endocrine- pancreatic disorder: diabetes Flashcards
diabetes is the most common
endocrine disorder
normally what do beta and alpha cells do in the pancreas?
beta cells produce insulin
alpha cells produce glucagon
where are the beta cells
islet of langerhans in the pancreas
in diabetes there is hypoactivity of?
insulin
-either SECRETION or ACTION of insulin is defective
absolute deficiency of insulin-
absent insulin or very little
relative defiency of insulin-
insulin present but not effective
type 1 diabetes?
approx 10%
absolute insulin deficiency
BETA CELLS are DAMAGED by autoimmunity or ABSENT
type 1A
- immune mediated (90-95%)
- autoimmune destruction of beta cells
type 1B
not autoimmune (5-10%) -idiopathic destruction of beta cells
LADA=
latent autoimmune diabetes of the adult
-type 1 developing gradually and appearing later in life
type 2 diabetes?
less severe, beta cells can still produce insulin, receptors do not respond to insulin
MODY=
maturity onset diabetes in the young- type 2 diabetes developing early in life d/t poor lifestyle
gestational diabetes=
hyperglycaemia during pregnancy, normal after
drug-induced diabetes?
example, from steroids
etiology of t1 and t2?
complex trait- polygenic, multiple defective genes and environmental factors
etiology of t1?
- MHC genes on chromosome 6 (40% have defective MHC genes)
- code for proteins that sit on the surface of cells to show them pathogens (so defence cells can recognize)
- MHC bind to peptide fragments of pathogens and display them on the cell surface for recognition of T cells
- MHC II on antigen presenting cells (such as DC, B cells, macrophages) presents extracellular peptides
- MHC I holds self-antigens identifying the cell (presents intracellular peptides
- some viruses reduce amount of MHC 1, so they can hide from defence cells and not be detected as foreign, NK cells destroy all cells with reduced MHC 1 in response
- OR insulin gene on chromosome 11 (10%have defective insulin gene)—> codes for a protein that regulates division and function of beta cells, impacts insulin production
- OR t cell hypersensitivity to beta cell antigen
- FAMILIAL risk as well!! 10x morelikely
etiology of T2 diabetes
- strong unclear genetic component
- MODY
in MODY 50% of cases it is… which gene
glucokinase gene on chr 7 that is affected
- codes for protein (glucokinase enzyme)
- glucose + phosphate is said to be phosphorylated, which allows glucose to be converted into glycogen and stored
- phosphorylation is brought on by glucokinase, but if gene coding this liver enzyme is defective—> glucose will be taken in by insulin but go right back into bloodstream
prediabetes tests/signs?
- impaired fasting glucose
- glucose tolerance test
- impaired HbA1c
impaired fasting glucose-prediabetes?
6.1-6.9 mmol/L
-overnight fast, BG feasured
normal is 3.5-5.5
Glucose tolerance test?
2 hour oral glucose tolerance test (ingest glucose and monitor plasma levels for 2 hours) if it does not return to normal (7.8-11mmol/l) after 2h pt has prediabetes
-if they have above 11: diabetes
impaired HbA1c?
-6-6.4% is prediabetes
A1c is a subclass of Hba (adult hemoglobin)
-measure of glucose binding to hemoglobin, more will bind if higher levels of glucose
metabolic syndrome effect on diabetes? features?
- predisposes individual to CV disease and type 2 diabetes
- 70% of ppl w it have type 2
- features: abdominal obesity, htn, hyperlipidemia, IFG, IGT, insulin resistance
type 1 diabetes features
early age onset (except in LADA)
- progressive autoimmune destruction of beta cells (up to 90%)
- absolute insulin deficiency—> target beta cell antigens
- islet cell autoantibody production—-> target islets of langerhans antigens, not just beta cells
- Insulitis: swollen, edematous islets of langerhans due to infiltration of T cells, destroying B cells
type 2 diabetes features
usually adult onset
- beta cells intact (number not diminished NO autoimmunity)
- RELATIVE insulin deficiency= either not being produced at right time, not enough or not effective at target cells
3 situations with insulin resistance in type 2
delayed secretion of insulin
defective target cell response
hepatic glucogenesis: formation of glucose (breakdown of glycogen in liver because glucose is not effective at the site the cells are deprrived of glucose, liver releases more glucose (furthering hyperglycemia)
insulin levels in t2 can be
normal, decreased OR increased
-so, insulin levels cannot diagnose t2 as they can in t1
type 2 dm results from
altered genes (such as glucokinase genes). inability to phosphorylate glucose—>liver cannot store it. more glucose circulates causing hyperglycemia
PATHO of both type 1 and type 2 diabetes
both types include some type of insulin deficiency
insulin deficiency —-> impaired glucose utilization and hepatic glucogenesis —-> hyperglycemia (11-67mmol/l)—> renal threshold of glucose exceeded—-> glucosuria —–> increased osmotic pressure in filtrate —-> fluid enters filtrate —-> polyuria —-> dehydration —–> polydipsia
glucose is filtered in the glomerulus of kidney… excess cluose is filtered out into urine which…
increases osmotic pressure of the filtrate, so now fluid is being pulled in, increasing volume of filtrate (polyuria), usually no glucose in urine (should be reabsorbed)
- problem lies in the fact the body has only so much glucose carriers
- if amt of glucose exceeds the quantities of these carriers, it must be excreted
impaired glucose utilization by cells—–>
increased mobilization and use of proteins and lipids as fuel source —–> increased lipid and protein metabolites in blood (ex ketones)—-> accumulation of ketones—-> filtered by glomerulus and enter urine—-> ketonuria —–> increased polyuria
how are ketones produced
by liver from breaking down fatty acids
accumulation of ketones=
decreased pH—-> ketoacidosis can lead to coma and death
onset of type 1 vs type 2?
