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253 Cards in this Set
- Front
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Langerhans islets
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1-2% of the volume of the pancreas
They are most numerous in the tail of the pancreas |
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what surrounds the langerhans
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serous acini
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Mallory-Azan staining:
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Langerhans islet:
A (alpha) cells: red B (beta) cells: brownish orange D (delta) cells: blue |
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Immunohistochemistry:
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staining will be black or brown
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silver stain stains ?
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A cells , in the periphery of acini
electron microscopy --- dense core granules stain differelt ***** |
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A cells
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red in mallory azan
most are in periphery ***** Dense core secretory granules (250 nm) surrounded with light substance Secrete mainly glucagon gastrin also secreted here ***** |
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a cell also stained by ..
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Grimelius silver stain
from A cells.... Zollinger-Ellison syndrome: Gastrin-producing pancreatic tumors (developing probably from A cells) results in excessive acid secretion of the stomach. Ulceration may develop. |
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B cells : color ?
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brown , orange , in the center ...
have dense core granules that secrete insulin *** |
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D cells ?
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periphery
blue !!!! huge , low density sec granules ****secrete somatostatin |
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pale cells
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cant really see
5% of volume subtypes : F cell: secretes pancreatic polypeptide (PP) D-1 cell: secretes vasoactive intestinal peptide (VIP) ***** EC cell: secretes substance P (SP), secretin, motilin |
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Parasympathetic (cholinergic) stimulation:
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Increases glucagon secretion
Increases insulin secretion |
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Sympathetic (adrenergic) stimulation:
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Increases glucagon secretion
Inhibits insulin secretion |
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circulation ... ?
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Prob a mixture of both
From cortex into core --- B cells receives blood from both A and D |
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circulation 2 ?
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(Conclusion: The inhibitory effect of insulin on the glucagon secretion is carried out by the insulin in the general circulation)
kind of like a portal system .. ? |
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Langerhans islet: actions of the major hormones
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Gluc stimulates insulin
Insulin inhibits gluc Somatostatin ---- inhibits both |
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glucose sensitivity
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Brain first tissue affected with hypoglcemic
Headache , unconscious Rbcs wount die Glucagon will signal low glucose levels |
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danger zone
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40-60
headache women will faint with low sugars |
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other signals :
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Other signals: neural in origin
Cortisol and catecholamines – raise glucose ******* Diff Mm – breakdown of protein , AA for gluconeogeneis Catechols hit same receptors |
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glucose levels ..
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mM have to do a conversion – 90 is 5 mM
Below 90 is low Above 90 is high Post meal – a little glucose inc |
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normal glu levels
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Normal between 80 and 100 mg/dL
mg/dL and mg% are the same 90 mg/dL = 5 mM glucose |
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symptom of hyperglycemia caused by diabetes
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spilling fo glucose into urine
good screening test .. |
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*******conversion formula for gluocse *** on exam
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mM glucose x 18 = mg/dL glucose
mg/dL / 18 = mM glucose |
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low sugars
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affect neural
Headache, seizure, coma, death |
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high sugars
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multifactorial
Fluid imbalance **Nonenzymatic glycation of proteins-slowly with time Excess production of polyols--- to sorbitol - strong osmotic effect |
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Nonenzymatic Glycosylation***
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time and conc of glucose
more glucose , more of this rxn tissues that are long lived , affected most -- such as hemoglobin -lifespan is months measure the amount of glycosylated hemoglobin |
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HBA1c levels..
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HBA1c normally constitutes about 4% of hemoglobin in the red blood cells.
above 8% - twice as much a patient that is non-complaint... |
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advanced glycosylation products or AGEs
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keep glu levels low!!!!
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body has to make fructose --- esp men !!!! sperm
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Polyol Pathways
converts sugars to polyalcohols - makes sorbitol |
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used to say microvascular complications (retinopathy, nephropathy, neuropathy) to the polyol pathway
and macrovascular complications (stroke, gangrene, myocardial infarction) to noenzymatic glycation and AGEs. |
both pathways contribute to both sets of complications.
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glucagon levels.....
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remains flat !!! b/c down with carbs , up with proteins.. think of it as a ratio with insulin..
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insulin .. and target
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What kind of hormone..
Tells you singlaing.. !!!! Olypeptode hormone is water soluble Has to act as surface……….. Can’t get across memebrane |
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insulin syn
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one long polypeptide with 4 cleavages
hormone consists of 2 chains linkedby bridges and a C - peptide ****** |
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C peptide
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Secretory protein
Sy by being sent to rough ER Singal peptide targets them there What enzyme ? Trans golgi network – packaed into secretory vessicle Within a secretory vessicle --- Ratio of C peptide is one to one ********* |
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Munchuasen
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hurt yourself to get sympathy
by proxy: gets attention if child sick , so will hurt kid |
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injecting yourself with insulin for poison
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Should always be about as much C peptide
If injecting .. There will not be C peptide … Insulin would be higher |
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Insulin secretion
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preformed insulin waiting to go
dense structure |
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how does in in glucose cause a release ?
