third line: (specific response) special lymphocytes (B and T cells) and antibodies

Step One: Adherence
* Specific adherence
* Pathogens have attachment structures
* Pathogens have attachment structures

Step 2: Invasion/Colonization
* Increase in numbers beyond the point of attachment.
* Three goals

Step 2: Invasion/Colonization
* Localized versus Systematic infections
* Bacteremia, viremia, toxemia
* Septicemia

Step 3: Cause Damage
* Virulence
* Three Ways to cause damage

Virulence Factors
* Usually help organism colonize and grow
* Coagulase
* Siderophores
* Collagenase
* Protease

Another Way to Classify Exotoxins
* Descriptive classifications
A-B toxin
* Cholera toxin (Vibrio cholera)—cholera

The Action of Chlorea Enterotoxin
More A-B toxin examples
Botulinum Toxin
Tetanus Toxin
Membrane Disrupting Toxins
Superantigens
Endotoxins
* Gram type negatives
* Part of outer portion of cell wall (outer membrane)
* Lipid A portion
* Exert effects when G- microbe lyses
* Same symptoms for different species of microbe
* No antitoxins produced by host
* Very stable—can’t destroy easily
* Rarely fatal
* Disseminated intravascular clotting
* General symptoms

Pyrogenic Response
* Macrophage ingestion
* Release of interleukin-1 in bloodstream
* Interleukin-1 to hypothalamus and production of prostaglandins
* Resetting of bodies thermostat

Susceptibility/Resistance of Host
* Species specificity
* Tissue specificity
* Age
* Stress
* Diet
* Pre-existing disease (Genetic and Infectious)
* Gender
* Behavior
* Weather?
* Your first line of defense—Review this

Microbial Interactions with Humans.ppt

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Lipids

Lipids
By: Henry Wormser, Ph.D.

Introduction
* Definition: water insoluble compounds
+ Most lipids are fatty acids or ester of fatty acid
+ They are soluble in non-polar solvents such as petroleum ether, benzene, chloroform
* Functions
+ Energy storage
+ Structure of cell membranes
+ Thermal blanket and cushion
+ Precursors of hormones (steroids and prostaglandins)
* Types:
+ Fatty acids
+ Neutral lipids
+ Phospholipids and other lipids
Fatty acids
* Carboxylic acid derivatives of long chain hydrocarbons
o Nomenclature (somewhat confusing)
+ Stearate – stearic acid – C18:0 – n-octadecanoic acid
o General structure:
* Common fatty acids
n = 4 butyric acid (butanoic acid)
n = 6 caproic acid (hexanoic acid)
n = 8 caprylic acid (octanoic acid)
n = 10 capric acid (decanoic acid)
* common FA’s:

n = 12: lauric acid (n-dodecanoic acid; C12:0)
n = 14: myristic acid (n-tetradecanoic acid; C14:0)
n = 16: palmitic acid (n-hexadecanoic acid; C16:0)
n = 18; stearic acid (n-octadecanoic acid; C18:0)
n = 20; arachidic (eicosanoic acid; C20:0)
n= 22; behenic acid
n = 24; lignoceric acid
n = 26; cerotic acid

Less common fatty acids
* iso – isobutyric acid
* anteiso
* odd carbon fatty acid – propionic acid
* hydroxy fatty acids – ricinoleic acid, dihydroxystearic acid, cerebronic acid
* cyclic fatty acids – hydnocarpic, chaulmoogric acid

