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Flashcards in digestive phys and glucose metabolism Deck (103):

Pathway of digestion

- ingestion
- mechanical digestion: chewing, churning of stomach and segmentation in stomach
- propulsion: swallowing, peristalsis (esophagus, stomach, small intestine, and large intestine)
- absorption in small intestine and large intestine (mostly water)
- defecation


The pancreas (location, function, anatomy)

- gland with both exocrine and endocrine fxns
- 6-10 inches in length
- 60-100 g in weight
- location: retro-peritoneum, 2nd lumbar vertebral level
- extends in oblique, and transvere position
- parts of the pancreas: head, neck, body and tail


Embryology of pancreas?

- endodermal origin
- develops from ventral and dorsal pancreatic buds (develop independently)
- ventral bud becomes the uncinate process and inferior head of pancreas
- dorsal bud becomes superior head, neck, body, and tail
- ventral bud duct fuses with dorsal bud duct to brecome main pancreatic duct (wirsung)
- pancreas divisum when fails to fuse


What is the definition of exocrine?

- secreeting outwardly via a duct


What is the definition of endocrine?

- secreting inwardly, applied to organs and structures whose functions is to secrete into the blood or lymph a hormone that has a specific effect on another organ or part


Where is there a large capillary network in the pancreas?

- in the islet of langerhans (endocrine part of pancreas)
- islets of langerhan cells are not part of duct system


What cells make up the exocrine part of pancreas?

- acinar cells: secrete pancreatic enzymes into pancreatic duct


What is function of islet of langerhan cells?

- secrete endocrine hormones into blood vessels


Anatomy of islet of langerhans?

- insulin producing B cells are in the center closest to the blood supply and are surrounded by glucagon producing alpha cells. On outside are the delta cells which make somatostatin (produces GH), and the PP cells (gamma cells) that make pancreatic polypeptide


histology of endocrine part of pancreas?

- accounts for only 2% of pancreatic mass
- nest of cells: islet of langerhans


Four major cell types of the endocrine pancreas?

- alpha cells: secrete glucagon
- beta cells: secrete insulin
- delta cells: secrete somatostatin
- F cells (gamma cells) secrete pancreatic polypeptide


Organization of acinar cells and iselt of langerhans?

- islet of langerhans is surrounded by pancreatic acinar cells. The islet cells form cords separated by blood capillaries. The islet is surrounded by reticular fibers separating it from acinar cells


What is function of alpha cells?

- release glucagon; main action is to produce an increase in blood glucose: they do this by -
breakdown of glycogen, stimulates gluconeogenesis (inhibits glycogenesis), increases transport of AA into the liver and stimulates their conversion to glucose
- high levels activate adipose cell lipase making fatty acids available for use as energy


What stimulates the release of glucagon?

- released into portal circulation in response to low glucose levels in blood, stimulated by high concentrations of AA and by strenuous exercise


Metabolic effects of glucagon?

- increase glucose, increase ketoacids,
and decrease amino acids


What factors stimulate glucagon secretion?

- hypoglycemia
- amino acids: aginine and alanine
- GI hormones: CCK, gastrin
- fasting
- exercise
- neural influences: vagal activity acetylcholine, sympathetic stim (NE, E)


What factors inhibit glucagon secretion?

- glucose
- somatostatin
- insulin (direct effect)
- GI hormones: secretin, GLP-1
- free fatty acids
- ketoacids
- neural influences: alpha-adrenergic stim


Effect of DPP-4 inhibitors

- block DPP-4 and decrease glucose
- DPP-4 enzyme inactivates GLP-1, and incretin this stimulates insulin release (stim. beta cell production) and inhibits glucagon release which lowers the blood glucose
(DPP-4 is essential in formation of glucose)
- impt impact in DM II, won't work on DM I because there are no beta cells to stimulate


Fuel metabolism during the anabolic state (building up)

- hormones: increased insulin and decreased glucagon
- fuel source is diet
- process: glycogen synthesis, triglyceride synthesis, and protein synthesis


Fuel metabolism in catabolic state?

- catabolism: decreased insulin, increased glucagon
- fuel source: storage depots, process: glycogenolysis, lipolysis, proteolysis, ketogenesis (formation of ketones)


Metabolic effects of Epi?

