Friday, April 26, 2013

Integrated endocrinology :Concepts


Integrated endocrinology

We can regard the endocrine system as having the following physiological missions

Regulation of sodium and water balance: preservation of the volume/pressure reservoir required for tissue perfusion

Regulation of calcium balance: preservation of extracellular fluid concentrations required for membrane integrity, intracellular signaling, hemostasis,etc., and preservation of skeletal integrity

Regulation of energy balance: preserving, accessing, and interconverting metabolic fuels to meet
cellular energy demands

Coordination of processes for coping with a hostile environment

Coordination of growth and development

Coordination of processes associated with reproduction and lactation

It is clear that at least some aspect of virtually every physiological system lies within the realm of endocrine control

No single hormone or endocrine gland can accomplish any of these missions alone, and virtually every hormone participates in fulfilling multiple missions
Consequently, it is to understand not only how hormones act but also how they interact.

                Control of hormone action

Negative feedback
The essence of negative feedback control of hormone secretion is that some consequence of secretion blocks or dampens further secretion
 Hypothalamic input to the negative feedback system allows for episodic override and adjustment of the set point in response to environmental inputs

Positive feedback

 In positive feedback systems, the consequences of hormone secretion feed back is to reinforce the drive for secretion rather than dampen it.

Rather than maintaining matters stable and unchanging, positive feedback creates instability and leads to explosive changes . Consequently, positive feedback is rare in biology

Eg: During parturition
      Coagulation
      Generation of action potential

Concepts of  Specificity

Because of “internal secretion” of hormones into the blood, hormones are widely disseminated throughout the body and have access to virtually all cells. However, only certain cells respond to any particular hormone. These “target” cells differ from all other cells in the respect that they express receptors for that hormone.

The information delivered to the target cell is present in the structure and three-dimensional conformation of the hormone and is sufficient only to activate the receptor.

 It appears that activation of one particular receptor is an all-or-none phenomenon, with gradations in response resulting from gradations in the numbers of receptors that are activated in each cell.

 The receptor, by virtue of the biochemical changes it triggers in transducing the signal, initiates a particular biochemical change or group of changes. The signals generated in the target cell are determined by the signal-transducing component of the receptor.



In many cases, there is more than a single class of receptors for a particular hormone, and each class usually activates a different biochemical pathway.


The nature of the final response elicited in a target cell is not determined by the intracellular signal generated by the receptor but, rather, by the effective machinery expressed in the cell as a consequence of its  differentiated state


For example,
Receptors for the parathyroid hormone are present in the basal membranes of cells of both the proximal and distal portions of the nephron . Binding of the hormone initiates the same signaling cascade in both cell types,but the proximal tubules respond by decreasing phosphate reabsorption from the glomerular filtrate and increasing hydroxylation of vitamin D, while the distal cells respond by increasing reabsorption of calcium

CONCEPTS RELATED TO TARGET CELL RESPONSIVENESS

Responsiveness of target cells to stimulation by their hormones is not constant but may vary widely in different physiological states and is often adjusted by the actions of other hormones or local paracrine or autocrine agents as well as the primary hormone

Factors that govern the magnitude of the response to a hormone.

1)  Concentration of the hormone
        which in turn is determined by
a)      The rate of hormone secretion
b)      The rate of delivery by the circulation to the target cell surface, which is slower if the hormone circulates bound to plasma proteins than if it is unbound
c)       The rate at which the hormone is degraded or excreted

2) Number of competent target cells that express functional receptors

3) The sensitivity of each target cell to hormonal stimulation is not constant and depends on

a)      The number of functional receptors that are expressed
b)      The affinity of the receptor for the hormone
c)       The status of postreceptor amplification mechanisms
d)      The status and abundance of effector molecules

The sensitivity to a hormone of target organ is often defined as the concentration needed to produce a half-maximal response




Target organ sensitivity is not constant and is often adjusted in accordance with physiological circumstances.


Can be done by:
a)      Changing the number of receptors expressed.
b)      On the cellular level, upregulation or downregulation of effector molecules such as enzymes, ion channels
c)       On the tissue/organ level aggregate of the contributions of all of the respond-ing cells, so that the magnitude of the response to a particular concentration of hormone is a function of the number of available cells as well as the competence of each cell.




Factors that govern the duration of the response to a hormone.

1)  The duration of hormone availability, which is determined by
a)      The duration of secretion
b)      The rate of hormone clearance from the blood, usually described as its half-life

2)  Whether the response results from
a)      A rapidly reversible covalent change, i.e., phosphorylation or dephosphorylation of key enzyme
b)      Or genomic events involving synthesis of proteins and the half-lives of the proteins


Saturday, April 20, 2013

Fun and interesting facts about thyroid


In Switzerland in the 1880's Theodor Kocher demonstrated that total thyroidectomy caused hypothyroidism but thought initially that the symptoms were due to chronic air way obstruction. Kocher performed over 2000 thyroidectomies. 

He reported his early experience of thyroidectomy for Grave's disease which had at that time a mortality of 13%. Later in in 1883 his mortality for total thyroidectomy for Grave's fell to a remarkable 1%. It was not until 1888 that he realised that the symptoms of total thyroidectomy were due to lack of thyroid.

He then recommended as a treatment for total thyroidectomy "half a sheep's thyroid lightly fried and taken with current jelly once a week". The modern treatment of hypothyroidism was born. Kocher was awarded the Nobel Prize for Medicine in 1909.



The American surgeon William Halsted could trace accounts of only eight operations in which the scalpel was used between 1596 and 1800. During one of these procedures, described by Fabricius in 1646, the patient, a 10‐yr‐old girl, died on the table and the surgeon was gaoled!

Thyroid hormones affect function of virtually every organ system & every tissue in the body

When overactive, everything is turned up – feel hot (increase in metabolism), restless/anxious, hyperactive heart , respiratory rate increase & GI motility, secretion (causing diarrhoea) etc.

When underactive, everything is dialed down
slow, cool, fatigue, constipation etc



Thyroid enlargement (goitre) can be present in hypothyroid, hyperthyroid or euthyroid state


Though T3 is the active form, T4 is the preferred hormone for treatment of hypothyroidism.

Long circulatory half life of T4 provides remarakable stability ensuring a steady supply of t3 once a therapeutic dose is established.

Shorter half life of T3 makes it less appropriate for long term use.
Also there is an additional disadvantage of bypassing regulatory mechanisms controlling T4 to T3

Friday, April 19, 2013

Parathyroid


Hi everyone,

Here goes my another powerpoint in endocrinology series

Parathyroid and calcium homeostasis

Keep reading and remain updated




Soon I will be posting interesting facts about the the topics

Feedback and suggestions invited

Wednesday, April 17, 2013

thyroid powerpoint

hey,

This is my first power point help for students both undergraduate and postgraduates.

All feedback suggestions are invited.

Also if explanation is desired on any subtopics, you can always post a comment, and i would try to elaborate  on that topic to my best possible capacity.

Also u can let me know of any topic, you need the power point of.

so here goes the first power point on Thyroid physiology with some pathological aspects