Download Endo-1-06-99_1-20-99

Endocrinology (1-6-99)
Comp Boards
Adjusting – 20 stations – need to pass 14 of them (70%)
(with at least a 70% at each of these 14 stations)
- Dr. Mannello’s stuff gets added in here
- Net of ~ 24 stations
- Called “Criteria Referenced Grading”
Written – “Norm Referenced Grading” (curved)
- typically, you’re in the bottom 5% of your class if you fail this
- but – possible for no one to fail
x-ray – “Norm Referenced Grading” also
can still go into clinic if you fail the written or the x-ray part (but not both)
but not if you fail the gym part
Dr. Sanders’ E-mail address: [email protected]
Endocrine systems
- all patients have them
- ex – endo  thyroid  Graves’ disease
What do chiros need to know about endocrinology?
- the ability to recognize signs and symptoms and correlate them to etiologies
 clinical reasoning (to reach a Dx from a bunch of patient data)
we do – collection of clinical data
- which tests to do, interpretation
- your clinical knowledge base is important
doctors spend most of their time collecting data and evaluating it
(the actual adjusting doesn’t take very long)
- develop your own style of clinical reasoning and modify it as you go along
hypertension – can miss this in patients if you don’t take their BP
hypoglycemia – a pathophysiologic condition
- you need to take a patient’s blood glucose to see this
symptoms may be the result of hypertension or hypoglycemia (or not!)
find out the symptoms and determine what’s causing them, then do something about them
increased thyroid levels  increased HR (why?)
 increased bowel movements
Cushing’s Disease – increased cortisol level – pituitary problem
Cushing’s Syndrome – increased cortisol level – adrenal problem
- similar symptoms, except some Cushing’s Disease patients are hyperpigmented
(a differentiating feature) (elbows, knees, heels, hands, nose, chin, etc.)
Cushing’s Disease – pituitary tumor  ACTH  adrenal  increased cortisol
Also  increased melanin and melatonin in melanocytes
When ACTH is produced from precursor molecules (PROMC), you also get
melanocyte stimulating hormone and beta___ due to post-translational modification
Course
5-6 quizzes (15-20Q each) (recognition-based)
1st quiz in approximately 2 weeks over Ch. 199 (10 pages)
if miss a quiz, the make-up is fill-in-the-blank or essay (with Dr. Wilkerson)
He prefers that you not take notes in class – listen and pay attention
- all of his slides are on a web site (and in the library – reserved)
(can download and print them)
Endocrinology (1-20-99)
Hormones: distinct chemical messengers that transmit information from one cell to
another to coordinate homeostatic adaptations, growth, development, and
reproduction
endocrine system:
used to talk in terms of a signal
used to believe problems were due to either too much or too little
hormone (problem – this model doesn’t work on everyone)
diabetes mellitus – some people have too much insulin
diabetes insipidus – some people have too much ADH
hormones = effectors that bring about the effect
Q – what causes decreased hormone levels?
Hormones act in distinct locations
But – some other biologically active substances do this also
Hormone receptors are also important
If they are not there, the hormone can’t work
Not related to the endocrine system
Made by protein synthesis, so protein synthesis problems can affect the endocrine
system
hormone – from the Greek word meaning “excite” or “set in motion”.
1 hormone can have multiple actions (ex – testosterone)
1 action can have several hormones (ex – glucose metabolism)
testosterone – males have more red blood cells than females
due to increased synthesis of erythropoietin
Different actions are due not to different mechanisms but to differences in target cell
response.
Glucose Maintenance
Insulin – protects against hyperglycemia via hepatic glucose production and enhanced
glucose uptake
glucagon – primary – protects against hypoglycemia
}
stimulate
epinephrine – backup - protects against hypoglycemia
}
glucose
norepinephrine – backup - protects against hypoglycemia }
production
cortisol – backup - protects against hypoglycemia
}
(in liver)
thyroxine – stimulates appetite
There is a wide range of interaction of hormones.
Peptide Hormones vs. Steroid Hormones
Differ in structure and mode of action (how they do what they do)
Ex – shot in the head = manner of death
Mode of death = hypoxia
Injection in liver:
mode = liver damage
The mode depends on the type of cells being stimulated.
