Vasculitis in diabetics

#KYJ - Vasculitis

Nurse M asks "can you do a blog on vasculitis and why it's a diabetic complication?"

So here we go...

Vessel disease and in particular, vasculitis has recently been found to be associated with fibromyalgia and related Neuralgia (nerve pain).

Literally, vasculitis means inflammation of the blood vessels.  It is just one of a myriad of Autoimmune disorders.

Think of it as rheumatoid arthritis inside blood vessels.   Some medical co-morbidities are often prerequisite. Perhaps the most well known is  Diabetes.

Diabetes is commonly associated with both microvascular (small vessel) and macrovascular  (large vessel) complications. Vessel hardening (sclerosis), endothelial injury from viscous blood, and fatty plaques (atheroma) all contribute to the vessel inflammation that is vasculitis.

Hypertension, frequently present in diabetics, accelerates the onset of vasculitis. Over the past 10-15 years, we have developed a good understanding of the underlying chemical changes in diabetic blood vessels. 

What we know, is that vasculitis is immune, mechanical (BP) and metabolic; and that these factors interact to stimulate the release of cytokines (cell communication proteins) and growth factors in branches of small blood vessels.  Eyes, kidneys, and hands/feet.

In diabetics a common factor is byproducts of glycated proteins in diabetic blood.  You better know of these proteins as HbA1C. The higher their HbA1C is, the more vasculitis and subsequent effects.

Two important substances over secreted in diabetics, is seen in the glomerulus, and the retina vessels. 

In the kidney, "transforming growth factor-beta" has been observed to be prosclerotic (causing hardening) in  renal arterioles.  This fuels and exacerbates the Renin-Angiotensin response which pushes up BP.

In the retina, vascular endothelial growth factor and its receptor, vascular endothelial growth factor R-2 are increased.  Gobbledygook I know, but these cytokines cause new blood vessel growth (angiogenesis). 

Ultimately, the cell changes caused by these cytokines stimulates inflammation- Vasculitis.

Now here is the clincher, inflammation inside blood vessels, traps the smallest cholesterol carrier proteins called LowDensity Lipoproteins (LDLs).  This is in essence, the formation of cholesterol deposits in arteries (atheromas), narrowing and hardening the vessels (atherosclerosis).

DM and cardiovascular disease are inextricably linked.

So the next time the diabetic you are looking after complains of fatigue and flu like aches, it may very well be vasculitis, and is contributing to kidney failure, blindness, small peripheral vascular disease (ulcers and slow healing), and a massive increase in risk of MI and CVA.

Keep those HbA1C levels in check, monitor vision, renal function and manage hypertension aggressively.

#ECT4Health 

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Wee.

Obstructive Sleep Apnoea

Sleep Disorders Week

So I thought I'd do a quick #KYJ on Sleep Apnoea.

This is part 1 of 2.

There are two main types of Sleep Apnoea.  Central Sleep Apnoea (CSA), and 

Obstructive Sleep Apnoea (OSA).  As the name implies, OSA is a condition where soft tissues of the throat relax when sleeping, occluding or obstructing the airway. During periods of apnoea, oxygen levels in the blood fall (often dramatically -SpO2<75%).  While blood CO2 rises slightly, the effect of hypoxaemia is the most profound, and causes most of the acute sequelae. 

Let's just recap normal breathing stimulus.

Normally your brain stimulates you to take your next breath, based on a complex biofeedback mechanism.

When pH of the blood (and CSF) falls - acidosis; this is the primary trigger of breathing. Unlike you were probably taught, high CO2 isn't a direct stimulator of breathing, but it is secondary stimulant due to the fact that high plasma CO2 causes pH to fall (Carbonic or Respiratory Acidosis). So it is true to say high CO2 stimulates breathing, but indirectly through acidosis.

The second and more primitive stimulus to breathe is low plasma oxygen.  You were born with this mechanism, which you probably learned about when you were taught why a new born baby draws that first breath.   It is called "Hypoxic drive", but early in your infancy you switched to the high CO2/low pH trigger.  Called Hypercarbic drive, this mature lung, primary mechanism isn't in play during OSA, because CO2 doesn't dramatically rise.  You are asleep (or trying to), and at rest, you just don't make as much CO2.