- increased glucose, free fatty acids from triglycerides, and increased ketoacids from free fatty acids


What hormones promote glucose production (liver)?

- Glucocorticoids, GH, glucagon, Epi
- insulin will inhibit glucose production


What hormone promotes glucose consumption in muscle and adipose tissue?

- insulin
- glucocorticoids, and GH have inhibitory effect on glucose consumption


Function of Beta cells?

- produce insulin: lowers blood glucose by: promoting uptake of glucose by target cells, provides for glucose storage as glycogen, prevents fat and glycogen breakdown
- inhibits gluconeogenesis and increases protein synthesis
- promotes fat storage by increasing transport of glucose by increasing transport of glucose into fat cells
- increases triglycerides synthesis
- Beta cells produce pro-insulin formed by an A and B cahin separated by inactive C-peptide chain which is cleaved by enzymes in the beta cells and packaged in secretory granules, insulin enters protal circulation where 50% used or degraded, 1/2 life is 15 minutes


Where do the main steps of insulin synthesis and secretion by a B cell take place?

- islets of Langerhands
- RER: synthesis of proinsulin
- small transfer vesicle - transport of proinsulin to Golgi
- golgi secretes secretory granules and conversion of proinsulin to insulin occurs


Insulin and glucose relationship in circulation?

- insulin directly enters protal venous circulation before peripheral cirulation: 2/3 of glucose is stored as glycogen in the liver, and other glucose is released back into blood to keep blood glucose at steady state after intake


What is a major regulator of insulin?

- glucose
- in pancreatic beta cell glucose transporters - allow influx of glucose: glucokinase
- results in closure of K+ channels and opening of Ca channels allowing secretion of insulin by exocytosis


What factors stimulate insulin secretion?

- glucose: mannose and galactose
- amino acids
- free fatty acids, keto acids
- glucagon (direct and indirect effects)
- GI hormones: GLP-1 and GIP
- neural influences: vagal activity (acetylcholine), B-adrenergic stimulation
- sulfonylurea drugs


What factors inhibit insulin secretion?

- somatostatin (inhibits both glucagon and insulin)
- fasting
- exercise
- neural influences: sympathetic activity: alpha-adrenergic stimulation (NE and E)
- Leptin: released from fat


What is the effect of insulin on carbohydrates?

- carbs from a meal release glucose:
- stimulates secretion of insulin
- causes uptake and storage of glucose in all tissues
- in muscle if not used glycogen is stored
- in liver stored as glycogen, once liver has stored all the glycogen it can, insulin promotes conversion of glucose to fatty acids


Metabolic effects of insulin

- decrease glucose, free fatty acids, ketoacids (fatty acids aren't being broken down), and amino acids (proteins being stored in muscles)


Insulin effect on muscle?

- increase GLUT4 transporters
- increase glycogen
- increase glycolysis (glucose to pyruvate)
- increased protein synthesis, decreased protein degradation
- increas in triglycerides (FAs from circulation)


Effect of insulin on liver?

- GLUT2 transporter: increase glucokinase
- increase glycogen
- decrease glucose release: decrease G6Pase
- increase glycolysis: increases acetyl CoA, increases FA synthesis
- increases TG storage and export (VLDLs)
- increase protein synthesis, and decreases protein degradation


Insulin on fat metabolism?

first insulin increased the utilization of glucose (uptake) by most of the body's tissues, which decreases utilization of fat
- once liver glycogen is maxed all add. glucose forms fatty acids
- fatty acids in the liver form TGs which are released into blood stream and are transported to adipose tissue
- once there insulin activates LPL which splits TGs into fatty acids again for them to be absorbed into adipose cells


What promotes break down of TGs to fatty acids?

- Epi, T3, Cortisol, GH


What promotes TG production from fatty acids?

- insulin


Insulin impact on adipocytes?

- increase GLUT4 transporters
- increase glycolysis: increase alpha-glycerol phosphate, increase acetyl CoA, and increase FA synthesis
- increase TGs: decrease hormone sensitive lipase and increase LPL


Insulin effects on AAs?

- stimulates transport of many AA into the cells
- inhibits the catabolism of proteins especially in muscles cells
- in the liver depresses rate of gluconeogenesis


- What will respond to low plasma glucose
- what will respond to high plasma glucose?

- low glucose: glucagon response
- high glucose: insulin response


Hormonal responses to specific glucose concentrations?

