Flashcards in endo DIT Deck (234):
cAMP modifying hormones (11)
IP3 modifying hormones(4)
Tyrosine kinase receptor modulators
insulin like growth factor
Platelet derived growth factor
fibroblast growth factor
cGMP modulators (2)
Preganancy leads to an increase of what liver product that may affect hormone affects
binding globulin decreasing the amount of free active hormone
Thyroid - TGH for example
Steroid receptor modulated hormone (5)
estrogen, progesteron, testosterone
Availabilty of binding hormone affects 2 things
amount of free hormone
activity of steroid hormone
increased sex binding hormone may have what affect on men?
gynectomastia due to decreased free testosterone
decreased sex binding hormone in women may have what effect in women?
ACTH and MSH are synthesized by what precursor?
Leads to hyperpigmentation w/ primary adrenal insufficency
Hyperprolactenima due to? (4)
pregnancy/ nipple stim
dopamine antagonists ) haloperidol, risperidone, domperidone, metoclopramide, methydopa
Symptoms of hyperprolactinemia in
pre meno women
hypogonadism -> infertility, oligo/amennorhea, rarely galatorrhea
post meno - asymptomatic, maybe galactorrea
Men - (low testosterone)low labido, impotence, infertility, gynectomastia, rarely galactorrhea
remember, prolactin inhibits FSH and LH
Clinical uses of octreotide(3)
-acromegaly, thyrotropinoma, ACTH secreting hormones
GI endocrine excess
-Zollinger ellison syndrome, carcinoid, VIPoma, glucagona, insulinoma
Need to reduce splanchnic circulation
-portal HTN, bleeding peptic ulcers
infertility, galactorrhea and bitemporal hemanopsia
inability to breastfeed, amenorrhea, cold intolerance
Which hormones share a common alpha subunit(4)
anterior pituitary is derived from
posterior pituitary is derived from
ADH is stimulated w/ ?(3)
high serum osmolarity
low volume contraction
atrial naturetic factor
low serum osmolarity
Oxytocin important w/
pregnancy and breast feeding
uterine contraction ( return to normal size/clamp bleeding)
inhibited w/ alcohol and stress
inhibit feeds back and blocks
progesterone and testosterone feedback on
ACTH is stimulated to release w/(2)
CRH from the hypothalamus
TSH is released from?
TSH from the pituitary
inhibited by T3 and T4 levels
Stimulated by TRH from hypothalamus
Prolactin leads to inhibition of ?
Prolactin stimulated by?
ovulation via blocking of LH and FSH
- stimulates milk production and breast development
stimulated to release by TRH and less Dopamine inhibition
GH effects (4)
decreases glucose uptake (insulin resistent- mobilize gluc)
increase protein synth
increase organ size and lean body mass
upstream control of GH (2)
other regulators of release(environmental)
GHRH - releases
+: exercise, sleep, hypoglycemia, puberty, estrogen, stress, endogenous opiods
-: obesity, hyperglycemia, pregnancy
Downstream response to increase of GH
increase of IGF 1
Rx for prolactinoma
Presentation of Acromegaly
coarse facial feature
impaired glucose tolerance
Diagnosis of acromegaly (2)
measure IGF1 - more stable vs pulsitile GH
failure of suppression of GH from the pituitary adenoma w/ glucose given
Zona glomerulosa secretes
Zona fasiculata secretes?
ACTH and CRH
Zona reticularis secretes?
ACTH and CRH
Adrenal tumor in adult vs kids
One key difference
Pheochromocytoma in adults -> episodic periods of hypertension
Neuroblastoma in kids -> maybe chronic HTN.
Symptoms of a pheochromocytoma (4)
HA, Sweats, Tachy, Eposodic HTN
Fetal adrenal gland is important in
secretion of cortisol for fetal lung maturation
responds to CRH and ACTH
ketoconazole acts to block what enzyme?