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ATP levels
liver and pancreas .. respond GLUT2-impossible to saturate has glucokinase.. hard to saturate.. level of act inc prop to level of glucose ATP affects K channel change in K influx, inc K levels so you get a depolarization Ca influx that cuases insulin granules to fuse with membrane |
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Mechanism of insulin secretion
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stimulated by glucose influx (>80 mg/dL)
glucose enters pancreatic cells via the GLUT2 transporter glucose metabolism increases ATP levels ATP-dependent K+ channel closes pancreatic cell membrane depolarizes voltage gated Ca2+ channel opens allowing intracellular [Ca2+] to rise secretory vesicles containing insulin fuse with plasma membrane |
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Insulin mechanism of action
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Insulin binds a specific insulin receptor (many tissues)
Insulin receptor is an α22 heterotetramer Insulin receptor belongs to a large family of Tyr-kinase receptors Insulin binding induces receptor Tyr-kinase activity phos tyrosine residue --- hydroxyl group gets phos |
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IRS protein
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bound to TK
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most impt action of insulin
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induces protein trafficking (example: GLUT4 to plasma membrane)
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also a cell growth receptor ****
cell mitgenesis and growth regulating genes Mm -pathway ************ |
1. PI3-kinase - Protein kinase B pathway
Regulates enzymes that control metabolism Glycolysis, gluconeogenesis, glycogen synthesis, fatty acid synthesis Stimulates GLUT4 transporters moving to plasma membrane |
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other pathway
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MAP kinase pathway
Stimulates gene expression Stimulates mitogenesis |
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PI3 pathway - aka prot kinase B path
enzymne as AKT *********** |
inc protein trafficing - Glut 4
and major enzymne control |
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MAP kinase -- mitogene
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turns on gene expressionand cell growth and mitosis
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PI3 kinase more... see pics !!!!!!!
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IRS gets phos
this activates PI3 mem bound phospholipid -- putting on another phos *** still attached to membrane (this is diff from path where is released with Ca release) can activate PDK-1 and PK-B , PK-B detaches from membrane .. and is soluble, can stim all sorts of pathways |
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Insulin stimulation of glycogen synthesis via PI3 kinase
fed state |
Insulin signals , and activates PK-B
Glycogen syn on Glycogen breakdown off Look at GSK-3 , turns from active to inactive In making inactive --- enzymne gets de-phos --- and turned on ***** In this case , we stim a dephos , even though … Confusing 18 Realize : allof these pathways.. Glycolysis , all controlled by insulin .. All affected by PK-B |
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MAP kinase
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Ras-- G protein is 1
raf -- is 2 - a kinase Mek then Erk these are the targets fro drugs being used in 10 years*********** learn them |
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glucagon
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G protein regulated (trimeric )
GTP bound -- it dissociated and alpha subunit , and alpha -- stimulates Adylate cyclase.. get a cAMP--stim protein kiase A to actie form insulin is a prot kinase B **** |
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where does glucagon act ?
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liver and kidney ..
no where else ******* get it straight glucagon - shuts things down , dont want to do that inother tissues.. just cuz we haven't been fed... skeletal muscle stop glycogen breakdown ? no |
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Type I - Insulin-dependent diabetes mellitus (IDDM)
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deficiency of insulin production
destruction of insulin producing cells in the pancreas often an autoimmune disease usually early onset (children or teens) Tx : insulin |
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Type II - Noninsulin-dependent diabetes mellitus (NIDDM
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signaling cascade prob
insulin wont work , not always true though .. during end... panncreas fails sometimes.. also give insulin is a resistance to insulin action insulin levels may be normal usually later onset linked to genetics and obesity |
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MODY 2 (maturity onset diabetes of the young)
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defect in pancreatic glucokinase
Insulin secretion requires ↑ [glucose] to cause ↑ [ATP] Therefore insulin release only at very high [glucose] in these patients no glucokinase present .. dont get ic in ATP though !!! like they r nnot making insulin |
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DM
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transporter that up to tissue ..