- 80-85 mg/dl: decreased insulin
- 65-70: increased glucagon, increased Epi, and increased cortisol and GH


CNS responses to specific glucose concentrations?

65-70: decreasd glucose uptake
50-55 (60): sympotoms
50: decreased cognition
40: coma
30: convulsion
20: permanent brain damage


Function of delta cells?

- secrete prosomatostatin that is processed soatostatin-14 and somatostatin-28
- actions: inhibits secretion of growth hormone and thyro-tropin from pituitary
- inhibits insulin and glucagon in the endocrine pancreas
- inhibits gastrin release and gastric secretion from parietal cells
- inhibits exocrine secretion of pancreas
- circulating half life: 3 min


Pancreatic exocrine functonal unit?

- acinus and its draining ductule with cetroacinar cell b/t acinar cell and ductal epithelium


What is the acinar cell of the pancreas?

- basolateral membrane receptors for hormones and neurotransmitters
- basal part: nucles and RER for protein synthesis (active part of the cell)
- apical-zymogen granules to store digestive enzymes
- apical surface: microvilli for exocytosis


WHat is the ductal epithelium of the pancreas?

- abundant mitochondria for energy transport
- carbonic anhydrase important to secrete bicarb


Histology of exocrine pancreas, what are the 2 major components?

- acinar cells and ducts
- constitute 80-90% of pancreatic mass
- acniar cells secrete the digestive enzymes
- 20-40 acinar cells coalesce into a unit calle the acinus
- centroacinar cell (2nd cell type in the acinus) is responsible for fluid and electrolyte secretion by the pancreas


Ductular system in exocrine pancreas?

- ductular system: network of conduits that carry the exocrine secretions into the duodenum
- acinus - to the small intercalated ducts - to the interlobular duct - to the pancreatic duct of wirsung
- interlobular ducts contribute to fluid and electrolyte secretion along with the centroacinar cells


Pancreatic secretion of Digestive enzymes? activation?

- digestive enzymes secreted from pancreatic acini:
in the pancreas the enzymes are in inactive form such as trypsinogen and procarboxypolypeptidase A and B
in the intestinal lumen glycoprotein peptidase activates trypsinogen then trypsin activits the other inactive proenzymes (if active in pancreas - would destroy it)


Enzyme actions of exocrine pancreas?

- trypsin and chymotrypsin split proteins into peptides
- carboxypolypeptidase splits peptides into some amino acids
- pancreatic amylase hydrolyzes glycogen and carbohydrates into disacharides and trisaccharides
- Lipase hydrolyzes fat into FAs and monglycerides
- cholesterol esterase hydrolyzes cholesterol esters
- phospholipase splits fatty acids from phospholipids

- Pancreatic amylase and lipase increase in blood when problem with pancreas


What is secreted in large volumes by small ductules of the exocrine pancreas?
purpose of this?

- sodium bicarbonate is secreted in large volumes by small ductules leading from acini
- the ductule cells are stimulated by secretin released when acidic chyme enters the small intestine, they then release large volumes of water and bicarb which makes the contents of the small intestine more alkaline so the pancreatic enzymes work better and more pancreatic enzymes flow out with water and bicarb
- combined enzymes and bicarb flow through pancreatic duct joins hepatic duct and empties into duodenum through papilla of Vater, surrounded by sphincter of Oddi

- also alkaline so you don't get ulcers from hydrochloric acid


Regulation of pancreatic secretion main players?

- acetylcholine: from vagal nerve - moderate amounts of enzymes secreted in acini (20%) - during gastric and cephalic phase
- secretin: from upper intestinal mucosa - stimulates release of water and bicarb from ductules so gets enzymes out of acini - during intestinal phase (alkaline pH)
- cholecystokinin: from duodenal and upper jejunal mucosa: secreted when food enters - causes greater release of enzymes (80%)
- Trypsin inhibitor: in acini prevents activation of trypsinogen and since trypsin activates other enzymes this prevents enzymes from being activated and digesting pancreas


Process of activation of pancreatic juice?

- vagal stimulation releases enzymes into acini
- secretin causes copious secretion of pancreatic fluid and bicarb; cholecystokinin causes secretion of enzymes
- acid from stomach releases secretin from wall of duodenum; fats and amino acids cause release of cholecystokinin
- secretin and cholecystokinin is absorbed into the blood stream


What is pancreatitis?