-conversion of cholesterol -> pregnenolone
ACTH acts on what enzyme to encourage hormone synthesis?
Angitension II acts on adrenal steroid synthesis by increasing the action of what enzyme
One thing in common w/ adrenal hyperplasia
all have decrease production of cortisol
-> ACTH ramps up
-> stimualtes adrenal cortex
-> adrenal hyperplasia
Enzyme responsible for converting testosterone to a more active enzyme
Blocked by what drug
5 alpha reductase
blocked by finasteride
estone, estradiol and estriol all need what enzyme to be made?
Features of 3 beta hydroxysteriod deficiency? (3)
Inability to produce
-androstenedione-> testosterone or estrone
Excessive Na excretion in the urine (salt wasting)
What features are characteristic in 17 alpha hydroxylase deficiency
inability to produce androgens/sex hormones and cortisol
-> phenotypic female that is unable to mature (no androstendione)
Hypertension w/ everything being shunted to aldosterone production
-Na and water retention
Desmolase is responsible for what
converting cholesterol to pregnenolone starting the adrenal steroid pathway
What features are characteristic of a deficiency in 21 alpha hydroxylase? (3)
Can't make cortisol or aldosterone ->
Hypotension and salt wasting w/ou Aldosterone
Masculinization w/ everything shunted to the right (androstenedione)
What features are characteristic of 11 beta hydroxylase deficiency?
Inability to produce Aldosterone and Cortisol
Increased production of 11 deoxycorticosterone
-Acts as a weak aldosterone -> HTN
masculinization with a shift to sex hormone production (androstenedione)
2 deficiencies characteristic in hypertension
11 beta hydroxylase
17 alpha hydroxylase
2 deficiencies characteristic in masculinization
11 beta hydroxylase
deficiency characteristic in hypotension
masculinization of feminization
Cortisol maintains BP how?
increasing alpha 1 receptors on the vasculature increasing sensitivity
Cortisol functions/effects on the body (5)
Maintain BP increasing alpha receptors on vasculature
Decreases bone formation
Anti inflam/immune suppresive
-neutropenia w/ adhesion disruption, inhibits prostaglandin production, block IL2
Insulin resistance (diabetogenic)
Gluconeogenesis/lipolysis and proteolysis ( increases enzyme expression)-> mobilizes sugars
Why is there a rise in WBC after giving a glucocorticoid
neutropenia transient due to mobilization of WBC stores in the vasculature
Regulation of cortisol 3 steps
CRH from the hypothalamus
-> Pituitary releasing ACTH
-> ACTH acts on the adrenal cortex (desmolase) to increase production of cortisol in the zona fasiculata
What can induce prolonged secretion of cortisol
Symptoms of Cushing Syndrome
Skin ∆s (striae, acne)
Necrosis of femoral head
4 Causes of Cushing Syndrome
Iatrogenic (exogenous steriods - #1)
Pituitary Adenoma - Cushings disease (ACTH)
Ectopic ACTH production - small cell
Adrenal adenoma (primary high cortisol)
Dexamethasone suppression test w/ high dose will suppress cortisol of which cause of cushing syndrome?
Suppreses pituitary adenoma
ACTH levels to differentiate between adrenal adenoma and small cell - both unsuppresed
-high ACTH in ectopic (small cell)
-low ACTH in adrenal adenoma
Presentation of HTN, hypokalemia and metabolic alkalosis due to
- Primary hyperaldosteronism
Have a low renin level
primary hyperaldosteronism name?
