Endocrine disorders and diabetes Flashcards
what are the basic problems of endocrine disorders
- hypersecretion (inc hormone (H) production)
- hyposecretion (dec or no H production)
these result in inappropriate target cell responses
where are hormones sites of actions. how are they specific?
their sites of action arent where theyre released
they have specific target cells with surface receptors for the H. when the H binds it acts
etiology of hypofunction
-in order to synthesize hormones you need reactants and enzymes. eg to make thyroid hormones you need iodine
- dietary deficiency
- metabolic defect (eg missing enzyme)
- receptor defect
- immune disorder (eg T cells causing damage)
- no trophic stimulation->atrophy (we need trophic stimulation for H release)
- Tx for hypersecretion
etiology of hyperfunction
- inc trophic stimulation (negative feedback control is nec for H balance)
- defect in negative feedback
- secretory tumors (this could occur with a tumor which may initially resemble the tissue of origin. In the early stages of dev it might secrete something eg a H. This tumor may not always be in the gland, it can be ectopic-located elsewhere)
what is the most common endocrine disease
dm
RISKS FOR diabetes ARE SIMILAR TO the risks for
CVD
is the pancreas more endocrine or exocrine
its 99% exocrine
1%, the islets of langerhans produce hormones
GLUCAGON
is produced by
produced by alpha cells in the islets of langerhans of the pancreas released when blood glucose is low
insulin
is produced by
action
produced by the beta cells in the islets of langerhans of the pancreas released when blood glucose is high
third hormone produced by the pancreas
is it only produced in the pancreas
somatostatin
it is produced elsewhere in GI system and nervous system
DM is a disorder of…
insulin action or secretion which causes widespread metb problems with proteins, carbohydrates and lipids
action of glucagon
It stimulates the conversion of stored glycogen (stored in the liver) to glucose which can be released into the bloodstream. This process is called glycogenolysis.
It promotes the production of glucose from amino acid molecules. This process is called gluconeogenesis. It reduces glucose consumption by the liver so that as much glucose as possible can be secreted into the bloodstream to maintain blood glucose levels.
Glucagon also acts on adipose tissue to stimulate the breakdown of fat stores into the bloodstream.
action of insulin
action: gives ability to metabolize carbohydrates, fats, and proteins to store glucose in the liver and to convert glycogen to fat stores. Inhibits the production of glucose by the liver
function of somatostatin. how is it controlled?
inhibits the secretion of growth hormone, TSH, glucagon, and insulin.
it also dec GI motility and secretion
negative feedback with the hormones it inhibits
what is diabetes mellitus
a disorder of insulin action or secretion which causes widespread metb problems with CHO, proteins, lipids
it is an absolute or relative insulin deficiency that leads to compromized glucose homeostasis
what occurs with absolute deficiency of insulin vs reltive
the beta cells are damaged in absolute.
in relative deficiency the beta cells are intact but there is a problem at the target cell level
which body systems are most affected by complications that can arise form DM
how serious are these complications
CV, ocular, renal, neuro
both the acute and chronic complic are life-threatening if uncontrolled
how is DM classified
which is most common
how is type 1 further broken down
into Type 1 (10%) and Type 2 (90%)
others such as gestational, drug induced…
Type 1A is immune based (90-95% of cases). the remaining 5-10% are 1B and idiopathic
etiology of DM in general
complex trait (polygenic and environmental factors
etiology of Type 1 DM
- familial (10x inc risk)
- “insulin gene” on Chr 11 (10% of those w type 1 have this) the insulin gene codes for proteins that regulate the fx of Beta cells
- MHC genes on Chr 6 (40%) causes self targeting
what is Type 2 in young people called.
what is wrong with this term?
