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server/evaluate/reference_texts/ref_sample_3.txt

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+learning medicine is hard work osmosis
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+in diabetes mellitus your body has
+
+trouble moving glucose which is the type
+
+of sugar from your blood into your cells
+
+this leads to high levels of glucose in
+
+your blood and not enough of it in your
+
+cells and remember that your cells need
+
+glucose as a source of energy so not
+
+letting the glucose enter means that the
+
+cells star for energy despite having
+
+glucose right on their doorstep in
+
+general the body controls how much
+
+glucose is in the blood relative to how
+
+much gets into the cells with two
+
+hormones insulin and glucagon insulin is
+
+used to reduce blood glucose levels and
+
+glucagon is used to increase blood
+
+glucose levels both of these hormones
+
+are produced by clusters of cells in the
+
+pancreas called islets of langerhans
+
+insulin is secreted by beta cells in the
+
+center of these islets and glucagon is
+
+secreted by alpha cells in the periphery
+
+of the islets insulin reduces the amount
+
+of glucose in the blood by binding to
+
+insulin receptors embedded in the cell
+
+membrane of various insulin responsive
+
+tissues like muscle cells in adipose
+
+tissue when activated the insulin
+
+receptors cause vesicles containing
+
+glucose transporter that are inside the
+
+cell to fuse with the cell membrane
+
+allowing glucose to be transported into
+
+the cell glucagon does exactly the
+
+opposite it raises the blood glucose
+
+levels by getting the liver to generate
+
+new molecules of glucose from other
+
+molecules and also break down glycogen
+
+into glucose so that I can all get
+
+dumped into the blood diabetes mellitus
+
+is diagnosed when blood glucose levels
+
+get too high and this is seen among 10
+
+percent of the world population there
+
+are two types of diabetes type 1 and
+
+type 2 and the main difference between
+
+them is the underlying mechanism that
+
+causes the blood glucose levels to rise
+
+about 10% of people with diabetes have
+
+type 1 and the remaining 90% of people
+
+with diabetes have type 2 let's start
+
+with type 1 diabetes mellitus sometimes
+
+just called type 1 diabetes in this
+
+situation the body doesn't make enough
+
+insulin the reason this happens is that
+
+in type 1 diabetes there's a type 4
+
+hypersensitivity response or a cell
+
+mediated immune response where a
+
+person's own T cells at
+
+the pancreas as a quick review remember
+
+that the immune system has T cells that
+
+react to all sorts of antigens which are
+
+usually small peptides polysaccharides
+
+or lipids and that some of these
+
+antigens are part of our own body cells
+
+it doesn't make sense to allow T cells
+
+that will attack our own cells to hang
+
+around until there's this process to
+
+eliminate them called self tolerance in
+
+type 1 diabetes there's a genetic
+
+abnormality that causes a loss of self
+
+tolerance among T cells that
+
+specifically target the beta cell
+
+antigens losing self tolerance means
+
+that these T cells are allowed to
+
+recruit other immune cells and
+
+coordinate an attack on these beta cells
+
+losing beta cells means less insulin and
+
+less insulin means that glucose piles up
+
+in the blood because it can't enter the
+
+body's cells one really important group
+
+of genes involved in regulation of the
+
+immune response is the human leukocyte
+
+antigen system or HLA system even though
+
+it's called a system it's basically this
+
+group of genes on chromosome 6 that
+
+encode the major histocompatibility
+
+complex or MHC which is a protein that's
+
+extremely important in helping the
+
+immune system recognize foreign
+
+molecules as well as maintaining self
+
+tolerance MHC is like the serving
+
+platter that antigens are presented to
+
+the immune cells on interestingly people
+
+with type 1 diabetes often have specific
+
+HLA genes in common with each other one
+
+called
+
+HLA dr3 and another called HLA dr4 but
+
+this is just a genetic clue right
+
+because not everyone with HLA dr3 and
+
+HLA dr4 develops diabetes in diabetes
+
+mellitus type 1 destruction of beta
+
+cells usually starts early in life but
+
+sometimes up to 90% of the beta cells
+
+are destroyed before symptoms crop up
+
+for clinical symptoms of uncontrolled
+
+diabetes that all sound similar our
+
+polyphagia glycosuria polyuria and
+
+polydipsia let's go through them one by
+
+one even though there's a lot of glucose
+
+in the blood it cannot get into the
+
+cells which leaves cells starved for
+
+energy so in response adipose tissue
+
+starts breaking down fat called
+
+lipolysis
+
+and muscle tissue starts breaking down
+
+proteins both of which results in weight
+