- if pancreas becomes damaged or duct blocked then secretions back up and overwhelm trypson inhibitor and pancreatic secretions become activated and digest pancreas causing acute pancreatitis - very serious condition


Reaction to low blood glucose on muscle, pancreas and glycogen and adipose cells

pancreas decreases insulin secretion which helps to also trigger muscle and glycogen
- muscle: proteins broken down
- adipose cells: glycerol and fatty acids released
- glycogen: glucose is released
** in a fasted state: substrates for glucose synthesis (gluconeogenesis) are released from storage


What are signs and symptoms of hypoglycemia?

- SNS stimulation:
sweating, palpitations, tremor, nervousness, irritability, paresthesias, hunger, N/V

- other sxs:
HA, tired and drowsy, dizzy and fainting, blurred vision, confusion, abnormal behavior, seizures, coma


Sympathoadrenal sxs of hypoglycemia?

- sweating, nausea, hunger
- warmth, hunger
- tremor, palpitations, tachycardia (first sxs presented)


Neuroglycopenic sxs of hypoglycemia?

- fatigue, HA, drowsiness, dizziness, visual disturbances, difficulty speaking, inability to concentrate, abnormal behavior, loss of memory, confusion, loss of consciousness, seizures


What is Whipple's triad?

- grouping of sxs consisten with hypoglycemia
- low plasma glucose (


How common is hypoglycemia, how fast does it occur?

- rapid
- emergency (most common endo emergency)
- 10-30% of type 1 diabetics/ year
- classification: reactive/ functional


Causes of reactive hypoglycemia?

- external influences:
severe exercise
med use: insulin (timing and dose), B-blockers (will hide SNS effects), bacterium, haloperidol, MAO inhibitors, sulfonylureas


Causes of functional hypoglycemia?

- hepatic and renal dysfunction
- malnutrition
- endocrinopathies: adrenal (glucocorticoid) insufficiency, GH deficiency, glucagon deficiency, pituitary disease ( decreased corticotropin/GH)
- pancreatic tumors: insulonoma
- alcohol consumption (inhibits gluconeogenesis)


Clinical presentation of hypoglycemia?

- fasting hypoglycemia is assoc' with sxs of neuroglycopenia, whereas postprandial hypoglycemia is more likely to produce adrenergic responses
- neuroglycopenic manifestations are result of decreased glucose supply to CNS and PNS, including HAs, confusion, slurred speech, neuromuscular sxs, seizures coma
- adrenergic response: caused by an abrupt decrease in glucose level and counter-regulatory release of epi, resulting in sudden onset of hunger, diaphoresis, weakness and palpitation


hypoglycemic coma?

- recovery from hypoglycemia may be delayed because of cerebral edema. Unconsciousness lasting more than 30 minutes after plasma glucose is corrected is called posthypoglycemic coma, IV mannitol ( will draw out edema from brain) , or glucocorticoids, or both can be used along with maintenance of normal plasma glucose levels


What is hypoglycemic unawareness?

- 50% of type 1 pts undergo diminution in their epi response to hypoglycemia
- further pts lose the autonomic warning sxs of hypoglycemia and may recognize (or even fail to recognize) the condition only when somatic neuro function becomes impaired (neuroglycopenia)
- usually associated with duration of diabetes and autonomic neuropathy
- may also occur when pts are switched to intensive insulin regimens
- the introduction of intensified diabetes tx regimens can lower the glucose levels that triggers epi release and adrenergic sxs
- b blockers blunt cardiac response to hypoglycemia


How are hypoglycemic disorders managed?

- in these situations: if pts can ingest food, the hypoglycemia generally responds well to oral glucose (orange juice) or carb-containing products
- if the pt isn't able or unwilling to ingest food because of mental changes, glucagon is given SC or IM may be give outside of hospital setting
- in the hospital setting: the std tx in these situations is IV glucose admin, which is followed by subsequent glucose infusion, feeding or both
- 1 amp of D 50


What is the usual cause of hypoglycemia?

-- hypoglycemia in insulin-treated diabetic patients is usually due to omission of a meal while insulin was given, an error in medication or unproductive absorption of food in a pt (gastroparesis)


What is important education to give to your patient about diabetes?

