Module 5: Endocrine: DM and Acromegaly Flashcards
Starting off with endocrine pathology is DM, which is the most common endocrine disorder. First, explain the levels of C-peptide in your body in relation to insulin
Normal levels: exogenous
Elevated levels: insulinoma (pancreas is secreting insulin which breaks down to C-peptide)
Now there are two types of DM, firs being type I DM. What is the etiology for type I?
Viruses: Coxsackie B4, Rubella, Mumps (molecular mimicry – damage to the beta cells)
Autoimmune: HLA DR3 and DR4 — immune response
–note that since this would be an autoimmune condition it can co-exist with other autoimmune conditions like Lupus, RA, Grave’s, Hashimoto’s
What is the presentation for patients with DM type I?
Less than 40 y.o
Skinny (lack insulin – catabolic state)
Fruity Breath
Vomiting (ketones irritate Area Postrema)
Kaussmal’s Breathing (hyperventilation in response to the metabolic acidosis results in respiratory alkalosis)
Drowsy
Coma
What is the histology for type I DM?
Autoimmune damage to the pancreas by T cells
Complete destruction of the islets of Langerhan’s by lymphocytes
–Isletitis
–Increased CD8 lymphocyte
Is insulin needed in type I DM?
Need insulin for life
What are the acute complications for type I DM?
- Insulin overdose leading to hypoglycemia (most common): confusion, sweating, coma and seizures
- Diabetic Ketoacidosis:
- –trigger is infection (pneumonia, UTI, etc) the body’s response to stress is increased cortisol but cortisol is gluconeogenic so your antagonizing insulin but favoring gluconeogenesis which worsens the hyperglycemia
- -severe hyperglycemia leads to osmotic diuresis and gross dehydration
- –ketone bodies (made by the liver and muscle cells) = acetoacidic, B-hydroxybutyrate - Mucomycosis is the fungal infection that loves glucose so therefore associated with DKA
Now for type II DM, what is the etiology?
- Obese: Increases production of insulin antagonists such as fatty acids and TNF by adipose tissue, esp in central obesity.
- Over 40 y.o
- Associated with PCOS
- More genetic predisposition than type I
- Primary Beta cell defect (genetic) + peripheral insulin resistance (obesity) — hyperglycemia — beta cell exhaustion – type II DM
- NO HLA associated
What is the histology for patients with Type II DM?
Localized amyloidosis
–amylin associated amyloid (AA)
-extra-cellular, hyaline, amorphous
(other endocrine disorder thaw is localized amyloid is medullary carcinoma of the thyroid)
At what point in time do patients with DM type II need insulin?
When the pancreas becomes burned out then the production of insulin will stop
–at this point patients at risk for developing DM
What are symptoms associated with type II DM?
Can be asymptomatic: --incidentally picked up on blood tests Three P's: Polyphagia (only one you dont see in DI) --increased appetite Polyuria: increased urination Polydypsia: increased thirst
What are the acute complications for type II DM?
- Hyperosmolar, non-ketotic coma (aka dehydration + hyperglycemia)
–glucose in the urine — water and Na follows —- dehydration and hyponatremia (leads to cerebral edema – comatose)
Elderly ppl who forget to drink who have DM
For both type I and type II DM, what investigations can be done?
- 2 samples of fasting BG greater than 126mg/dl (hyperglycemia)(better for screening)
- Random Blood Glucose greater than 200mg/dl but with symptoms (polyphagia, polydipsia and polyuria)
- HbA1c greater than 6.5% is diagnostic but more useful for evaluation of long term glycemic control. (over the past 120 days)
- 2 hour plasma glucose greater than 200mg/dl during OGTT (overnight fast + 75mg glucose) – this tests the residual capacity of pancreas challenging the pancreas to produce insulin.
Now for both type I and type II DM what would be the most common causes of death?