PHYTANIC ACID
A plant derived fatty acid with 16 carbons and branches at C 3, C7, C11 and C15. Present in dairy products and ruminant fats.
A peroxisome responsible for the metabolism of phytanic acid is defective in some individuals. This leads to a disease called Refsum’s disease
Refsum’s disease is characterized by peripheral polyneuropathy, cerebellar ataxia and retinitis pigmentosa
Less common fatty acids
These are alkyne fatty acids
Fatty acids
* Fatty acids can be classified either as:
o saturated or unsaturated
o according to chain length:
Unsaturated fatty acids
* Monoenoic acid (monounsaturated)
Double bond is always cis in natural fatty acids.
This lowers the melting point due to “kink” in the chain
* Dienoic acid: linoleic acid
* Various conventions are in use for indicating the number and position of the double bond(s)
* Polyenoic acid (polyunsaturated)
* Monoenoic acids (one double bond):
* Trienoic acids (3 double bonds)
* Tetraenoic acids (4 double bonds)
* Pentaenoic acid (5 double bonds)
* Hexaenoic acid (6 double bonds)
Both FAs are found in cold water fish oils
Typical fish oil supplements
Properties of fats and oils
* fats are solids or semi solids
* oils are liquids
* melting points and boiling points are not usually sharp (most fats/oils are mixtures)
* when shaken with water, oils tend to emulsify
* pure fats and oils are colorless and odorless (color and odor is always a result of contaminants) – i.e. butter (bacteria give flavor, carotene gives color)
Examples of oils
* Olive oil – from Oleo europa (olive tree)
* Corn oil – from Zea mays
* Peanut oil – from Arachis hypogaea
* Cottonseed oil – from Gossypium
* Sesame oil – from Sesamum indicum
* Linseed oil – from Linum usitatissimum
* Sunflower seed oil – from Helianthus annuus
* Rapeseed oil – from Brassica rapa
* Coconut oil – from Cocos nucifera.....


Websites on lipids

* http://www.cyberlipid.org/ web site deals mainly with an overview on all lipids
* http://www.lipidsonline.org – this website focuses mainly on disease processes (atherosclerosis) and treatment
* http://www.lipidlibrary.co.uk/ -There are two main divisions in this website, one dealing with the chemistry and biochemistry of lipids and the other with the analysis of lipids


Lipids.ppt

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Inborn Errors of Metabolism

Inborn Errors of Metabolism
By:Namrata Singh M.D

Introduction to IEM
* Usually a single gene defect that causes a block in metabolic pathways.
* Problems are because of accumulation of enzyme substrate behind the metabolic block or deficiency of the reaction product.
* In some instances the substrate is diffusible & affects distant organs & in some there is just a local effect ( lysosomal storage disease ).
* Clinical presentation is varied  mild to severe forms ( mutations even in the same gene may be different in different people ).
* Can present at any time.
* Can affect any organ system.

IEM General approach
* DIAGNOSIS : Some clinical presentations:-
o Consider in DDx . when dealing with :-
+ Critically ill infant
+ Seizures
+ Encephalopathy (Reyes like syndrome )
+ Liver disease
+ MR or developmental delay or regression
+ Recurrent vomiting
+ Unusual odor
+ Unexplained acidosis
+ Hyperammonemia
+ hypoglycemia
* Some clues to look for :-
o *Symptoms accompany changes in diet.
o *Developmental regression.
o *History of food preferences or aversions.
o *History of consanguinity in parents.
o *Family history of MR , unexplained deaths in cousins or siblings etc.
* Physical exam:- common findings—
o Alopecia or abnormal hair
o Retinal cherry red spot
o Cataracts or corneal opacities
o Hepatosplenomegaly
o Coarse features
o Skeletal changes ( gibbus)
o Ataxia
o FTT
o Micro or macrocephaly
o Rash / jaundice /hypo or hypertonia
* Lab tests:- almost always needed—
o Serum electrolytes
o Ph ( anion gap & acidosis )
o Se lactate
o Se pyruvate
o Ammonia
o Serum & urine amino acids
o Urine organic acids
o DNA probes
o Glycine in CSF (glycine encephalopathy)
o Urine ketones
+ If + in neonates  IEM
+ If – in older child  IEM ( defect in f.a. oxidation )

IEM – Clinical situations
* MR or dev delay
o Can occur alone.
o Seen in urea cycle ,a.a disorders.
o Also in organic acidemias ,peroxisomal & lysosomal storage disorders.
o Serum & urine a.a .
o Urine for mucopolysacchiduria.
* Ill neonate :-
o Clinically indistinguishable from sepsis.
o Usually disorders of protein & CHO metabolism.
o Acidosis or altered mental status out of proportion to systemic symptoms.
o Labs:
+ Lytes , NH3, gluc , ketones , urine ph ,glycine in CSF.
+ Se & urine for a.a & o.a (* before oral intake is stopped or pt is transfused)