Glucose is overproduced and under-utilized causes polyuria and polydipsia |
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DM
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disorders in fat Metab
unregulated... will go into DKA |
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Levels of circulating glucose, ketone bodies, fatty acids, and VLDLs increase
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Ketosis may occur in unregulated IDDM
Fatty acids are released by the adipose tissue VLDLs and chylomicrons are poorly metabolized because lipoprotein lipase synthesis is signaled by insulin |
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Glucagon-Like” Peptide 1 (GLP-1)
an incretin hormone |
Released by luminal glucose, fats and amino acids in the duodenum & jejunum
Arguably the most important incretin hormone Releases preformed insulin (cAMP/PKA pathway) but suppresses glucagon |
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reflexes
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thinking about food, and become hypoglycemic..
Cephalic Reflex: triggered by thought, sight, smell and taste of food. |
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other reflexes..
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Enteropancreatic Reflex:
Triggered by sugars and amino acids (probably osmolarity) in the small intestine. Neurotransmitter Acetylcholine released at the cells acts through phospholipase c & DAG/IP3/PKC to release preformed insulin. |
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incretin hormones
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all release insulin
all induce satierty *****enhances insulin response |
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C protein
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co -secreted with insulin
half life of 19 hours insulin 20 mintes - acute measure C peptide to see insulin levels ******** |
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Amylin
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Amylin is co-secreted with insulin******
Encoded by a separate gene Decreases food intake and gastric emptying Amylin analog used in therapy Excesses in NIDDM can cause fibrosis |
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peptide hormones..
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all today ..
give IV |
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glucagon ****************
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Glucagon inc fat utilization
dec hepatic formation & export of triglycerides inc cellular uptake of LDL inc. adipocyte hormone-sensitive lipase |
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pH less than 7
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acidotic coma
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Weakness, tremor, pallor, sweating, fainting
Coma ensues near 40 mg/dL |
Hypoglycemia
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NIDDM
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metabolic syndrome related
Coincident hypertension & hyperlipidemia, often diagnosed before NIDDM, suggests an underlying earlier cause. most look like , metabolic syn |
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diagnosis criteria for diabetes
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Random glucose concentration greater than 200 mg/dL with classic signs and symptoms
Fasting glucose concentration greater than 126 mg/dL on more than one occasion Abnormal oral glucose tolerance test (OGTT) |
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type-I diabetes pathoophys
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Autoimmune process started before clinical signs/symptoms are present
Progressive loss of insulin reserves over time Classic manifestations of the disease |
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type-II diabetes
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Prototypic multifactorial complex disease
Environmental factors (sedentary life style and dietary habits) Genetic factors |
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diabetes complications
Macrovascular disease |
Lesions involving both large- and medium-sized muscular arteries
Causes accelerated atherosclerosis Increased risk of myocardial infarction, stroke, and lower extremity gangrene |
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******Diabetic retinopathy, nephropathy, and neuropathy
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Microvascular disease
Capillary dysfunction in target organs Retina, kidneys, and peripheral nerves neuropathy--- feeling not as good |
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Glycemic control
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Ameliorates the long-term complications of diabetes
Percentage of glycosylated hemoglobin (HbA1C) honesty---- do a A1C --- anything greater than 7% , not well controlled... |
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Diabetic Microangiopathy
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kidney
diffuse thickening of basement membrane |
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PAS stain
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targets BM of kidney
thickened in diabetics.. |
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Diffuse mesangial sclerosis
***** |
Diffuse increase in mesangial matrix
Mild proliferation of mesangial cells with ****increased thickening of GBM Correlates well with ***increasing proteinuria (decreasing renal function) |
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Nodular glomerulosclerosis
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Kimmelstiel-Wilson disease
Ovoid or spherical, laminated, nodules of matrix |
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Hyaline arteriolosclerosis
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not pathoneumonic for DM
but happens often |
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polyuria, polydipsia, polyphagia
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type I diabetes
500 to 700 mg/dL |
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Macrovascular complications
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Most common causes of mortality in long-standing diabetes
Myocardial infarction Renal vascular insufficiency Cerebrovascular accidents |
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Microalbuminuria*****
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Low amounts of albumin in the urine
>30 mg/day, but <300 mg/day Marker for greatly increased cardiovascular morbidity and mortality |
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neuropthay with diabetes
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Glove and stocking" pattern of polyneuropathy
lower extremitieis |
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gastrinoma
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ZE syndrome
diarrhea |
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necrolytic migratory erythema *****
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bad pic
alpha cell tumor - super rare, but BOARDS LOVES RARE |
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insulin for hyperkalemia
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glucokinase phos glucose
besides sugar , K gets sucked into cell with it ** review glycolysis , but this is a key point, K sucked in with glucose kidney secretes K , if it fails will build up |
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pills for diabetic
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type II only
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treat hyperkalemia *****
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give sugar and insulin
if dont give sugar , then will get hypoglycemia |
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c peptide levy
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Distinguish insulinoma btw abuse
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action of insulin
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turns on LPL -- so fats can be broken down and taken into cell
LPL hydrolyzes triglyceride in blood so free fatty acids can enter adipose cell |
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what about fat inside the cell ?