So.  The Snorer is left with multiple obstructions, and apnoeas.  This leads to drop in plasma oxygen (hypoxaemia).  When oxygen falls low enough, the secondary hypoxic drive mechanism kicks in waking the snorer. They adjust position and inhale, restoring plasma oxygen levels.   The sleeper then drifts back to sleep with out realising that they woke up, and the whole cycle starts again.

Snoring is almost always present (even diagnostic).

Daytime tiredness morning headaches hunger and weight gain are common.

Poor concentration irritability and its extreme breathlessness on exertion, and ankle swelling which is the hallmark of right heart failure.

In its mildest form, people stop breathing every 5-12mins (5-14 episodes of apnoea/hour)

Moderate OSA is diagnosed at 15-30 Apnoea/hr

And severe OSA >30/hr.

That's an Apnoea every 1-2 mins.

Waking that often, causes the sufferer to feel like they are never well rested.  They may think they sleep all night, but realistically never completed important restorative sleep cycles, and this takes it toll on tissue healing, cell regeneration and hormone levels.

The body, in a constant state of stress, releases massive amounts of cortisol (our natural hydrocortisone) and Adrenaline driving up BP, and heart rate. While cortisol exerts its effects as glucose intolerance, insulin and leptin increase/resistance, obesity, atherosclerosis and T2 Diabetes, the adrenergic stress response contributes to the development of heart failure.

Just let that sink in for a minute.  Your snoring is causing your heart failure obesity and diabetes.

The age-old question of does a obesity cause OSA, or does OSA cause obesity is yet to be completely answered, but there is a biochemical body of evidence to suggest that poor sleep equals neurohormonal changes that lead to altered carbohydrate metabolism, and all the diseases linked to it.

You don't need to snore and snoring is the single most important feature of obstructive sleep apnoea. recognise it early nip it in the bud.   If you are sleeping next to that special someone who snores. Know this- it is not about your sleeplessness, it is about theirs.

Diagnosis :

Sleep studies are done to measure EEG , ECG and oxygen saturation, then when the moon is full a respiratory physician gazes at the cauldron of data and diagnoses OSA.

Treatment 

1. Surgery to remove or cauterise part of the soft palette.
2. Continuous positive airway pressure (CPAP) ,which blows air into the throat to splint the pharynx open. 
3. Jaw manipulation devices that thrust the lower jaw forward in an under-bite, while sleeping.  You remember from airway management courses that jaw thrust pulls tongue off the pharyngeal wall.
4. Tennis ball in a bum-bag.  Stops old mate rolling on his back and occluding his airway.

Big topic that we can't tackle comprehensively in one post.

Tomorrow (in our Sleep Week) we will look at Central Sleep Apnoea (CSA).

Hope you catch some zzzz! 

#ECT4Health 

ECT4Health

Histamine- the why and why

#KYJ - Histamine and Mast cells. (H1)

In a course on Respiratory nursing last week I was asked about the role of Histamine. Specifically H1.  Not the H2 variety in gut.

So here is my analogy:  imagination needed.

Say there was a bad guy (Buggsy Peanuts) outside your house.  To deal with him you needed to get out of your house.

You are too big to fit out the window so but you you don't have a key to get out the door.

You are stuck inside with Basil, your frightened mate.  Buggsy the bad guy is outside.  Picture it?

Ok- your friend Basil, can't deal with the bad guy but does have a door key.   Basil opens the front door for you, and you you go and deal with Buggsy.

Specialised White blood cells called Basophils (Basil) possess a key that opens pores inside blood vessel walls.   That key is a protein called Histamine.

Ordinarily, large allergen or pathogen fighting phagocytes can't get out of the blood vessels to fight allergens or pathogens, so basophils inside blood vessels and Mast Cells in your tissues (mast cells are just basophils outside the blood stream), produce this Histamine key to make blood vessels porous to allow white blood cells out to attack invaders.

Think of histamine as a protein like insulin, but instead  of opening doors for Glucose to move , histamine opens doors for immune fighting cells to migrate to the tissues where the epic battle between Buggsy Peanut and the White knights of the immune system attack.