IEM – Clinical situations
* Vomiting & encephalopathy :-
* Hypoglycemia :-
o Seen in fatty acid oxid defects ,glycogen storage diseases ,hereditary fructose intolerance & organic acidemias.
o Other labs:-
Urine ketones ~(+) in GSD & organic acidemias. ~(-) in HFI & f.a. oxidation disorders
o Other labs:-
+ NH3 elevated in organic acidemias & fatty acid oxidation defects.
+ Urine reducing subst.– (+) in galactosemia ,HFI.
+ Urine organic acids
* Hyperammonemia :-
o initially – poor appetite , irritability . Then , vomiting , lethargy , seizures & coma.
o Tachypnea – direct effect on resp. drive.
o Seen in (1)- urea cycle disorders (2)- organic acidemias (3)- transient hyperammonemia of the newborn.
o Resp alkalosis : urea cycle disorders & transient hyperammonemia of newborn.
o Acidosis : organic acidemias

RESP ALKALOSIS
ACIDOSIS
UREA CYCLE DEFECTS
TRANSIENT HYPERAMMONEMIA OF NEWBORN
ORGANIC ACIDEMIAS
SE CITRULLINE—LOW– EARLY UREA CYCLE DEFECT
SLIGHTLY ELEV– TRANSIENT HYPERAMMONEMIA OF NB
MARKEDLY ELEV– CITRULLINEMIA & ARGINOSUCCINIC ACIDEMIA
* Acidosis :-
o With recurrent vomiting.
o With elevated NH3.
o Out of proportion to clinical picture.
o Difficult to correct.
o Seen in organic acidemias , MSUD ,GSD , disorders of gluconeogenesis.
o Increased anion gap (ketoacids ,lactic acid , methylmalonic acid.)

* Acidosis :- additional tests—
o Se glucose
o NH3
o Urine pH
o Ketones
o Amino & organic acids
o Blood lactate & pyruvate
* Lactate & pyruvate—
o Measure in arterial blood.
o Normal Ratio is 10:1 to 20:1.
o High ratio
+ Mitochondrial disorders.
+ Pyruvate carboxylase deficiency.
o Normal or low ratio
+ Glycogen storage disease.
+ Pyruvate dehydrogenase deficiency
* Broad management :-
o Problems severe acidosis , hypoglycemia , hyperammonemia . Can lead to coma & death!
o Stop all oral intake.
o Give I/V glucose to stop catabolism.( most respond favorably to glucose – some do not eg. Primary lactic acidosis in pyruvate dehydrogenase deficiency .)
o Bicarb.
o Hyperammonemia – may need dialysis .
* Specific interventions :-
o Urea cycle disorders-
+ * preventing protein catabolism ( high calorie diet , arginine supplementation )
+ * decreasing NH3 load (protein restriction )
+ * utilizing NH3 scavengers ( benzoate ,phenylbutyrate)
o PKU-
+ *Avoid enzyme substrate in diet.
+ *Diet low in phenylalanine ( Lofenelac , Phenylfree, Analog XP , Maxamaid XP )
+ *Protein restriction.
o Galactosemia-
+ *galactose free diet ( soy formulas contain sucrose rather than lactose )
o Isovaleric acidemia-
+ Pharmacotherapy to remove accumulated substrate –( glycine treatment).
o Methylmalonic acidemia-
+ Provide co-enzyme ( vit B12)
o Gauchers disease-
+ Provide normal enzyme (enzyme infusions)

IEM Some associations
INITIAL FINDINGS ( POOR FEEDING , VOMITING , LETHARGY, CONVULSIONS ,COMA )
METABOLIC DISORDER
INFECTION
OBTAIN PL. NH3
HIGH NORMAL
OBTAIN BLOOD Ph & CO2
ACIDOSIS
NORMAL
UREA CYCLE DEFECTS
ORGANIC ACIDEMIAS
AMINOACIDOPATHIES
GALACTOSEMIA

Inborn Errors of Metabolism.ppt

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