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inhibit !!!!
HSL hydrolyzes triglyceride in adipose cell to break down fat and release ffa into blood |
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what else does insulin do ?
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Stimulates glycogenesis
Suppresses gluconeogenesis (b/c lots of glucose already there !!!) Stimulates protein synthesis |
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history
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Almost identical … except these positions
Principal : when a molecule is costant from one species to the next Called homology Tells us , mothher nature recognized the value through evolution and did not fiddle with it |
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types of insulin
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regular-short acting
take with meals rapid onset, peaks quickly |
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general principle pharm *******
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things that act quickly , leave quickly
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Lispro
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act 5-15 min !!!!
regular is 30-60 !!! lispro --peaks faster and leaves sooner taken very close to a meal ***** advantage -- no planning ahead |
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NPH insulin (look at dose response curve)
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slower acting
used in combination to tx diabetes 1-2 hour onset *****all of these used together to mimic phys action of the pancreas |
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Glargine
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long acting insulin
***no peak !!!!! smooth onset plateua |
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which is closer to normal phys ?
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glargine -- low level throughout the day , just like insulin in body
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conventional vs. intensive insulin therapy
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intensive -- long acting , 3 doses of regular or lispro --better way , but more intense
conventional -- 1-2 injections --see objectives |
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insulin pump
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continuous subQ infusion
acts close to panncreas.. low basal secretion throughout the day **** with a little bolus @ meals .. bolus ( all at once) |
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Somogyi phenomenon*****
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pt : hypoglycemic when sleeping , so the body.... coutnerreg hormones kick in , and sugar high in the mornin g..
if you think this is what is going on ... dec the insulin that taking lesson: dont just inc insulin b/c sugars are high |
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honeymoon phase *****
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tell people about it
dx with diabetes , pacreas regains .. secretory capacity -- like a last horeau --- so , insulin requirment goes down .. "do, guess what... my diabetes is gone " so, caution people about this ...!!!!!!! |
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adverse effect
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hypoglycemia-if u take too much !!!
weight gain ... calories , put to use---caution them lypodystrophy ---- rotate injection sites , this will catch up with you .. eventually , hit same site again , fat will break down |
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Diabetes Control And Complications Trial (Dcct)
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proved intensive vs. conventional
intensive therapy worked better --- less complications microvascular comp-- kidney , eye , nerve people complain , tell them this .. |
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classes of oral drugs
know main Mm of action |
Biguanides
Sulfonylureas Thiazolidinediones α Glucosidase Inhibitors |
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Biguanides
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Decrease glucose production
Metformin--dec hepatic glucose production - inc insulin sens -inc .. peripheral glucose uptake and utilization |
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DOC
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not really for a disease
for a patient not for heart failure or kidney failure ******** |
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metformin clinical efficacy
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effective
Metformin decrease HbA1c 1.5% Metformin decrease FBS 60-70 mg/dl Doesn’t produce hyperinsulinemia Doesn’t produce hypoglycemia |
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metformin adverse
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can causeB12 def
rarte: lactic acidosis 1/30K , but 50% mortality rate *********** iodinated contrast , so more kidney toxicity ***** |
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C I for metformin *******
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CHF and kidney failure
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Sulfonylureas are ********
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secretagogues
binds to islet cells and closes K channels , inc in intracelluar Ca exocytosis ... |
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typical sulfonureas
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Glipizide (glucotrol)
Glyburide (micronase) Glimepiride (amaryl) |
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sulfonureas clinical efficacy
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sulfonylureas decrease HbA1c 1.5%
sulfonylureas decrease FBS 60-70 mg/dl *******Equally effective as metformin |
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diet
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key
throw all the insulin you want at them , but if not good diet wasting time |
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sulfonureas
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can cause hypoglycemia
(unlike metformin ***) SIADH (ADH too high) --what is different ? aldosterone is salt , this is just free water ***** why impt ? heart failure , cirrosis (albumin gone) and renal failure... 3 with water retention ... |
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fluid overload with hyponatremia *********************************
aldosterone mediated |
cirrosis , nephrosis , cardosis
cnc |
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SIADH , also fluid overloaded , but..