Triad of symptoms
- metabolic alkalosis
Rx for Conn syndrome (2)
epleronone and spironolactone
Secondary hyperaldosteronism due to: (4)
renal artery stenosis
chronic renal failure
hypo protein states (edema perceived fluid loss)
Going to have high renin levels (appropriately)
highly active synthetic mineral corticoid
Stimulation of Aldosterone
decreased aldosterone secretion
- low Na or volume
Addisons is most commonly due to
autoimmune attack of the adrenal cortex -> chronic primary adrenal insufficiency ( less aldosterone, cortisol)
--Less commonly: TB and METs
low aldosterone and cortisol ->
- weight loss
Primary adrenal insufficiency can be distinguished from secondary adrenal insufficiency by :
Increased amount of ACTH in primary adrenal insufficiency
Decreased in secondary adrenal insufficiency (problem is in the pituitary
Secondary adrenal insufficiency presents as?
less ACTH due disruption of the pituitary ->
NO skin pigmentation (no POMC)
NO hyperkalemia/hypotension (Aldosterone from renin)
How do you have hypotension w/ Addison's
chronic primary adrenal insufficiency
no alpha 1 upregulation w/ cortisol
No aldosterone leading to water and Na retention
Cause of acute adrenal insufficiency
adrenal hemorrhage w/ Nessieria meningitidia
(waterhouse frederichsen syndrome
Urine product detecting pheo?
Serum product looking for a pheo?
VMA ( vanilla mandelin acid) in urine
Normetanephrine and metanephrine in serum
catecholamine breakdown products
Pheos can be associated w which 3 tumor syndromes
Erythropoeitin can be secreted in 4 tumors
Renal cell carcinoma
Medical treatment for a pheochromocytoma?(3 steps
1st manage the BP w/ alpha 1 antagonist - phenoxybenzamine
2. maybe give a beta blocker
3. surgically remove the chromatin cell/adrenal medulla cancer
Rule of 10s w/ a pheochromocytoma (5)
90% adrenal - occasionally extra renal
90% do not calcify
most common tumor of the adrenal medulla in kids
test for urine?
tumor can be anywhere in the sympathetic chain 40% adrenal
less likely episodic HTN
homovanillic acid (dopamine breakdown) in urine
neuroblastoma is associated w. over expression of this oncgene
Histological stain to help differentiate
can stain for neurofilaments
Bombeison tumor marker associated w?
MEN 1 tumors
mutation in p53
Pancreatic tumors (VIPoma, gastrinoma, insulinoma, zollinger ellison, glucagonomas)
MEN 2a tumors
mutation in ret gene
PP's and M
Medullary thyroid carcinoma* (secretes calcitonin)
MEN 2 B tumors
mutation in ret gene
1P and 2 Ms
Medullary Thyroid Carcinoma
Mucosal neuromas (ganlioneuromatosis of the Gi and oral cavity)
MEN syndrome inheritence
all auto recessive
presentation of kidney stones or stomach ulcers w/ weigh loss
be concerned of what?
-parathyroid tumor -> PTH -> excess Ca
-Pancreatic tumor -> gastrinoma
most common cause of Conn syndrome
Thyroid is derived from what tissue in what location?
originates from the floor of the primitive and descends into the neck via the thyroglossal duct
foramen cecum is site of origination and most common site of ectopic thyroid tissue
anterior midline mass that moves with swallowing is what?
thyroglossal duct cyst that is due to persistent thyroglossal duct
Function of T3 and T4
ramps up metabolism
- bone growth (synergy w/ GH)
increase in beta 1 receptors of the heart
increased basal metabolic rate via increased Na/K atpase activity
increased glycogenolysis, gluconeogenesis. lipolysis
Thyroxine binding globulin increased w?
resulting lab values
Increased TBG in pregnancy and OCP use
- leads to increase in total T4 and T3 w/ binding of free hormone
-percieved depletion of free hormone leads to increase in release which is again bound up -> normal/elevated T3/T4
TSH can be low due to similarity to beta hCG
Enzyme responsible for oxidation and organification go iodide?
Iodide is brought into the follicular cell via?
Bound to what AA residue
then oxidized to Iodine and bound tyrosine AA residue on thyroglobulin (organification)
2 drugs to prevent thyroid hormone synthesis
Which is preferred overall?