- etiologies of hypoglycemia
- preventive measures
- appropriate adjustments to meds
- diet and exercise regimen


Body's reaction to high blood glucose? (right after eating a meal)

- pancreas: increases secretion of insulin which in turn also helps stimulate glycogen formation and glucose absorption into the muscle
- muscle: glucose will be absorbed
- glucose to glycogen
- insulin also stimulates glucose to be absorbed in the adipose cells


1st, 2nd, and 3rd priorities of absorbed glucose?

- 1st: glycogen storage: glycogen storage - stored in muscle and liver
- 2nd: provide energy, oxidized to ATP
- 3rd: stored as fat: only ecess glucose, stored as triglycerides in adipose


Glucose utilzation?

- adipose tissue and turned into glycogen for energy stores
- turned into ribose-5-phosphate for pentose phosphate pathway
- turned into pyruvate for glycolysis


Metabolic consequences of insulin deficiency - DM

- increased blood glucose concentration
- increased blood FFA and ketoacid concentration - fat depletion
- increased blood amino acid concentration - protein depletion


Fluid and electrolyte consequences of DM?

- metabolic acidosis - DKA
- glycosuria and osmotic diuresis
- increased osmolarity
- hyperphagia
- polydypsia
- hypovolemic and hypotension
- coma and death if not tx


Pathophys of Type 1 DM?

- autoimmune destruction of B-cells
- insulinopenia
- ketonemia (ketone overload)
- dependent on insulin to sustain life and prevent ketoacidosis


Pathophys of Type II DM (NIDDM)

- insulin resistance
- normal or elevated insulin initially and then relative insulin deficiency
- increased hepatic glucose production
- not as prone to ketoacidosis as type 1
- most pts are obese
- may require insulin to control hyperglycemia


Progression of type 1 diabetes?

- more acute presentation
- usually genetic predisposition then there is an immunologic trigger and decrease of B cell mass - get to such a small number of working beta cells that diabetes presents (acutely, age range is usually 15-20)


What happens in the progression of type II diabetes?

- insulin is capable of uptake of glucose but then gets to point where insulin loses effect no matter the concentration -- body becomes resistant to insulin and then insulin secreting beta cells eventually get burnt out. (see first: glucose intolerance, and obese changes to overt diabetes + increased insulin to diabetes + decreased insulin)


IDDM facts: % of total diabetics, age at onset, body build, severity, insulin dependency, oral hypoglycemic effect?

- %: 5-10 of total diabetics
- 15 yo age at onset
- body build: normal to thin
- severity: severe
- insulin dependency: almost all
- oral hypoglycemics: few respond


NIDDM facts: % of total diabetics, age at onset, body build, severity, insulin dependency, oral hypoglycemic effect?

- %: 85-90% of total diabetics
- 40+ age at onset
- obese body build
- severity: mild
- insulin dependency: 25-30%
- oral hypoglycemics: 50% respond


Ketoacidosis in IDDM and NIDDM?

- common in IDDM
- uncommon in NIDDM


Onset of disease of IDDM and NIDDM?

- rapid in IDDM
- slow in NIDDM


Complication and stability in IDDM and NIDDM?

- IDDM: 90% in 20 years, unstable
- NIDDM: less common, stable


Family history factor in IDDM and NIDDM?

- IDDM: common
NIDDM: more common


Insulin receptor defects in IDDM and NIDDM?

- IDDM: uncommon
- NIDDM: common (resistance)


What is diabetic ketoacidosis and who is it most commonly seen in?

- most commonly seen in type 1
- can happen with type 2 though
- onset: hours to days
- defined as being present with absolute or relative insulin deficiency when the following criteria are met:
-blood glucose levels> 250
- ketosis: ketones in urine and blood
- Acidosis: pH


Associated metabolic and plasma abnormalities in DKA?

- dehydration
- increased osmolality (15): metabolic acidosis
- increased serum amylase
- elevated white count (if infection is the culprit)
- hyperTGemia


Pathophysiology of DKA?

- stress on the body this results in increase of catecholamines and increase GH - this leads to increase glucagon and decreased insulin which then causes hyperglycemia + ketosis - leads to osmotic diuresis, dehydration and metabolic acidosis


Precipitating factors in DKA?