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no swollen ankles.....no edema .. no sodium , it's just free water .. people manage this , does not leak out
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Thiazolidinediones
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inc insulin sensitivity and glu uptake
Rosiglitazone (Avandia) Pioglitazone (Actos) mono or combo therapy |
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Thiazolidinediones efficacy
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less effective
decrease FBS 20-50 mg/dl (not 60 or 70 ) decrease HbA1c 1 % (not 1.5 ) Rosiglitazone/pioglitazone equally effective |
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alk phos , what kind of enzymne
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canalicular enzymne
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Thiazolidinediones
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Adverse reactions-
Cardiac: exacerbates CHF Hepatic: check transaminases |
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α Glucosidase Inhibitors
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decreases digestion of ingested carbohydrates
inhibition of intestinal brush border enzymes. (hydrolyzes polysaccharides to glucose) |
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α Glucosidase Inhibitors
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inhibit absorption , so inhibit .. post-eating ..............
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Acarbose
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bad side effects
flatulence, diarrhea, abdominal pain -not used a whole lot ... |
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Non oral type II Rx: Exenatide
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Synthetic peptide (incretin mimetic)
**** these act like insulin .. inhibits glucagon secretion |
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Sitagliptin, Saxagliptin
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DPP is the enzyme which inactivates incretin.
↑ Incretin by inhibiting DPP double negative inhibts enzymen that degrades incretin ******** |
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United Kingdom Prospective Diabetes Study
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reduced risk of microvascular end points by 25%
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ACCORD study
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type II diabetics
standard vs. intensive one group under 6 , one under 7-8 tighter control --excess deaths--maybe blood sugars too low? excess deaths -not hypoglycemia ... |
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doe of poo
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Eastern philosphy – something to an extreme ---- becomes it’s opposite …
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diabetic in hospital
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having a heart attack , and controlling too well.. get hypoglycemia, and whatever they came in for , is worse
hypoglycemia -- make sthings worse |
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how does fiber help glycemic control ?
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Lentils –cheap to buy for good nutrition
Fiber slows digesnntion , so rapid inc in sugar not there |
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envirnmental stress superimposed on a genetic predisposition
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diabetes type 1
Islet cell Abs insulin abs islet cell mass shrinks |
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concordance rate of 30%
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Monozygotic twins --- means if one twin has it , the other twin has it
the higher the rate , more genetics involved. what about type II ? |
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concordance rate in type II ?
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90%
As time goes on , pancreas secretes less insulin Excess sugar production |
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metabolic syndrome
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low HDL, high LDL
htn obesity |
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education of patient ..
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Education: not good @ it –we are too smart
May be talking to people who are a 5th grade level How’s your polyuria today |
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how often to check sugars ?
teach monitoring ... |
5 times a day
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HbA1c
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less than 7
For us 6 If 6.5 --- keep a close eye.. If at 8-10-12… treat!!!!!!!!!!!!! |
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Midodrine
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alpha -1 agonist .
Why would ths help --- not so dizzy ….. Tickling of receptor .. |
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Treatment of Peripheral Sensory Neuropathy
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Amitriptyline
Gabapentin Pregabalin |
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Treatment of Gastroparesis
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Metoclopramide (reglan)
Cholinergic: improves ***gastric motility by stimulating release of ACh from myenteric plexus Dopamine antagonist (antiemetic) vagomimetic , stim release of Ach extrapyramidal, tardive -side effect ...dystonia .... clorpromazine ..... when we see this ...what do we do ? GET benedryl *********** |
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NPDR
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Hemorrages all over
Yellow – are exudates --- microinfarcts Can go blind He will get laser--- photocoagulation .. Fuses shut, so wont bleed NPDR--- non-prliferative diabetic retinopathy |
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PDR
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Eyes grows new ones.. b/c old ones are bad
This is neovascularization Proliferative diabetic retinopathy Vaso vasorum ----- little vessels that feed large vessels Vaso nervorum – for nerves Diabetic neuropathy – is a problem with just that |
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Viagra
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Dephosphorylation of myosin light chain--no contraction , relaxes
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cAMP in heart failure ?
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Milrinone , amrinone ....
phopho-diesterase --- act on cAMP, dont cause vasodilation .. they are ionotropes ... inc muscle contraction .... differ from cGMP !!!!!!!!!!!!!!! |
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how could one contract and one relax ?