Now the downside to this histamine, is that its very action of Vasodilation and increased permeability, causes plasma and water attracting proteins (Albumin) to leak into tissues - Oedema is the result.

Engorgement of vessels close to the invasion causes the blood flow to increase giving rise to redness.

Now reflect on the last ant sting or mosquito bite.
It was red, hot , swollen and painful/itchy wasn't it.

Local histamine responses in skin causes these same symptoms.  They are called urticaria or hives, and are typical in allergies.

If histamine response is in the nasal mucosal or sinus tissues, then the swelling and congestion is called Allergic Rhinitis (Hay Fever), or in sinuses-sinusitis.

If the histamine response occurs in upper airway structures like Lips, tongue and throat, it is referred to as Angioneurotic oedema, or simply angiooedema.  This is a common symptom in a life threatening allergic reaction, and often compromises the patient's airway.   You will know it as the deadly symptom in Anaphylaxis.
When the response is in the lungs, and bronchial tissues become swollen then histamine is one player in the diseases of Asthma and Broncheolitis.

The above examples are all local effects
When the histamine release is systemic, the massive overwhelming release of histamine in all vessels, causes such vasodilation and capillary leakage, that the patient loses their circulating blood volume (hypovolaemia) and their distribution of blood between arteries and veins becomes critically imbalanced (maldistribution).   This is a complex and life threatening cause of shock.  In severe allergic response it is called anaphylactic shock, and in severe pathogenic responses, it is called Septic Shock.

Recap:
Anaphylaxis causes anaphylactic shock.
Infection causes septic shock.

Histamine is a potent vasodilator . And makes blood vessels engorge and leak.

Can you now see the role (in mild allergies) of drugs that block or inhibit histamine?  These are a family of Anti-cholinergic drugs called antihistamines.   Examples include Loratidine, Zadine, Clarityne, polaramine, Telfast and some of the older phenothiazine drugs like the Rock Star -Promethazine (Phenergan).

All antihistamines cause sedation but only if the drug can cross the blood-brain-barrier.  Phenergan and Polaramine are examples.

Any how- as usual, I digress.

The point is Basil (Basophils) holds the key (Histamine) to the door (vessel wall) so you (Phagocyte) can get out and kill Buggsy Peanut (pathogen or allergen).

If it was you who asked the histamine question, Thankyou for stimulating such a great topic for our #knowingyourjargon (KYJ) series.

Check out the blog for more. There is heaps of #FOANed

Autoimmune Hepatitis

#KYJ -  AIH -Autoimmune Hepatitis.

AIH is an ideopathic destruction of the liver by the body's own immune system.   In a similar vane to rheumatoid conditions where the immune system attacks joints and other connective tissues, AIH attacks the liver (Hepa*),leaving it inflamed (*itis)= hepatitis.
It is not related to viral hepatitis like HepA, B, C or other viral disease.
It is not related to alcohol use or drug taking like Cirrhosis of the Liver.
AIH has no known cause.  We just don't know why an otherwise normal immune system should turn on one of its own organs (the liver) and seek to destroy it.  That's what ideopathic means; "cause unknown".

All tissue that becomes injured, need to be repaired.  The repair process is called inflammation.  When injured, and subsequently inflamed, the tissues/organs that they form, stop doing the job they were built to do.
In encephalitis brain stops functioning
In arthritis, joints stop working.
In gastroenteritis the gut stops working.
Well as you probably guessed, in hepatitis, the liver ceases to function.

In hepatitis important enzymes and proteins can't be made.
The Liver converts brain damaging ammonia into a less toxic waste, preventing brain injury.
The Liver makes the blood proteins used for coagulation, with out these, bleeding occurs and clotting mechanisms in the body fail.
The Liver manufactures an important blood protein called Albumin which acts as a water magnet that stops your capillaries leaking into your body tissues (Oedema or swelling).
The Liver processes dead red blood cells (bilirubin) and converts this into bile for digestion.
The Liver makes cholesterol which is the building material for all cells in the body.  Without it the body can't repair or make hormones and bile.