MODY-mature onset diabetes in the young
it is contradictory
in the past when there wasnt access to so much junk food Type 2 Dm occurred in the 40s+ but is now occurring early d/t poor lifestyle, inacitivy etc
etiology Type 2 DM
etiology isnt clear cut
50% is d/t glucokinase gene on Chr 7
once glucose enters the cell its phosphorylated to keep it inside the cell for metabolism. Glucokinase is the enzyme that phosphorylates it.
for people with Type 2 Dm the glucose wont stay in their cell and they cant metb it so they get hyperglycemia
what is prediabetes
what are good measures to show whether someone is prediabetic. Where would the results be
it is a metabolic stage that progresses to diabetes.
impaired fasting glucose (6.16.9mmol/L)
impaired glucose tolerance (7.8-11mmol/L)
HbA1C (6-6.4%)
what is IFG and how would it appear if prediabetic
it is when you have an IFG (impaired fasting glucose) of 6.1-6.9mmol/L which is higher than normal. Normal max should be 5.5.
for this procedure you get the pt to fast (usually overnight). You are putting them into the post-absorptive state.
how would you get an IGT
fast the pt overnight. Before they take in any food/glucose you measure their blood glucose. Their blood glucose will inc after they take in glucose (15min after) The beta cells will release insulin to dec BG. IF this doesnt happen and BG is still high it indicates impaired GT.
what is HBA1C. what is a normal value vs a prediabetic value
1C is a subclass of adult HB which has the highest affinity for glucose. When you have elevated blood glucose the glucose will irreversibly bind to all proteins in the blood such as HbA. When the glucose binds to any protein it makes it dysfunctional.
what is metabolic syndrome
it predisposes pts to Type 2 DM and CVD some features -IFG -IGT -I resistance -HTN -abdominal obesity -hyperlipidemia
abdominal obesity and metabolic syndrome
measures for males that indicate metabolic syndrome
for women
if it is this number what is this called
women >88cm+=diabesity
for men >102cm is diabesity
would someone with type 2 diabetes have metabolic syndrome
most likely yes
type 1 DM usually occurs ____
d/t
is
-usually early age onset
-autoimmune
genetic predisposition
env triger (virus??) not sure which virus
-progressive destruction of beta cells
up to 90% destroyed
absolute insulin def
-Insulin and islet cell autoAB produced
in Type 1 Dm why do autoAB form?
d/t the preceding viral infection
what is insulitis and why would this occur.
if a pt had this what kind of cells might be visible histologically
inflm of the beta cells in the islets of langerhans.
this could occur fromt he autoab that arise i Type 1 DM and whenever you have autoimmunity there are T cells present.
Histologically you would see Tc cells int he Islets of Langerhans
Type 2 DM
beta cells?
what is happening with insulin levels? release? response? etc?
worse than type 1?
-beta cells are mostly intact
-there is a relative insuin def
delayed secretion
defective target cell response
insulin resistance “absence of a hypoglycemic -response during states of hyperglycemia”
-insulin levels can be normal, high or low
-less severe form than Type 1
where there is tissue destr what protein will deposit?
amyloid
in the face of hypoglycemia how does the liver respond
it rel glucose through glycogenolysis
what is a renal threshold
what is it for glucose. what would happen if it were 5mmol/L greater than this
the conc of a compound or solute in blood above which that compound will appear int he urine
10mmol/L
if it were 15mmol/L conc in blood then 5mmol/L would appear in the urine
what are the 3 processes involved in urine formation
filtration
active secretion
reabsorption
how does a hyperglycemic get dehydrated
what might dehydration lead to
glycosuria->inc osmotic pressure in the filtrate->fluid enters filtrate->polyuria->glucose inc conc of solute->draws fluid into urine->dehydration which may lead to polydipsia (excessive thirst and intake)
ketonuria may contribute to the dehydration by pulling more fluid if it is bad enough
patho of diabetes (T1, T2)
- I def->impaired glucose utilization and inc hepatic glucogenesis->hyperglycemia (11-67mmol/L->renal threshold is exceeded->glycosuria->osmotic pressure in filtrate inc ->fluid enters filtrate->polyuria-> dehydration->polydipsia (excess thirst and intake??)