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by working on cAMP , inc intracellular calcium ***********
tropomyosin ... and troponin C --- and Ca binds .. |
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nephropathy , tx
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Ace-i
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other complications of DM
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prone to infections
Increased Incidence of Infections E. coli (UTI) Candida (vaginitis) Pseudomonas swimmer's ear (otits externa) TB (lung) Post op wound (staph- skin) |
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swimmers eye
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adenovirus
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foot ulcers
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step on a tack - ouch
diabetic with peripheral neuropathy -- wont feel IV /PO AB debribe wound gangrene , osteomylitis |
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PE
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foot problems ? look!!!!! they wont feel
microalbuminuria --- once seen -- put them on Ace-i |
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Gestational DM
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4% of pregnancies
2nd or 3rd trimester Most resolve postpartum ****50% long term risk of DM later in life high birth weight |
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high birth weight *****
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glucose crosses placenta
insulin does not baby responds with own insulin and baby grows |
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hyperosmolar non-ketotic syn
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a complication of type II diabetes
*****very high blood sugars ---- about 1000 polyuria , rampant , can become obtunded .. change in mental status *****no ketosis just a little insulin from coming out of pancreas to prevent acidosis .. |
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hyperosmolar non-ketotic syn cause ************
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infection
uti, pneumonia, cellulitis |
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hyperosmolar non-ketotic syn cause
tx |
fluids!!!!!! they have been peeing a lot
need insulin , but volume most impt |
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MODY
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gene mutation
kind of in between type I and type II AD disorder... Age 10-25 Impaired insulin secretion |
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hypoglycemia
skip breakfast... |
Mild (BG: 55-70 mg/dl) Irritability, palpitations, tremulousness
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hypoglycemia
moderate |
Moderate (BG: 40-55 mg/dl) Blurred vision, confusion, lethargy
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severe hypoglycemia
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Severe (BG: 40 mg/dl and below) Coma, *****seizures, death
seizure meds dont work *** seizing -- check sugars!!!!!!!!!!!!!!! |
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Causes of Hypoglycemia
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Insulin reaction
Reactive Factitious Insulinoma Addison’s Disease |
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Addison's
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Ad- for adrenal
hypoadreneal Cushings - opposite |
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glucagon phys
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homeostasis
cant let insulin lower sugars too much |
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DKA
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Aceta-acetate, acetone, beta-hydrybutrate
In the body, ketones act like acids elevated anion gap- caused by ? |
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MUD-PILES
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sodium- sum of bicarb and clhoride
8-12 is normal |
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faty acid oxidation
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CHO's first
then fatty acids - chylo's , liver |
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when are ketone bodies formed ?
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when fats burn to excess
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ketone body equilibrium
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acid plus AA yileds beta-hydroxy-butyrate
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DKA--signs and symtomps
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Kussmauls
deep rapid brethes to blow off CO2 acidoitc from the diabetes comp is resp alkalosis -- must blow off CO2 *********** other's on slide ... |
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DKA -- sugar ?
IV volume bicarb ? pCO2 |
high ..
low low low pH is HCO3 /PO2 Maintains a constant ratio************* bicarb down , CO2 down |
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ph ?
anion gap ? sodium changes |
down
inc first it goes downm then it goes up..**** |
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Potassium
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high then low as you treat it ...
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luck favors the prepared
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louis pasteur
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Hyponatremia/Hypernatremia*****
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Sodium falls 1.6 meq/l for every 100 mg/dl that glucose goes up
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sugar of 500
sodium ? |
128-129 ish
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tubules
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sucking fluid out of cells, and in tubules.. glucose pulls water out .. so , sodium comes back up ******
tricky tricky Cellular dehydration followed by . . . Intravascular Volume depletion |
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suagr of 500, sodium is 137 , what of intravascular voulme ?
*********************************** |
sodium should have dropped
b/c it is normal , peed it out high blood sugar with a normalish sodium ....... bad news *********** recognize it |
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not taking insulin, leads to DKA
what else causes ? |
infection , meningits.. cellulitis
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TX for DKA
dehydrated |
IV fluids NS
IV fluids NS IV fluids NS ( then D5W /.45 NS ) use regular or short acting .. |
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IV fluids NS ( then D5W /.45 NS )
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to prevent hypoglycemia
why is there a danger ? treating sugar, acidosis , lytes --- sugar down first have to be able to resolve the acidosis , so have to keep giving insulin, therefore... have to give a little sugar so ,dont get hypoglycemic ********** |
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give Bicarb when ?
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pH is less than 7
why ? it can havea rebound effect or become alkylotic |
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how to measure ketone boides..
LABS*********** be a hero ..... |
The standard urine test and some serum tests for ketones (nitroprusside reaction)***** measure acetoacetate
if you forgot your biochem --- keep checking acetone level..... small, moderate, low.... acidotic.. a lot of the betahydroxybut ketones ... getting higher.... forgot their biochem ************ lab testing .... testing for compound that inc as people get better.... |
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Krebs cycle and the grill
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Krebs---- sugars , and acetyl CoA from fats…..
Why ATP important ……….. Grill--- fat burned – unregulated energy releaes Krebs – does this , but stores it ………… |
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embryological source for the thyroid
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thryoglossal duct from the tongue
C cells from Ultimo-pharyngeal body btw fourth and sixth poutch |
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C cells origin ?