Silent MIs (most common) -- silent due to the neuropathy Renal Failure (2nd most common)
Now lets talk about the chronic complications of both types of DM. First lets talk about the Macroangiopathy complications. What is the major complications?
Atherosclerosis in large to medium arteries
Risk Factors: hyperlipidemia, smoking and HTN
–Atherosclerosis — rupture of atherosclerotic plaque — superimposed thrombus —- narrowing of lumen – ischemia and infarction
–circle of willis = stroke
—coronary blood vessels = transmural MI (painless due to autonomic neuropathy) = most common cause of death
–Peripheral vascular disease: intermittent claudication followed by pain at rest –ulcers and gangrene
–Renal Artery Stenosis: HTN due to JG cells secreting renin in response to hypoperfusion
Moving onto Microangiopathy complications of diabetes the first is neuropathy. What is the etiology for this?
Affects the capillaries, arterioles and small blood vessels
Etiology: glucose – sorbital via aldose reductase – sorbital accumulation
Neuropathy is first because nerves dont require insulin for sugar uptake
What is the first type of neuropathy seen in patients with DM type I and type II?
Distal Symmetric Peripheral Neuropathy: glove and stocking distribution
—mostly sensory but can affect motor nerves (muscle weakness and atrophy)
What are the other neuropathy signs seen in patients with type I and II DM?
Mononeuritis:
–loss of just radial nerve = wrist and foot drop
Autonomics:
–sexual dysfunction: impotence
—diabetic gastroparesis: loss of stomach stretch receptors and decreased motility = early satiety, bloating and constipation
–neurogenic bladder due to loss of PNS – stasis –UTI – ascending infection to kidney — acute pyelonephritis
–silent MI because no peripheral pain sensation
–wrist and foot drop = loss of radial nerve
Cranial Nerves:
–3,6,7 primarily
–late complication
Explain the diabetic foot in regards to Neuropathy in type I and II DM?
Diabetic foot: ischemia + neruopathy + infection
- -recurrent infections that can’t heal properly due to available glucose for bacteria.
- -also seen in patients with Cushing’s Disease b/c cortisol antagonizes insulin — hyperglycemia — type 2 diabetes
The next microangiopathy chronic complication is Retinopathy in type I and II DM. What is the etiology for this?
Etiology: Glycosylation of proteins — advanced glycosylation end products (AGE)
–loss of pericytes earliest structural change (Don’t see nuclei surrounding vasculature): maintain the structural framework
There is pre-proliferative and proliferative retinopathy. What is seen in pre-proliferative retinopathy?
Microaneurysm’s due to loss of pericytes
- -rupture of microaneurysms — dot and blot retinal hemorrhages, hard exudates, and cotton wool spots (Due to ischemia – retinal infarct)
- -cotton wool spots are also seen in HTN retinopathy
What is seen in proliferative retinopathy?
Neovascularization (due to VEGF) without pericytes – hemorrhage – retinal detachment and blindness
–point in which you would consider doing laser surgery in a patient
What are other retinal chronic complications in type I and type II DM patients?
Glucoma
Cataracts: due to sorbitol accumulation
-nerves and lens dont need glucose for uptake
–glucose taken up into lens without insulin – reduced sorbitol via aldose reductase – attracts H20 — cloudy lens/cataracts
The last microangiopathy complication in type I and type II DM is nephropathy. Which involves what?
Athersclerosis of renal artery
- -papillary necrosis due to ischemia of renal papillae – coagulative necrosis and atrophy of kidney — increased susceptibility for infections (Recurrent acute pyelonephritis)
- -autonomic neuropathy also increased susceptibility to infections due to loss of PNS and ability to empty bladder
- -atrophy tubules — fibrosis — chronic renal failure
What casts are found in nephropathy of type I and type II DM?
Lipid: nephrotic Granular (muddy brown): tubular necrosis WBC casts: pyleonephritis Waxy: kidney failure Hyaline: dehydration