- d/t insulin def there is impaired glucose utilization by cells
-inc in mobilization and use of proteins and lipids ->inc protein and lipid metabolites in blood (eg ketones)
(although the body’s primary source of energy is carbs it will next mobilize lipids then protein and convert them into glucose)
-the accumulation of ketones can lead to ketoacidosis->acidotic coma and death. They can also cause ketonuria which enhances polyuria
what part of diabetes causes hyperlipidemia
when you have hypoglycemia and youre mobilizing lipids and protein for energy
mnfts of DM
- polyuria
- polydipsia
- polyphagia (inc appetite and inc food intake)
- weight loss (calories will be lost through urine. the weight loss is not caused by fluid loss.)
- other complications
acute complications of DM (3)
- hypoglycemia
- diabetic ketoacidosis
- hyperosmolar hyperglycemic state (HHS)
which type of Dm is more likely to experience hypoglycemia
why would this occur
Type 1 d/t: --missed meal --insulin OD --exces activity
can–missed meal
–insulin OD
–excess activity
only cause hypoglycemia in DM pts
no. can also cause DM in nondiabetics
Tx fo hypoglycemia
mild: 15g of CHO carbs p.o.
severe (
hypoglycemic coma
when does it occur
brain deprived of glucose
-LOC is deprived of
Tx of hypoglycemic coma
1mg of glucagon subcu or IM
DKA 42-11
diagram
if you encounter a diabetic in coma what do
dont know if hyper or hypoglycemic
what is nec for DKA to occur
either a severe def of I or
excess glucagon
what are the derangements from DKA
- hyperglycemia
- ketosis
- metabolic acidosis
all of this will cause hyperglycemia. the cells cant use glucose so they use lipids which forms glycerol and is converted to glucose in liver (gluconeogenesis). the glucose enters blood but body still cant use it
it ends in circultory shock (if the fluid loss is extreme enough i assume?)
HHS=
occurs more often in
is d/t
what happens
hyperosmolar hyperglycemic state
usually in T2 and elderly
d/t CHO intake and inc insulin resistance
severe hyperglycemia->hyperosmolarity->cellular fluid efflux->glycosuria->water loss->dehydration
there is no ketoacidosis
why is there no ketoacidosis in HHS
lipolysis causes ketoacidosis. there is generally not a total I def as it affects usually Tpe 2 Dm
still dont really understand this
chronic compilcations occur approx ___yrs after disease onset
15
chronic complications of DM
vascular damage->atherosclerosis, MI, CVA ..retinopthy ..retinopathy ..neuropathy ..infections
all the ones with dots above are underpinned by changes in the vessels
CAD
CVA
which would also be caused by vessel changes and werent n his list for some reason
what type of infections happen w DM pt
what prevalence do infections have
45% prevalence
foot infections and UTIs are most common
how do metabolites in vessels cause damage
when theres hyperglycemia the glucose binds to proteins in the circulation eg albumin, Hb once bound (glycosated proteins) their fx is impaired
all byproducts, glycosylate proteins and products ill bind to endothelium. When removed or bound they cause injury which leads to inflm-> thickening. This affects transcapillary exchange
what is a glucose + a protein
glycosylated protein
if there is impaired transcap exchange what happens to the blood
blood gets more viscous and platelets will agglutinate->impeded blood flow->impaire delivery of resources and removal of wastes. This is a local and systemic problem
process of vascular damage d/t Dm
-metb is altered-> abn metabolites accum and inflict damage
-glucose + proteins-> glycosylated proteins-> nonfx
eg Hb, albumin, collagen, retinal proteins
-glycosylated proteins deposit on endothelium->impaired capillary exchange
-platelet aggregation->blood flow impeded
-impaired healing WHY d/t impaired perfusion, lack of resources and failure of adequate removal of wates
-growth of anaerobic bacteria WHY
why is there growth of anaerobic bacteria w vascular damage in DM
at a tissue level eg peripheral superficial tissue level such as between the toes there is an anaerobic, hypoxic environment. There is a dec of oxygen and buildup of C02, metabolites, not enough nutrients there which allows the bact to colonize
retinopathy as complic of DM
the capillary is damaged-> aneurysms->rupture->visual impairment
-cataracts and glaucoma (dev more quickly in DM)
what are cataracts
how does Dm cause it
the lens is normally transparent but w cataracts the lens becomes opaque->light cant pass through as easlly. Cataracts are part of the normal aging process. It is common to replace lens.
when there is an excess of glucose it will become sorbitol which is implicated in cataracts. There is also an intermed product fructose
what is glaucoma
inc intraocular pressure. It is damage to the optic nerve caused by the inc pressure. of the fluid in eyes eg vitreous humour.