abrupt onset for t1, insidious for t2
manifestations (signs and symptoms) of hyperglycemia (3 Ps)
- polyuria (and frequency) increased voiding and amt
- polydipsia (excessive thirst d/t decreased fluid
- polyphagia (increased appetite), glucose is not being used by the cells so individual feels hungry
weight loss occurs in? 2 reasons
type 1 diabetes because 1. calories are being lost in urine, and 2. glucose is not being stored as lipids, lipids and proteins are being utilized for energy
obesity is seen in?
type 2 diabetes usually due to environmental factors
acute complications of diabetes? 3
- hypoglycemia
- diabetic ketoacidosis
- hyperosmolar hyperglycemic state
hypoglycemia as a acute complication?
- more freq in type 1 because of insulin injections
occurs if:
-receives too much insulin
-pt does not eat enough food (lack of CHO)
-pt overexerts themselves
-neurons rely on glucose for energy—> cerebral function and activation of ANS will be altered without can lead to coma
treatment of hypoglycemia?
15g (20g- less than 2.8) of CHF PO if conscious
hypoglycemic coma?
d/t inadequate glucose supply to neurons
treatment: glucagon breaks down glycogen and releases gluose
- administer Img glucagon SC or IM
- 50% glucose IV 20-50ml
diabetic ketoacidosis as an acute complication?
usually in type 1 diabetes, biproduct of lipid metabolism is ketones
in type 1 body isnt producing enough insulin which usually helps glucose enter cells to be used as fuel, body breaks down fatty acid
3 requirements (problems) of diabetic ketoacidosis
- hyperglycemia: insulin deficiency and glucagon in excess- insulin not assisting glucose in entering cells, lipids and proteins broken down
- ketosis (formation of ketones): mobilization of free fatty acids from triglyceride sources in adipose tissue leads to increased ketone production and acidosis
- metabolic acidosis
hyperosmolar hyperglycemic state as a acute complication?
- usually in t2 and eldery, can occur from other causes too (like severe infection)
- stateof hyperglycemia and hyperosmolar (concentration of glucose)
- caused by: excessive CHO intake, increased insulin resistance
- hyperosmolarity and dehydration
- NO KETOACIDOSIS: insulin is present so lipolysis does NOT occur!!! no excess of ketones
in severe hyperglycemia—-> hyperosmolarity then….
cellular efflux (glucose flows out of blood and into filtrate causing increased OP in filtrate, pulling in more fluid—> polyuria and glucosuria—> fluid loss and dehydration
chronic complications of diabetes?
cannot be reversed, will continue to persist, gradual onset
-cannot prevent, but can be delayed
ROOT of all chronic complications=
metabolic changes (breakdown of protein and lipid d/t inability to use glucose for energy—-> VASCULAR DAMGE)
vascular damage occurs the same way in both micro and macrovascular… explain:
- altered metabolism= mobilized proteins and lipids—> byproducts—> hyperlipidemia
- glucose +proteins= glycosylated proteins, excess glucose more binding to proteins, makes a large molcule that impacts the function of proteins (decreased) causes inflammation and oxidative damage (free radical formation)
- poor healing d/t damaged vessels= harder to deliver defence cells and oxygen, remove waste
- proliferation of anaerobic bacteria (lots of hypoxic sites due to decreased perfusion… these bacteria thrive here so more infection!!!, especially in feet
microvascular problems? (3)
- retinopathy
- nephropathy
- neuropathy
retinopathy explained
capillary damage with retina—> aneurysms—> rupture —> visual impairment
cataracts—> lens should be transparent, buti n cataracts the lens are clouded, impairs vision. occurs with age but faster in DM. glucose–> sorbitol which accumulates and is difficult to remove= cloudy!
glaucoma—> damage to optic nerve d/t increased intraocular pressure from buildup of fluid in eye
nephropathy explained
glomerular damage–> decreased renal function –> failure
neuropathy explained
damage to neurons
- neural ischemia (not enough o2)
- demyelination of neurons –> neural deficit or poor conduction—> impaired sensation
macrovascular damage?
CAD: hyperlipidemia d/t altered metabolism–> atherosclerosis–> MI
CVA: hyperlipidemia–> atherosclerosis–> CVA
PVD: damaged vessel in lumb—> chronic type caused by atherosclerosis
infections and diabetes?
high prevalence!
- foot infections and UTI common
- difficult to manage because of: vascular insufficiencies, impaired lymphocyte function, neuropathies prevent pt from noticing
diagnosing DM?
- history—> polyuria, polydipsia, polyphagia, weight loss, will not confirm but can make pt a candidate
- BG levels: random BG, fasting BG, glucose tolerance test
- –> random and IGT will be above 11, fassting above 7
- Hba1c > 6.5%: hemoglobin has highest affinity for glucose of all the humoglobin subclasses, measure hyperglycemia over last 3-4 months, monitors sucess of treatment
treatment of DM?
- modify lifestyle: eg improved diet, weight loss, activity
- glycemic control with drugs
- oral hypoglycemics in type 2
- insulin in type 1
why is oral hypoglycemics used in type 2 and what drug
relative deficiency of insulin, so it stimulates release of insulin from beta cells in the pancreas
increases tissue response to insulin (sensitizes body cells to action of insulin)
decreases hepatic glucogenesis (decrease production and release of glucose by liver)
METFORMIN
metformin rules?
give if hba1c is 7% after 2-3 months of lifestyle modification
give metformin AND insulin if >9% after
