History: Toxin (Stinger)  APC  MHC  T cell activation (CD8,CD4)  B CELL

(antigen presenting cells) (major histocompatibility complex)

Histamine  Mast Cells (IgE) Histamine Receptors

3 Types Histamine Receptors:

a. H1
b. H2
c. H3

H1  Bronchi  Broncho-Constriction

a. Obstruction Airflow (PATENCY)

PaCO2  increase and PaO2 decreases

CO2 (BLOOD) + H20  Carbonic Anhydrase  H+ + Carbonic Acid.

Increases H+  decreases pH  ACIDOSIS

Effects of acidosis:
1. Increase cell membrane permeability
a. cellular swelling  Edema damage the cellular elements  Ischemia/death
b. K+ leak Hyperkalemia  Cardiac Arrhythmia (cardiac arrest)

2. H+ ion is increased  CHEMORECEPTORS are Stimulated  Depolarize VN/GN

1. Arch of the Aorta  VAGUS NERVE
2. Carotid Sinus GLOSSOPHARYNGEAL NERVE

VN /GN tracus solitaries  MEDULLA OBLONGATA (DRG/VRG)  INCREASE IN VENTILLATION RATE

Chemo receptor reflex activation  H+  Stimulation  Medulla Oblongata VRG/DRG

 Increasing Respiratory Rate

1. Atelectasis (Obstructive)

2. DOB & Respiratory Distress

PaO2  decrease  E reduced

Stridor  Upper Airway (Laryngeal Edema) & Wheeze

 Hyper-secretion Mucus

Blood Vessels:

a. Vasodilation 

1.Increased blood flow (Peripheral not in central)

2. Decrease BP

a. Baroreceptor reflex activation  TACHY

H2  Parietal cell  Hyperacidity

H3  CNS/ CN 8  Vertigo

Adrenergic Receptors:
1. Sympathetic
2. Sympathetic nerve
3. NOREPI, EPI, DOPAMINE  Primary Neurotransmitter

Drugs that stimulates the Adrenergic Receptors  SYMPATHOMIMIMETIC

Drugs that blocks the Adrenergic Receptors  SYMPATHOLYTIC AGENTS

Alpha receptors
Alpha 1 Blood vessel VASOCONSTRICTION :
- Decrease blood flow
- Increase BP
Alpha 2  Coronary Arteries (Vasodilation effect)

Beta 1 Heart (R side Heart), JG cell, Uterus, Islets of Langerhans (Alpha & Beta Cell)

1. Tachycardia
2. Renin Release  ANGIOTENSINOGEN activation  ANGIOTENSIN 2 ( AT1 receptors)
a. Aldolsterone release  Water Retention (Reabsorbing Na+ & H2O but K+ Loss)
b. Potent Vasoconstriction
c. Cardiac Remodeling
3. Relaxation Uterus (B1)
4. Inhibition of Insulin Release  Hyperglycemia (Mimic Glucagon Activation)
5. Adipose Tissue

Beta 2 bronchi  Bronchodilation

Hydrocortisone (steroid/glucocorticoid)  DRUG

Cortisol  Adrenal Cortex (Zona glomerulosa)
Phospholipase A2 :  Arachidonic Acid
1. Cyclooxigenase Pathway
a. COX1
- TXA2 : (POTENT VASOCONSTRICTOR, PLATELET AGGREGATOR)
- Prostacycline: (NO  VASODILATOR)
- PGE1
b. COX2
- PGE2
- Bradykinin
2. Lipooxygenase Pathway  ALLERGIC ACTIVITY
a. Immune Modulating Action (Immunostimulant)
-Leukotriens (LTD1, LTD2)
-Cellular Differentiation, Chemotaxis, Chemical Release
- APC, WBC, Tcell
b. Mast Cell  Release Histamine
1. Inhibit Phospholipase A2