It is not r/t BP
it is assoc w aging but not as common as cataracts
nephropathy and Dm
glomerular damage-> dec! renal fx-> renal failure
Neuropathy
- neural ischemia
- some demyelination (d/t ischemia and inflm)
- poor conduction
this results in diabetics not sensing pain etc
HTN and DM
40% prevalence in DM pts
- it is both a comlication and risk factor for DM
- it is a major risk for MI, CVA, nephropathy
the damage to the capillaries also happens in large vessels which is like atherosclerosis
how would Dm cause MI or CAD
hyperlipidemia (d/t altered metb)-> atherosclerosis-> MI
how does DM put pt at risk of CVA
hyperlipidemia (d/t altered metb->atherosclerosis->CVA
why are UTIs so common in diabetics
d/t impeded perfusion and
-w hyperglycemia the renal threshold is exceeded which allows glucose etc into urine in bladder and is a good env for bacterial growth
why are infections so diff to manage in Dm pt
-d/t vascular insuff (02, Ab, nutrients)
- leukocytes in blood have surface proteins which the glucose may bind to and cause them to cease fx. it also diff for them to arrive to site
- neuropathies (eg cant feel foot and are unaware of infection)
Dx of Dm
- hx (3 Ps, unexplained wt loss
- random glucose >11mmol/L (which isnt ideal as they could have starved, just eaten etc) OR
- IFG (greater than or equal to 7mmol/L) OR
- IGT (>11mmol/L) OR
- HbA1C greater than or equal to 6.5%
how long is RBC life cycle
4 months
Tx of Dm if unsure whether pt is T1 or 2 or just prediabetic what do
how do you treat prediabetic
differetiate 1 vs 2 by measuring insulin level
lifestyle modification for type 2 for several months which often works
if lifestyle doesnt work as Tx for DM what next
glycemic control.
oral hypoglycemics (Type 2)
-inc tissue response to insulin
-stimulates beta cels
-dec hepatic glucogenesismetformin is often used on its own after HbA1C of ___
after 2-3 months of lifestyle modification
what would be used for T1
what would be used if HbA1C >9%
7%
T1=insulin
>9% then use metformin and insulin
why not give oral insulin
insulin is a protein which would get broken down into a.a in GI tract
exocrine fx of pancreas
proteases
pancreatic lipase
amylase
other than somatostatin, insulin and glucagon what H does the pancreas prod
Gastrin: This hormone aids digestion by stimulating certain cells in the stomach to produce acid.
vasoactive intestinal peptide
if there are no carbs available what would the body use next as fuel
lipids
-inc in mobilization and use of proteins and lipids ->inc protein and lipid metabolites in blood (eg ketones)
(although the body’s primary source of energy is carbs it will next mobilize lipids then protein and convert them into glucose)
-the accumulation of ketones can lead to ketoacidosis->acidotic coma and death. They can also cause ketonuria which enhances polyuria
what is the insulin gene and what does this affect?
-“insulin gene” on Chr 11 (10% of those w type 1 have an issue with this) the insulin gene codes for proteins that regulate the fx of Beta cells
what gene causes self-targeting in Type 1 DM
MHC genes on Chr 6 (40%) causes self targeting
what is glucokinase?
which type of DM is this assoc with?
how is this assoc w genetics?
what effect does this have on blood glucose?
50% is d/t glucokinase gene on Chr 7
once glucose enters the cell its phosphorylated to keep it inside the cell for metabolism. Glucokinase is the enzyme that phosphorylates it.
for people with Type 2 DM the glucose wont stay in their cell and they cant metb it so they get hyperglycemia