Now if inflamed, the Liver can't do these jobs.  Hepatitis leaves toxic buildup of ammonia causing confusion and brain damage.
A toxic buildup of bilirubin stains the skin yellow (jaundice) and causes the hepatitis patient an incessant itch (Pruritus).
The hepatitis patient can't clot, and with less albumin, they develop swollen legs, and swollen abdomens (called ascites).  Occasionally the capillaries in the lungs will leak causing lungs to fill with fluid, breathlessness and reduction of oxygen delivery to all cells.

Hepatitis is a dangerous disease state, and when destroyed, the Liver can't regenerate fast enough to support life. The end stage treatment for AIH is transplant.  The gift of life allows restoration of function to a person with liver destruction.

I hope that this short KYJ on AIH and hepatitis was interesting, and helped you understand this rare liver condition.

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Lizard spit for Diabetes

#KYJ- Incretin -GLP-1
The Gila Monster is a lizard that packs a nasty bite.  It is a rare find in the animal world, this lizard is one of very very few lizards who are venomous.  It's saliva harbours a potent neurotoxin similar to that of Coral sea snakes, but unlike snakes, it's venom glands are in the bottom jaw so it must chew its prey to envenomate.   Of intense interest to the medical community, this saliva also contains a protein from which the Diabetic drug Exenatide is made.

Marketed under the trade name Byetta, exenatide is classified as a GLP1 mimic.
...
Feel informed yet?   No me either.  Read on.

We used to believe that you ate food, your blood sugar rose, this stimulated insulin to be released, and the blood sugar dropped.  Our concept was that the stimulus for insulin release was sugar..... nope.  This simplified cause and effect is not quite correct.
An important stimulant is the act of eating, chewing, smelling or even thinking about yummy food.
Yep.... just thinking about dinner tonight causes insulin secretion.
So this mechanism is fuelled by a protein hormone called glucagon like protein 1 (GLP1, or Incretin).

Incretin is released when eatingsmelling ir thinking about food.  As incretin is secreted this has two major effects, it instructs pancreas beta cells to make insulin, and inhibits alpha cells from making glucagon.
It also prepares cells to be sensitive to insulin.

A newer approach to T2DM management is administering drugs that inhibit Incretin degradation (Gliptins) or mimic the effects of natural Incretin -   This is where Byetta (Exenatide-manufactured from lizard spit) comes into play.  Exenatide is a GLP1 mimic.

Like insulin, Byetta is a subcutaneous injection given daily to weekly.  It's not new (2005) just not as popular as the gliptin drugs, but interesting none the less. #ToxSeries #ECT4Health
...  bite size chunks of pharmacology education.
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GHB street drug

19 Feb 2017
GHB
Overnight in Melbourne more than 30 people were taken to emergency department suffering effects of GHB intoxication.  In this post we refresh what this recreational drug is and look at its effects.

Gamma-hydroxybutyrate, (GHB) is naturally occurring neurotransmitter.  It is the precursor to GABA in our brain and has many functions.  Principally, it is used as a central nervous system (CNS) depressant .
In the 70s and 80s GHB was synthetically manufactured and used as a pharmaceutical to induce sleep and sedation and to provide peri operative pain relief in painful procedures.  It was a complete disaster.
Today, isn't used clinically; it was found, to be ineffective as an analgesic and dangerous.  Dosing proved to be unpredictable and with  high incidence of seizure, unconsciousness and hyperemesis, you have the perfect storm.  Vomiting , seizure and ALOC is a recipe for litigation and coronial inquests.

GHB did not disappear, however, and instead has become popular in the black market.  Athletes began taking supplements laced with GHB due to its ability to stimulate human growth hormone, a hormone known to increase muscle mass and reduce body fat.

Where it really gained popularity was the nightclub, rave party and sleazy date rape scene of the 1990s.  Like some benzodiazepines and alcohol, GHB was used for its euphoric and sedative effects.  Dangerously synergistic with these drugs, it is also commonly combined with Meth (Ice) or its cousin MDMA (Ecstasy) to prolong and enhance the effects of both.