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neural crest
p.72 |
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location of thyroglossal duct cysts ?
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midline
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Neural Crest
Neural crest cells are important for the development of the pharyngeal arches. Facial defects, resulting from deficient neural crest cells, are also accompanied by what other defects? |
defects?
75 a. Treacher Collins Syndrome • genetic defect involving the first arch • variable; may have any of the following: hypoplasia of the mandible, face; malformation of ears, eyelid defects, and faulty dentition b. Pierre Robin Sequence • involves fist arch • micrognathia • cleft palate • external ear defects c. DiGeorge Anomaly – Involves abnormalities of the heart, parathyroid gland, face, and thymus gland (the degree to which the immune system is affected varies). Affected individuals will have congenital heart disease, unusual facial features with low-set ears, a small jawbone that recedes, wide-set eyes and are born without parathyroid glands. |
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238. Only muscle to abduct vocal cords
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Posterior cricoarytenoid
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239. Innervation of cricothyroid
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External laryngeal nerve
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240. Innervation of laryngeal muscles exclusive of cricothyroid
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Recurrent laryngeal
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237. Structures that pierce thyrohyoid membrane
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Internal laryngeal nerve,
superior laryngeal artery |
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Thyroid
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slightly larger in females; size various with cycles
located at the level of CV5-7 associated with the larynx and trachea invested in pretracheal fascia has a CT capsule contacts the carotid sheath |
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thyroid blood supply
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superior thyroid artery from external carotid
inferior thyroid from thyrocervical trunk veins: superior and middle thyroid vein drain into internal jugular inferior thyroid vein , drain into left brachiocephalic |
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major lymph nodes
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Jugulo-digastric
Jugulo-omohyoid |
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blood vessel and nerves**********
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inferior thyroid artery runs with recurrent laryngeal
(innervates all muscles here except cricothyroid***) superior thyroid artery runs with superior laryngeal nerve (FROM VAGUS***) internal branch to larynx |
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blood supply to parathyroids
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inferior thyroid artery
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follicle has colloid
follicle surrounded by clear cytoplasm C cells *********** what does the follicle contain ? |
thyroglobulin (inactive storage form )
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other name for C cells and what do they secrete ?
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parafolliclur cells
calcitonin !! |
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2 types of endocrine glands
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1. follicle
2. cord and clump |
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parathyroid has 2 types of cells , what ?
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principle and oxyphil ( more abundant with age)
principle cells arise from endoderm ********* |
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Thyroglobulin (TG)
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found in colloid
not TBG |
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Thyroidal I- Pump
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Stimulated by TSH and a certain antibody ??
graves - antibody |
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enzymne that is responsible for oxidation phase of thyroid hormone production *******
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thyro---peroxidase enzymne ****
inhibited by the drug Propylthiouracil (PTU) ****agranulocytosis , hepatitis |
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next stage is organification ... by what enzymne ?
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Thyroperoxidase
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DIT + DIT = T4
MIT + DIT = T3 what enzymne ? |
Thyroperoxidase- again
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steps in thyroid synthesis driven TSH ?
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uptake pump and hydrolysis
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Hydrolysis of Thyroglobulin
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TSH ↑TG uptake by the cells
TG hydolysis releases T3 & T4 MIT & DIT, I+ recycled. |
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how is thyroid hormone transported ?
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Albumin
Thyroxine-binding prealbumin ******Thyroid-binding globulin (TBG) < 1% free and active |
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Thyroid-binding globulin (TBG)
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**********
binds T3 & T4 pregnancy and estrogen therapy increase TBG levels, increasing total, not free levels of T4 |
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more TBG made , from estrogen ....