+loss for someone with uncontrolled
+
+diabetes this catabolic state leaves
+
+people feeling hungry
+
+also known as poly fascia Faiza means
+
+eating and poly means a lot now with
+
+high glucose levels that means that when
+
+blood gets filtered through the kidneys
+
+some of it starts to spill into the
+
+urine called glycosuria glyco surfers to
+
+glucose and urea the urine since glucose
+
+is osmotically active water tends to
+
+follow it resulting in an increase in
+
+urination or polyuria poly again refers
+
+to a lot and urea again refers to urine
+
+finally because there's so much
+
+urination people with uncontrolled
+
+diabetes become dehydrated and thirsty
+
+or polydipsia poly means a lot and dip
+
+SIA means thirst even though people with
+
+diabetes are not able to produce their
+
+own insulin they can still respond to
+
+insulin so treatment involves lifelong
+
+insulin therapy to regulate their blood
+
+glucose levels and basically enable
+
+their cells to use glucose
+
+one really serious complication with
+
+type 1 diabetes is called diabetic
+
+ketoacidosis or DKA to understand it
+
+let's go back to the process of
+
+lipolysis where fat is broken down into
+
+free fatty acids after that happens the
+
+liver turns the fatty acids into ketone
+
+bodies like Osito acetic acid in beta
+
+hydroxy butyrate acid a seed of acetic
+
+acid is a keto acid because it has a
+
+ketone group in a carboxylic acid group
+
+beta hydroxy rhetoric acid on the other
+
+hand even though it's still one of the
+
+ketone bodies isn't technically a keto
+
+acid since its ketone group has been
+
+reduced to a hydroxyl group these ketone
+
+bodies are important because they can be
+
+used by cells for energy but they also
+
+increase the acidity of the blood which
+
+is why it's called ketoacidosis and the
+
+blood becoming really acidic can have
+
+major effects throughout the body
+
+individuals can develop custom all
+
+respiration which is a deep and labored
+
+breathing as the body tries to move
+
+carbon dioxide out of the blood in an
+
+effort to reduce its acidity cells also
+
+have a transporter that exchanges
+
+hydrogen ions or protons for potassium
+
+when the blood gets acidic it's by
+
+definition loaded with protons that get
+
+sent into cells while potassium gets
+
+sent into the fluid outside cells
+
+another thing to keep in mind is that in
+
+addition to helping glucose enter cells
+
+insulin stimulates the sodium potassium
+
+ATPase --is which help potassium get
+
+into the cells and so without insulin
+
+more potassium stays in the fluid
+
+outside cells both of these mechanisms
+
+lead to increased potassium in the fluid
+
+outside cells which quickly makes it
+
+into the blood and causes hyperkalemia
+
+the potassium is then excreted so over
+
+time even though the blood potassium
+
+levels remain high over all stores of
+
+potassium in the body which include
+
+potassium inside cells starts to run low
+
+individuals will also have a high anion
+
+gap which reflects a large difference in
+
+the unmeasured negative and positive
+
+ions in the serum largely due to the
+
+build-up of ketoacids
+
+diabetic ketoacidosis can happen even in
+
+people who have already been diagnosed
+
+with diabetes and currently have some
+
+sort of insulin therapy
+
+in states of stress like an infection
+
+the body releases epinephrine which in
+
+turn stimulates the release of glucagon
+
+too much glucagon can tip the delicate
+
+hormonal balance of glucagon and insulin
+
+in favor of elevating blood sugars and
+
+can lead to a cascade of events we just
+
+described increased glucose in the blood
+
+loss of glucose in the urine loss of
+
+water dehydration and in parallel and
+
+need for alternative energy generation
+
+of ketone bodies and ketoacidosis
+
+interestingly both ketone bodies break
+
+down into acetone and escape as a gas by
+
+getting breathed out the lungs which
+
+gives us sweet fruity smell to a
+
+person's breath in general though that's
+
+the only sweet thing about this illness
+
+which also causes nausea vomiting and if
+
+severe mental status changes and acute
+
+cerebral edema
+
+treatment of a DKA episode involves
+
+giving plenty of fluids which helps with
+
+dehydration insulin which helps lower
+
+blood glucose levels and replacement of
+
+electrolytes like potassium all of which
+
+help to reverse the acidosis now let's
+
+switch gears and talk about type 2
+
+diabetes which is where the body makes
+
+insulin but the tissues don't respond as
+
+well to it the exact reason why cells
+
+don't respond isn't fully understood
+
+essentially the body's providing the
+
+normal amount of insulin but the cells
+
+don't move their glucose transporters to
+
+their membrane in response which
+
+remember is needed for the glucose to
+
+get into the cells these cells therefore
+
+have insulin resistance some risk
