Peptic Ulcer Disease- A review

RECEPTORS

RECEPTORS

 

 

 

 

CONTENTS

1- ENZYME-LINKED RECEPTORS
2- LIGAND GATED ION CHANNELS
3- VOLTAGE GATED ION CHANNELS
4- G PROTEIN COUPLED RECEPTORS
5- NUCLEAR RECEPTOR


 

 

 

 

ENZYME-LINKED RECEPTORS

 

These receptors are themselves enzymatic proteins. The agonist binding site lies on the outer, while the catalytic site lies on the inner face of the plasma membrane. These two domains are interconnected through a single trans- membrane stretch of peptide chain.
Most Enzyme-Linked receptors have tyrosine kinase as the enzyme. e.g. Insulin, epidermal growth factor, platelet derived growth factor & certain interleukins. The intracellular events are triggered by phosphorylation of relevant proteins. The receptor itself gets autophosphorylated on tyrosine residues which promote association of several receptor molecules, organizing the complex signaling mechanisms.

 

LIGAND GATED ION CHANNELS

They regulate the flow of ions across the membranes. Ligand binds and regulates their activity. They are fast acting receptors, respond in sub-milliseconds.
Natural ligands include Ach, Serotonin, GABA & Glutamate.
Neurotransmitter binds to the receptor, altering its concentration to open or close the channel to the flow of Na+, K+, Cl- or Ca++ ions across the membrane.
These receptors mediate neurotransmission, cardiac conduction and muscle contraction.


 


VOLTAGE GATED ION CHANNELS

They transport ions across the membrane and are regulated by the electrical potential difference near the channel. Some are composed in a way that they have a central pore through which ions travel down their electrochemical gradients.
Change in potential induces a conformational change in the channel, it opens admitting the ion influx or efflux to occur across the membrane down the electrochemical gradient.
Example include Na+ and K+ Voltage gated channels
They play role in the generation and propagation of nerve impulse across the membrane.

 


 
G PROTEIN COUPLED RECEPTORS

 
These are a large family of cell membrane receptors which are linked to the effector through one or more GTP-activated proteins.
These receptors comprise a α helical peptide which has seven membrane spanning regions.
The extracellular domain contains a ligand binding area, intracellularly, these are linked to a G protein (Gs,Gq,Gi) having 3 subunits α,β,ϒ, that binds GTP.
Binding of ligand to receptor activates the G protein, which releases GDP & binds GTP.
ADENYLYL CYCLASE (c AMP) PATHWAY
Turned on by Gsà activation of Adenylyl Cyclase àintracellular accumulation of
c AMP à increased Ca++ influx and enzyme activity

 

 
PHOSPHOLIPASE C (IP3-DAG) PATHWAY

Turned on by Gq à activation of Phospholipase C à Generation of IP3 & DAG à

Increased intracellular Ca++ and protein kinase activity

 



NUCLEAR RECEPTOR

 
These receptors work with other proteins to regulate the expression of specific genes.
Ligands include thyroid hormone, heme, cholesterol, Vitamin A & D
Ligand binding to the receptors à translocation from cytoplasm to cell nucleus à binding to nuclear hormone response elementsà resulting in up regulation or down regulation of gene expression
There are 48 known human nuclear receptors, e.g. Thyroid hormone receptor, Retinoic acid receptor, Estrogen receptor

 

Gout

Definition:

Gout is a form of arthritis which is caused by the accumulation of uric acid crystals in joints. In this condition, due to a metabolic dysfunction, there is deposition of uric acid in and around the joints causing severe painfulness, swelling and restricted mobility of the affected joint. 

Gout is a disease that results from an overload of uric acid in the body. This overload of uric acid leads to the formation of tiny crystals of urate that deposit in tissues of the body, especially the joints. When crystals form in the joints, it causes recurring attacks of joint inflammation arthritis. Gout is considered a chronic and progressive disease. Chronic gout can also lead to deposits of hard lumps of uric acid in the tissues, particularly in and around the joints and may cause joint destruction, decreased kidney function, andGout has the unique distinction of being one of the most frequently recorded medical illnesses throughout history. It is often related to an inherited abnormality in the body's ability to process uric acid.

Symptoms:
Gout is an intensely painful condition, which mostly affects only one joint (monoarthritis) at a time, most commonly the big toe. However, Gout may also affect elbows, knees, ankles, wrists or small joints of the hands and feet. The classic history in a patient suffering from Gout is of excruciating and sudden pain, swelling, redness, warmth and stiffness of the joint. Low-grade fever may also be present. The skin overlying the joint can also be swollen, tender and sore if it is touched even lightly. Patients with longstanding hyperuricemia (high levels of uric acid in blood) can have uric acid crystal deposits called tophi in other tissues as well, e.g. the helix of the ear.

Causes of Gout:

Hereditary

Improper function of kidney which results in decreased excretion of urates in urine.

Reaction to alcohol. Reaction to certain drugs, including antibiotics.

Enzyme deficiencies.

Lead poisoning.

Disorder is often associated with an injury or surgical procedure.

Highly proteinous diet.

Unidentified causes—Idiopathic causes.

Starvation—diminished renal excretion of uric acid.

Psoriasis—due to over production of uric acid.

Toxaemia of pregnancy—due to diminished excretion of uric acid. May also occur in some cases of tumors or cancers.

Gout has four distinct stages     

 Asymptomatic: High levels of Uric acid in blood but no joint complaints

Acute phase: Acute complaints described above occur for a brief period

Intercritical phase: There is no pain or swelling of joints in this phase, the patient is relatively symptom-free.

Chronic: Gout attacks may become frequent during this phase and the condition may affect many joints at a time (polyarticular). Tophi formation may also be seen.        

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FINGER CLUBBING -- DIAGNOSIS

SCHAMROTH SIGN 

Absence of a closed triangular space described by the nails of two index 

fingers when their distal phalanges are held in dorsal opposition

PHALANGEAL DEPTH RATIO 

In normal fingers, the distal phalangeal depth should be smaller than the 

interphalangeal depth; this relationship is reversed in the finger with clubbing
.
Since calipers may not be readily available, physicians may estimate the 

phalangeal depth ratio

ANS REVIEW