Due to its tasteless, odourless and potent property to produce unconsciousness and disinhibition, the sinister use of GHB slipped into drinks facilitated its use as a date rape drug.

GHB is unpredictable.  Profound unconsciousness with fitting and vomiting , is a massive airway risk, and when paramedics arrived to more than 30 people all affected, it must have stretched resources of the prehospital crews and the local EDs.

From ingestion to symptom onset is between 15 and 20 minutes.  Effects last 1 to 6 hours.  When used along with other intoxicating substances, such as alcohol and methamphetamine, the effects are unpredictable and longer lived.  This makes recreational doses difficult to gauge.  In its cleanest and pure state, safe doses between 1-2 grams, produce serum concentrations between 80 and 100mg/L.
 On the street there is no way for users to tell what dose they are getting when they get GHB illegally.
Common signs of GHB use and intoxication include:
Relaxation / drowsiness
Euphoria, high
Lowered inhibitions
Dizziness/ ataxic /uncoordinated
Confusion loss of time line
Memory loss / amnesia
Nausea vomiting
Slurred speech.
Hallucinations.

When daily users of GHB are stopped abruptly. Discontinuation or withdrawal symptoms can begin in 12- 24 hours and last as long as 3 weeks.  They mimic alcohol or antidepressant withdrawal syndromes.  Common signs of GHB withdrawal include:
Fever
Extreme fatigue.
Anxiety / mood swings
Paranoia, hallucination (like Delirium tremens)
Insomnia and vivid dreams
Tremors
Confusion, irritation, aggitation.

In OD the margin separating a tolerable amount of drug and a potentially fatal dose is very low.  Accidental overdose is very common.

Expect
Vomiting with unconsciousness
Loss of a gag reflex.
Seizures
Double incontinence
Shaking, tremors,
Sternal rubs (not that they are acceptable) are less effective because GHB causes absence of pain response, even in conscious patients).
Nystagmus (rapid side-to-side eye movements)
Bradypnoea
Profuse sweating but hypothermic (T>35)

Treatment of OD
What kills these patients is airway and breathing compromise.  A secondary issue is electrolyte imbalance.
Priority is ABCD.
Airway secured, vent if needed.
Antiemetics, NG tube.
Fluids and watch gases and electrolytes
Supportive care.
#ECT4Health
Hope you enjoyed the timely read on GHB.

Seizure versus convulsion

#KYJ. Seizure vs convulsion

Seizure - that is the chaotic electrical discharge .  It is in the brain. It is a cerebral event.

Convulsion - that is the motor movement, the shaking/ thrashing , Tonic/clonic jerking, commonly called fitting.

Convulsions are often violent movements of big muscle groups caused by the seizure ( they are not one in the same )

Seizures may not manifest in convulsions.  Some experience an absence of alertness or sensory perceptive phenomena like déjà vu, that sense that you've seen or heard the scene before.
Some seizures also manifest in a sensory perceptive phenomena like déjà vu, that sense that you've seen or heard the scene before.
...
No ... my bad!
...
The phenomena called Jamais vu explained as when a person momentarily does not recognize a word, person, or place that they already know.  Is commonly seen in epilepsy a major cause of seizures.

Even day dreaming has been described as a form of seizure activity.

So when a convulsion is the manifestation of seizure activity it becomes a safety issue - especially during the often violent Tonic (muscle tensing) clonic (muscle jerking) phases.  Head trauma, falls and contacting sharp furniture edges during convulsions is a real risk.
If it should be taken to provide some sort of protection particularly from banging heads on solid firm services like the floor.
Contrary to popular believe airway management is not necessary during a convulsion but the moment that the convulsion stops and the characteristic jerking ceases, Standard protocol is that the patient should be safely rolled onto this site and airway maintained.

Final note:  The term status epilepticus is defined as a convulsion that lasts for more than five minutes or more than one convulsion inside five minutes.  Status epilepticus is defined by  convulsion activity and can exist in patients in the absence of a diagnosis of epilepsy.  One of the commonest manifestations of status epilepticus is drug overdose.

Drug therapy of choice if convulsions last longer than five minutes is the Deslan often given intravenously up to 5 mg
Oh
Did I mention the déjà vu.
...
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