+
+factors for insulin resistance are
+
+obesity lack of exercise and
+
+hypertension the exact mechanisms are
+
+still being explored for example in
+
+excess of adipose tissue or fat is
+
+thought to cause the release of free
+
+fatty acids in so-called edible kinds
+
+which are signaling molecules that can
+
+cause inflammation which seems related
+
+to insulin resistance
+
+however many people that are obese are
+
+not diabetic so genetic factors probably
+
+play a major role as well we see this
+
+when we look at twin studies as well
+
+we're having a twin with type-2 diabetes
+
+increases the risk of developing type 2
+
+diabetes completely independently of
+
+other environmental risk factors in type
+
+2 diabetes since tissues don't respond
+
+as well to normal levels of insulin the
+
+body ends up producing more insulin in
+
+order to get the same effect and move
+
+glucose out of the blood
+
+they do this through beta cell
+
+hyperplasia an increased number of beta
+
+cells and beta cell hypertrophy where
+
+they actually grow in size all in this
+
+attempt to pump out more insulin this
+
+works for a while and by keeping insulin
+
+levels higher than normal blood glucose
+
+levels can be kept normal called normal
+
+glycemia now along with insulin beta
+
+cells also secrete islet amyloid
+
+polypeptide or amylin so while beta
+
+cells are cranking out insulin they also
+
+secrete an increased amount of amylin
+
+over time Emlyn builds up and aggregates
+
+in the islets this beta cell
+
+compensation though is not sustainable
+
+and over time those maxed out beta cells
+
+get exhausted and they become
+
+dysfunctional and undergo hypo trophy
+
+and get smaller as well as hypoplasia
+
+and die off as beta cells are lost in
+
+insulin levels decrease glucose levels
+
+in the blood start to increase in
+
+patients develop hyperglycemia which
+
+leads to similar clinical signs that we
+
+mentioned before like Paul aphasia
+
+glycosuria polyuria polydipsia but
+
+unlike type 1 diabetes there's generally
+
+some circulating insulin in type 2
+
+diabetes from the beta cells that are
+
+trying to compensate for the insulin
+
+resistance this means that the insulin
+
+glucagon balances such that diabetic
+
+ketoacidosis does not usually develop
+
+having said that a complication called
+
+hyperosmolar hyperglycemic state or HHS
+
+is much more common in type 2 diabetes
+
+than type 1 diabetes and it causes
+
+increased plasma osmolarity due to
+
+extreme dehydration and concentration of
+
+the blood to help understand this
+
+remember that glucose is a polar
+
+molecule that cannot passively diffuse
+
+across cell membranes which means that
+
+it acts as a solute so when levels of
+
+glucose are super high in the blood
+
+meaning it's a hyperosmolar State water
+
+starts to leave the body cells and enter
+
+the blood vessels leaving the cells were
+
+relatively dry in travailed rather than
+
+plump and juicy blood vessels that are
+
+full of water lead to increased
+
+urination and total body dehydration and
+
+this is a very serious situation because
+
+the dehydration of the body's cells and
+
+in particular the brain can cause a
+
+number of symptoms including mental
+
+status changes in HHS you can sometimes
+
+see mild ketone emia and acidosis but
+
+not to the extent that it's seen in DKA
+
+and in DKA you can see some hyper
+
+osmolarity so there's definitely overlap
+
+between these two syndromes
+
+besides type 1 and type 2 diabetes there
+
+are also a couple other subtypes of
+
+diabetes mellitus gestational diabetes
+
+is when pregnant women have increased
+
+blood glucose which is particularly
+
+during the third trimester although
+
+ultimately unknown the cause is thought
+
+to be related to pregnancy hormones that
+
+interfere with insulins action on
+
+insulin receptors also sometimes people
+
+can develop drug-induced diabetes which
+
+is where medications have side effects
+
+that tend to increase blood glucose
+
+levels the mechanism for both of these
+
+is thought to be related to insulin
+
+resistance like type 2 diabetes rather
+
+than an autoimmune destruction process
+
+like in type 1 diabetes diagnosing type
+
+1 or type 2 diabetes is done by getting
+
+a sense for how much glucose is floating
+
+around in the blood and has specific
+
+standards that the World Health
+
+Organization uses very commonly a
+
+fasting glucose test is taken where the
+
+person doesn't eat or drink except the
+
+water that's okay for a total of eight
+
+hours and then has their blood tested
+
+for glucose levels levels of 100
+
+milligrams per deciliter to 120
+
+five milligrams per deciliter indicates
+
+pre-diabetes and 126 milligrams per
+
+deciliter or higher indicates diabetes a
+
+non fasting a random glucose test can be
+
+done at any time with 200 milligrams per
+
+deciliter or higher being a red flag for