Which is preferred in pregnancy
- blocks peripheral conversion of T4-> T3
-used in 1st trimester
-generally worse SFx profile w/ agranulocytosis, liver dysfunction
- preferred over all
- used in 2nd and 3rd trimester only due to risk aplastic cutis in 1st
Symptoms of hyperthyroidism
heat intolerance -> due to production/metabolism
pretibibial myxedema - graves
warm moist skin
Lab value used to screen for hyperthyroidism
TSH would be low
-very responsive to small changes in T3 and T4
brief episode of hyperthyroidism followed hypothyroidism, painful thyroid on palpitation?
entire episode was preceded by what event?
Usually preceded by a viral/ flue like illness
Rx for subacute thyroiditis?
see on histology?
NSAIDs for pain for it is usually self limiting
HLA B35 assoicated w/ this thyroid pathology
see on histology
Focal patches of hyper functioning follicular cells working independently of TSH due to mutation in TSH receptor
Reassurance on radioactive iodide uptake?
toxic multinodular goiter
increase release of T3 and T4 seen
Look for HOT nodules -> rarely malignant
Jod Basedow phenomenon
patients beocmes thyrotoxicosis after being given exogenous iodine (post CT w/ contrast or amiodarone) and patient has a thyroid deficiency goiter and goes crazy w/ now iodine
Graves disease presents as?
presents w/ hyperthyroidism, pretibial myxedema and exothalamos due to presence of TSH receptor location; and a diffuse goiter
due to autoimmune creation of thyroid STIMULATING (odd) immunoglobins (IgG) that act as TSH -> increase of T3 and T4 release
HLA DR3 and HLA B* are associated w/ what thyroid pathology
Thyroid storm is due to?
stress induced catecholamine surge leading to death by arrhythmia ( restless, fever, sweating, tachy, tremor, delirium, vomiting, change in mental status)
Complication of graves and other hyperthyroid disorders
Rx: beta blockers, propylthiouricil, methimazole
stroma ovarri teratoma
teratoma w/ functional thyroid tissue -> hyperthyroid presentation
recent injection using a IV contrast leads to presentation of hyperthyroidism
presents as hyperthyroidism post thyroidectomy or radio ablation of thyroid
given too much T3 and T4
graves disease TSH and T3/T4 levels
TSH is low, Thyrois stimulating immunoglobin (IgG) acting on thyroid ->
Body mostly makes what type of thyroid hormone
Stable 6-9 days. longer half life
histology of 3 main hypothyroid states
-lymphocyte infiltration, Hurthel cells
-fibrous w/ macrophage and eosinophil infiltration
Most common cause of hypothyroidism
See what in serum potentially?
thyroid peroxidase antibodies
increase risk of what CA w/ hashimotos?
Commonly associated w?
B cell lymphoma
other autoimmune pathologies: Addisons, DM, sjogrens
Transient hyperthyroid for a couple months, painless thyroid, eventually hypothyroid
HLA DR5 and HLA B5 are associated w?
Causes of congenital hypothyroidism(5)
defect in T4 formation
failure of descent
iodine deficient mother (most common world wide)
transfer of mother's auto-ab/medication across placenta
Presentation of congenital hypothyroidism (4)
dwarfism (lack of synergy w/GH)
Reidals thryroiditis presentation
thyroid replaced w/ fibrous tissue (fixed/ rock hard/ painless goiter)
concern w/ extension into local tissue and compression
Histology you see eosinophilia and macrophage infiltration
fixed, hard painless goiter
usually what is given once a day for hypothyroidism
not used as much as levothyroxine
Presentation of hypothyroidism
dry cool skin/brittle hair
hypothyroidism has what effect on lipid profile
increases LDL and total cholesterol
Papillary carcinoma prevelance and presentation (4)
empty appearing nuclei/orphan annie/ ground glass
activation of tyrosine kinase receptor
Thyroid cancer associated w/ activation of tyrosine kinase receptor(2)
Medullary thyroid carcinoma
Risk of papillary thyroid carcinoma increases w/ (2)
childhood radiation Rx
Gene mutation in Ret oncogene in which thyroid carcinoma?