results ? |
More TBG around – more free hormone it will scoop up
Pituitary senses.. Free hormone level dropped , and more TSH put out Keep free levels constant Goljan: inc TBG, inc total serum T4 , not free ********** |
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pump inhibiting drugs
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99mTc pertechnetate- radioisotope used in thyroid scans (diagnostic)
Compete with I- at pump-concentrated by the thyroid |
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Wolff-Chaikoff Effect
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negative feedback like
excess iodine inhibits organification inhibts pump also normally self limiting |
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Organification Inhibiting Drugs
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SSKI- inhibits organification- Wolff-Chaikoff effect
Thiourea drugs supersaturated solution of potassium iodide .... |
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Biological Effects of T3
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Adipose tissue
GI Liver Muscle |
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4 B's for T 3 ******
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brain , bone, beta adrenergic tickling , and BMR
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bio effect more... *********
notice liver... |
Adipocytes- increases lipolysis
Intestine- increases glucose absorption Liver- increases gluconeogenesis, glycogenolysis, and LDL receptor synthesis Muscle- increases glucose uptake, protein synthesis, augments growth hormone effects |
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why the inc body temp , etc. ***
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T3 increases ATP synthesis and ATP utilization, both generate heat
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Cretinism
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Dwarfism
severe mental retardation not apparent at birth cured with oral thyroid hormone therapy why not apparent at birth ? b/c has “borrowed some from mom” lasts for 100 days |
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Myxedema
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swelling of facial tissues
dry hair and skin slow heart rate, low body temperature dull brain function cured with oral thyroid therapy |
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Pendred syndrome
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Hypothyroidism and sensorineural deafness
Caused by mutations in the SLC26A4 gene Complete absence of thyroid (thyroid agenesis) Thyroid hypoplasia |
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Autoimmune Hypothyroidism
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Circulating autoantibodies
Anti-microsomal Anti-thyroid peroxidase Anti-thyroglobulin antibodies |
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Secondary Hypothyroidism
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Caused by deficiency of TSH
Causes for hypopituitarism Pituitary tumor Postpartum pituitary necrosis Trauma Nonpituitary tumors Hypothalamic damage Tumors, trauma, radiation therapy |
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Hashimoto Thyroiditis
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Can occur in children
Major cause of nonendemic goiter capsule intact.... "well circumscribed" |
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Subacute Lymphocytic Thyroiditis
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not sub acute thyroiditis !!!!!!!!!!!
this one is painelss!!! Variant of Hashimoto thyroiditis Majority of patients have circulating anti-thyroid peroxidase antibodies |
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Graves triad ***
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Hyperthyroidism
Infiltrative ophthalmopathy with resultant exophthalmos Localized, infiltrative dermopathy Pretibial myxedema lack fibrovascular core |
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fibrovascular cores*************
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graves -
papillary carcinoma + |
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scalloped margins
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davey jones locker
gravs |
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Sporadic Goiter
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Female preponderance
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Multinodular Goiter
mistaken for ? |
More frequently mistaken for neoplastic involvement
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History of radiation treatment
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Associated with an increased incidence of thyroid malignancy
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Hallmark of all follicular adenomas
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Presence of an intact, well-formed capsule encircling the tumor
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benign neoplasm of thyroid
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Follicular adenomas
benigns outnumber carcinoomas 10:1 |
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nodules
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solitary : more likely to be neoplastic than multiple
younger : more likely neoplastic males : also more likely **** (exception to rule ) |
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neoplams of thyroid
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hx of radiation
hot nodules A LOT more likely to be benign |
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adenoma , from ?
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follicular epithelium
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hallmark of follicular adenomas ..
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presence of itanct .. well formed capsule
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thyroid carcinoma
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uncommon in US
female predominance |
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antibodies in graves disease
**** stimulatory !!!!!!!!!!1 |
Thyroperoxidase Abs
Thyroglobulin Abs |
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Tx for graves
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antithyroid drugs
PTU and Methimazole |
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Agranulocytosis *******
what to do ? from ? |
from PTU !!!
order a stat cbc with graves patient that is sick fever/sore throat ************ |
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other graves tx ?
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I 131
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thyroiditis antibodies
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TSH-R Ab , block
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managment for nodules
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FNA fine needle aspirate
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GI symptoms with thyroid ***
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kind of backwards with symp/parasymp
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Clinically.. T4 drops a little bit… pit senses… rises.. It brings T4 back to normal .. Never really see the drop b/c pituitary kicked in quickly
Goes on long enough to see an elevated TSH in the face of a normal T4 – first sign of |
hypothyroidism
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Tc99 pertechnetate*****
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used for thyroid scan
to ID hot or cold nodules competes with iodine @ the pump not same as I 131 (RAIU) which measures the function of the ENTIRE gland |
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thyroiditis vs. graves with thyroid scans *****
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in thyroiditis the gland is burnt out
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most impt known stimulus of the thyroid gland ?
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temp **
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secondary hyperthyroidism
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inc TSH , and T3/T4
dec TRH **** |
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tertiary hyperthyroidism
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everything up
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thyroid storm
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Rarely, a period of very high thyroid secretion can occur in hyperthyroid patients or patients with thyroid infections. This occurs when the follicular cells are damaged and may reflect massive release of stored follicular thyroid hormones.
****This will produce extreme hyperthermia, hypoglycemia, and possibly 'high output' heart failure leading to shock. A thyroid storm lasts about 3 days. |
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hyperthyroid goiter
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will be from secondary or tertiary hyperthyroidism
inc TSH |
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what thyroid disorder can cause athlerosclerosis ?
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hypothyroidism
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