Prostaglandin (PGE1)
a. Increases Cell membrane permeability  Fluid Leak  cellular swelling/edema
b. Increases Body Temp/Fever  is the one stimulates your thermoregulating center(hypothalamus)
a. Infection  cell membrane bacteria Endotoxin (G+)  TNF alpha  Travels in the
hypothalamal artery of hypothalamus  release PGE in the endothelium of the blood
vessel wall.
TNF alpha  TUMOR NECROSIS FACTOR ALPHA
b. Immunomodulating Event  Damage Cell membrane  Release TNF alpha  hypothalamal
artery  PGE activation  thermoregulating center activation.
c. Pain  Serves as Chemoattractant for Nociceptor activation (capsacin enzyme)  converts
chemical/mechanical/sensory stimulation from nociceptor to electrical signal.
d. Uterine Contraction
e. GMB (Gastric Mucosal Barrier)  limiting the direct contact of HCL
a. It prevents damage in the mucosa of stomach
b. Vasodilating action in the mucosal cell  Increase blood mucosa (HEALING)

Lipooxygenase Pathway: (ALLERGIC REACTION)

1. Induces the release Leukotrines (LTD1, LTD2)  Modulates Immuno-surveillance  Hyperstimulation

immune response (Differentiation, Chemotaxis, Chemical realese)
2. HISTAMINE RELEASE  H1, H2, H3

Muscarinic Receptors (Cholinergic Receptors)

1. Vagus nerve
2. AcH
3. Parasympathetic
M1  CNS  CTZ activation  N&VOMITING
M2  Heart (L side of Heart)  BRADYCARDIA
M3:
1. LES  Relaxation of the LES
a. Bolus entry
b. GERD (Patho) REFLUX OF ACID CAN OCCUR
2. Parietal Cell Stomach  Hypersection of HCL
a. Nicotine
b. Caffeine
c. Ach of Vagus nerve (Cephalic Phase)
3. Intestine  Ach  Stimulate Smooth Muscle of the Intestine  Peristalsis  Magtatae
4. Bronchi  Bronchoconstriction
5. Mucus cells & Goblet Cells  Hypersection (Parotid/Maxillary Glands)
6. Skeletal Muscle  Contraction
7. Pupil  Constriction

M4  CNS  Temporal Lobe  MEMORY

Acetylcholine Synthesis:
1. Presynaptic Cleft
a. Acetate  (Mlitochondria, kreb cycle)
b. Choline (Recycle )
c. Acyl-0-transferase enzyme(Choline-o-acyltransferase) (ACETATE +CHOLINE  Acetylcholine)
Acetylcholine Release:
1. Calcium Calcium Voltage Gated Ion Channel (Presynaptic Cleft)
- opens only in the presence electrical energy (-90mV)
- Calcium Enters & binds  SYNAPTOTAGMIN
- Vesicle containing neutransmitter (quanta) move to the direction of the presynaptic membrane
- Vesicle binds to the docking receptor
- Exocitosis (Mediated by calcium)  neutransmitter realease

Postsynaptic Cleft Activation:

1. Binding of Ach to M receptor/AcH Receptor  Depolarization of cell membrane  FUNCTION

AcH Degradation:
1. Circulating AcH  bind to the AcHE
Acetylcholine AcHE  ACETATE + CHOLINE
ACETATE will be degraded, Choline  Reabsorbed in the Presynaptic Cleft

Baygon  Insecticide
 Inhibits Acetylcholinesterase (AChE)
Atropine Sulfate  Muscarinic Receptor Blocker (M1-M4)
1. Preoperative Medication
2. Resuscitation Sp. Bradycardia (cardiac block)
3. Dilate Pupils  Before OR (Glaucoma Surgery)
4.Bronchodilation (Combivent/Ipratropium Hbr)
Where does Ammonia came from?
1. PROTEIN (Amino Acids)
- AST
- ALT

2. Ammonia Degradation
a. Ammonia is liphophillic  It can pass through to cell membrane, easily reabsorb & very difficult to
remove in the body (Liver role is to convert ammonia into water soluble via CARNITINE/UREA Cycle)
Ammonia  Urea (Easily secreted and excreted in urine, feces)

LACTULOSE:
- Increases the bulk fecal material & attracts water  Intestinal Distension  Local Vagal
Stimulates  Increase Peristalsis TATAE
- TUMAE  kasama UREA, bacterial forming urease
Urease  Urea to Ammonia
- Ammonia reabsorbed increase level (Hepatic Encephalopathy) in the blood and can pass through
BBB 
- Ammonia prevents conversion of alpha ketoglutarate ( this is essential for the kreb cycle  Energy
production for ATP release) , this pushes the conversion to GLUTAMATE.
- Net effect lost of energy supply in the brain  Lactic acidosis  Cerebral Edema  Hallucination
& Neural deficits such as flapping hands.