Peptide Hormones
Complex peptides:
Intermediate peptides:
Small peptides:
Dipeptides:
Single amino acids:
Steroid Hormones
Intact steroid nucleus:
Broken steroid nucleus:
LH, HCG
insulin, glucagon
TRH
thyroxine
histamine, serotonin
adrenal hormones
Vitamin D
Last 20 years: learned a lot about the endocrine system
1) Peptide vs. Steroid
Present in small amounts
Didn’t even know they existed before 1965
(technology wasn’t good enough to detect them)
ex:
grams:
mg:
ug:
ng:
pg:
fg:
albumin, hemoglobin
glucose, cholesterol
T4, cortisol, GH
T3
ACTH
endorphins
before 1965, they couldn’t detect anything smaller than 100 ug
(had to use indirect methods to know they were there)
radioimmunoassay:
Rosalind Yallow (Nobel prize for it)
endorphins
human chorionic gonadotrophin is tiny!
2) Hormone activity has to be controlled
Need to know how this is done
Can’t just control the effects by the concentration of the hormone
Transport: Need an intact vascular system or hormones can’t get to where they’re going
Solubility (peptides are water-soluble, steroids are not water-soluble)
Steroids have to be altered by transport proteins to be water-soluble
(also see this with lipids and cholesterol)
Lipid transport:
Uses the protein part of a lipoprotein (the apoprotein)
If not enough transport proteins, there are backup modes of transport
General transport proteins:
Specific transport proteins:
albumin, prealbumin
thyroxine binding globulin
Cortisol binding globulin
To find what’s in serum, separate them
Use electrophoresis to separate proteins (by size and by net charge)
Ex – Bence-Jones protein in urine
Look for a ‘myeloma spike’ (M-spike)
electrophoresis: use an agar gel
put a drop of serum on it and let it dry for a few minutes
put it in an aqueous medium (pH = 8.6)
(the pH of 8.6 gives most proteins a negative charge)
run a current through the gel for X minutes/hours
stain the gel
get different bands at different distances
5 major bands in serum (alpha-1, alpha-2, beta, gamma, ??)
prealbumin goes in the opposite direction from the rest of the bands
prealbumin is an isovariant of albumin (not much different functionally)
preformed antibodies (gamma globulins) help you ward off infections
how to measure the amounts
densitometry – measures the density of the color of the band
shine a light through the band
record the transmission or absorption
get ‘tracings’ (of peaks for the different band wavelengths)
multiple myeloma has an ‘M-spike’ for Bence-Jones proteins
Specific transport proteins are not exclusive in that a specific hormone can also be
transported by a general transport protein.
Feedback relationships
a distinguishing feature of the endocrine system
the classic model is the hypothalamic-pituitary-thyroid axis
interdependence of glands is involved
Feedback relationships (cont)
The hypothalamus releases TRH, which acts on the pituitary, causing it to release
TSH, which acts on the thyroid, causing it to release T3 and T4, which act on the target
cell, the hypothalamus, and the pituitary.
T3 and T4 feed back to the hypothalamus and the pituitary. High levels of T3 and T4
shut off (inhibit) TRH production.
Note: If you inhibit an inhibitor, you get stimulation.
ex – As thyroid hormones decrease (T3 and T4 decrease), there is less
inhibition of the hypothalamus, so the TRH levels increase, and so on.
thyroid hormone – very potent - a 10% increase can cause a very rapid heart rate
but – you generally don’t get much fluctuation in the heart rate even though the
thyroid hormone fluctuates, due to other mechanisms that help control
hormone activity. (It’s not just based on hormone concentration.)
The same treatment won’t work on all Pts since the problem could be in different parts of
the loop/pathway.
ex – pituitary tumor – secondary to increased TSH
thyroid tumor - primary
hypothalamus tumor – tertiary
primary vs. secondary vs. tertiary tumors
they all look the same clinically, they just have different causes
TRH
TSH
TH
A
indeterminate
decreased
increased
primary
B
decreased
increased
increased
secondary
C
greatly increased
greatly increased
increased
tertiary
TRH – primary – indeterminate – the increased TH tends to decrease TRH
but - the decreased TSH tends to increase TRH