+
+diabetes another test is called an oral
+
+glucose tolerance test where person is
+
+given glucose and then blood samples are
+
+taken at time intervals to figure out
+
+how well it's being cleared from the
+
+blood the most important interval being
+
+two hours later levels of 140 milligrams
+
+per deciliter to 199 milligrams per
+
+deciliter indicate pre-diabetes
+
+and 200 or above indicates diabetes
+
+another thing to know is that when blood
+
+glucose levels get high the glucose can
+
+also stick to proteins that are floating
+
+around in the blood or in cells so that
+
+brings us to another type of test that
+
+can be done which is the hba1c test
+
+which tests for the proportion of
+
+hemoglobin in red blood cells that has
+
+glucose stuck to it called glycated
+
+hemoglobin hba1c levels of 5.7% 26.4%
+
+indicate pre-diabetes
+
+and 6.5 percent or higher indicates
+
+diabetes this proportion of glycated
+
+hemoglobin doesn't change day to day so
+
+it gives a sense for whether the blood
+
+glucose levels have been high over the
+
+past two to three months finally we have
+
+the c-peptide test which tests for
+
+byproducts of insulin production if the
+
+level of c-peptide is low or absent it
+
+means the pancreas is no longer
+
+producing enough insulin and the glucose
+
+cannot enter the cells
+
+for type one diabetes insulin is the
+
+only treatment option for type 2
+
+diabetes on the other hand lifestyle
+
+changes like weight loss and exercise
+
+along with a healthy diet and an oral
+
+anti-diabetic medication like metformin
+
+in several other classes can sometimes
+
+be enough to reverse some of that
+
+insulin resistance and keep blood sugar
+
+levels in check however if oral
+
+anti-diabetic medications fail type 2
+
+diabetes can also be treated with
+
+insulin something to bear in mind is
+
+that insulin treatment comes with a risk
+
+of hypoglycemia especially if insulin is
+
+taken without a meal symptoms of
+
+hypoglycemia can be mild like weakness
+
+hunger and shaking but they can progress
+
+to a loss of consciousness in seizures
+
+in severe cases in mild cases drinking
+
+juices or eating candy or sugar might be
+
+enough to bring blood sugar up but in
+
+severe cases intravenous glucose should
+
+be given as soon as possible
+
+the FDA has also recently approved
+
+intranasal glucagon as a treatment for
+
+severe hypoglycemia all right now over
+
+time high glucose levels can cause
+
+damage to tiny blood vessels while the
+
+micro vasculature in arterioles a
+
+process called hyaline
+
+arteriolosclerosis is where the walls of
+
+the arterioles develop hyaline deposits
+
+which are deposits of proteins and these
+
+make them hard and inflexible in
+
+capillaries the basement membrane can
+
+thicken and make it difficult for oxygen
+
+to easily move from the capillary to the
+
+tissues causing hypoxia
+
+one of the most significant effects is
+
+that diabetes increases the risk of
+
+medium and large arterial wall damage
+
+and subsequent atherosclerosis which can
+
+lead to heart attacks and strokes which
+
+are major causes of morbidity and
+
+mortality for patients with diabetes in
+
+the eyes diabetes can lead to
+
+retinopathy and evidence of that can be
+
+seen on a fundus copic exam that shows
+
+cotton-wool spots or flare hemorrhages
+
+and can eventually cause blindness in
+
+the kidneys the a ferrant and efferent
+
+arterioles as well as the glomerulus
+
+itself can get damaged which can lead to
+
+an F Radek syndrome that slowly
+
+diminishes the kidneys ability to filter
+
+blood over time and can ultimately lead
+
+to dialysis diabetes can also affect the
+
+function of nerves causing symptoms like
+
+a decrease in sensation in the toes and
+
+fingers sometimes called a stocking
+
+glove distribution as well as causes the
+
+autonomic nervous system to malfunction
+
+and that system controls a number of
+
+body functions
+
+everything from sweating to passing gas
+
+finally both the poor blood supply and
+
+nerve damage can lead to ulcers
+
+typically on the feet that don't heal
+
+quickly and can get pretty severe and
+
+need to be amputated these are some of
+
+the complications of uncontrolled
+
+diabetes which is why it's important to
+
+diagnose and control diabetes through a
+
+healthy lifestyle medications to reduce
+
+insulin resistance and even insulin
+
+therapy if beta cells have been
+
+exhausted while type 1 diabetes cannot
+
+be prevented type 2 diabetes can in fact
+
+many people with diabetes can control
+
+their blood sugar levels really
+
+effectively and live a full and active
+
+life without any of the complications
+
+thanks for watching if you're interested
+
+in a deeper dive on this topic take a
+
+look at as Moses org where we have
+
+flashcards questions and other awesome
+
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