- infection, new onset diabetes, insulin admin, stress
- (first onset of type 1 could be ketoacidosis)


Sxs of DKA?

- N/V
- thirst, polydypsia
- polyuria
- abdominal pain
- weakness
- fatigue
- anorexia


Signs of DKA?

- tachycardia
- orthostatic hypotension
- poor skin turgo
- dry skin and mucous membranes
- kussmaul's respirations
- hypothermia
- fruity breath (ketones)
- altered mental status or coma


At what plasma osomolarity do you go from alert to obtunded, stuperous, comatose?

- alert: 315
- obtunded: 321
- stuperous: 343
- comatose: 369


What counter regulatory hormones can cause hyperglycemia (DKA) in increased amounts?
What else occurs in DKA?

- cortisol
- GH
- glucagon
- Epi

- increased insulin deficiency
- decreased peripheral glucose utilization


electrolyte osmolarity shifts in DKA?

- hyperosmolarity due to increased blood glucose levels
- osmotic diuresis leads to dehydration
- hyperosmolar state leads to water shift and K+ from intracellular to extracellular
- serum Na+ is low to normal despite diuresis
- serum K+ is normal or elevated (d/t intracellular fluid shift)
- metabolic acidosis from ketone production leads to marked decrease in serum bicarb


Production of ketones in DKA?

- body breaks down free FAs to try to utilize as energy, leading to produciton of ketones
- increased breakdown of fatty acids also leads to hypertriglyceridemia

- anion gap: be on CMP


What should you order if you suspect DKA?

- serum osmolarity
- lipid profile
- amylase/lipase
- CBC with diff
- serum acetone
- urine glucose/ketones
- ABGs


What are the goals of therapy in DKA? restoring circulatory volume -

- restore cirulatory volume:
NS or 1/2 NS: depending on NA+ level
- 1 L/hr x 2 hours
- 250-500 ml/hr for 2-4 hours
- watch serum Na+ may need to switch IV to 1/2 NS
- fluid replacement will lower blood glucose levels thru dilution, lower osmolarity and ketones and improve peripheral utilization of ketones and glucose
- switch to 5% dextrose solution when glucose is


Goals of therapy - insulin therapy?

- insulin therapy: 10 U IV bolus of regular insulin
- cont. insulin drip at 6 U/hr or 0.1U/kg/hr
- dont decrease serum glucose too fast
- check blood sugars hourly
- insulin facilitates peripheral uptake of ketones and glucose and inhibits hepatic glucose production


Goals of therapy for DKA: K+ replacement?

- K+ level will be normal or high at first
- dilution of plasma with fluid admin will lower K+
- K+ will follow insulin and glucose into cell
- K+ replacement based on q 2 hr serum measurements
- initially replace with K+ boluses
- eventually can add K+ to IV solution


Bicarb replacement? When should it happen?

- use with extreme caution and only consider if pH


DKA pt: When should insulin be changes to SQ?

- when the pt can eat and drink


What is hyperglycemic hyperosmolar nonketotic syndrome?

- occurs almost exclusively in type 2
- elderly and physically impaired
- limited access to free water
- dist. from DKA by:
high hyperglycemia more than 600
relative absence of acidosis and ketones
greater degree of dehydration


Signs and symptoms of hyperglycemic hyperosmolar nonketotic syndrome?

- severe dehydration:
dry skin and mucous membranes, extreme thirst
- Neuro signs:
lethargy to coma
sensory impairment
hyperthermia (could be mistaken for a stroke)


Lab findings in Hyperglycemic hyperosmorlar nonketotic syndrome?

- blood glucose of more than 600
- serum osmolarity greater than 320
- serum Na+ normal to high (135-145)
- serum K+ normal 94-5)
- serum bicarb ( greater than 15)
- pH greater than 7.3
- ketones: negative

- can be complicated by thromboembolic events arising because of high serum osmolarity
- prognosis less favorable than DKA


Tx of hyperglycemic hyperosmolar nonketotic syndrome?

- tx:
IV fluid replacement - slower rate than DKA, greater volume needed, rehydrate over 36-72 hours, pts usually older and have co-morbidities
- insulin replacement starts after rehydration is in progress: more sensitve to insulin so may need to lower doses

- heparin: prophylaxis d/t predisposition to vascular thrombosis from hyperosmol state