Also associated? (2)
Papillary thyroid carcinoma
Most common mutation in the BRAF gene for thyroid carcinoma (serene/threonine kinase)
commonly associated thyroid cancer w/ either RAS or PAX8-PPAR mutation
cancer arising from the parafollicular C cells
Medullary thyroid cancer
Follicular carcinoma vs adenoma
whether or not the fibrous capsule has been pierced or not
Medullary carcinoma is located where?
parafollicular C cells
Associated w MEN2A and MEN 2B
Have a hard single fibrous nodule in an older patient be concern w?
undifferentiated/anaplastic carcinoma vs reidels in a younger patient
Sheets of cells in an amyloid stroma
medullary thyroid carcinoma
2 thyroid tumors associated w/ RET mutation
both tyrosine kinase activators as well
Thyroid tumor complications (2)
hypocalcemia due to parathyroid removal
hoarseness w/ damage of the recurrent laryngeal nerve
parafolliciluar cells secrete?
located the medullary of the thyroid
Associated w/ medullary thyroid carcinoma
Endocrine pancreas cell types and products (3)
Glucagon from the alpha cell
insulin from the beta cell
Somatostatin from the delta cell
Glut 2 transporter found where(4) and responsible for
pancreatic beta cells
responsible for glucose sensitivity,
Glut 4 transporter found where(2) and responsible for
Responsible for insulin sensitive take-up of glucose
GLUT 1 transporter found where? (2) responsible for
RBCs and the brain
responsible for insulin independent take of glucose
Insulin receptor is what what type
tyrosine kinase leading to increase of GLUT 4 taken in
How is insulin released from the beta pancreatic cell (6 steps)
increase in glucose -> Glut 2
-> aerobic glycolysis -> increase of ATP/ADP ratio
-> closing of ATP sensitive K cells
-> depolarization of cell membrane
-> opening of Voltage gated Ca channels and influx
-> vesicles containing insulin fusing and leaving
Results anabolic effects of insulin (4)
increase of glucose transport in skeletal muscle
increase in glycogen synthesis
increase in triglyceride synthesis
increase in protein synthesis
Results of glucagon catabolism(4)
-> ketone body production
mobilize stored energy and eventually increases insulin secretion
Presentation of DM (5)
polyphagia w/ weight loss (unable to get sugar in)
2 main pathologies of Diabetes
-small vessel disease: retinopathy and nephropathy
- large vessel disease: atherosclerosis, gangrene
Protective drug w/ nephropathy
Nonenzymatice glycosylation in DM leads to (3)
Small vessel disease
- hemmorage, exudates, microneurysms(flame)
-nodular sclerosis (kimmerstiel wilson nodules)
Large vessel disease
Osmotic damage in DM is due to presence of what enzyme and lack of another in what organs (4)
have in aldose reductase, glucose -> sorbitol
Deficient in sorbitol dehydrogenase
Not in Retina, lens, schwann cells, kidney
HLA DR3 -DQ2 and HLA DR4 DQ 8 are associated w/
DM type 1
Which DM has a strong hereditary predisposition?
DM type II
DKA is associated w/ what DM?
Hyperosmolar hyperglycemic state is associated w/ what DM?
Auto antibodies against GAD?
DM type I
What are some common causes of DKA?(7)
Infection- pneumonia, gastroenteritis, UTI
diabetic med reduction/omission
severe medical illness - MIC/CVA/truma
all mobilize stressors -> excess glucagon, catecholamine, cortiosteriods
Pathogenesis of DKA?
increased insulin requirements due to tstressors. body goes to plan B (gluconeogen/lipolysis etc) to get sugar into cells despite plenty of sugar around in the serum
-excess fat breakdown
-beta oxidation overwhelms w/ acetyl coA
> beta hydroxybutyrate than acetoacetate
Symptoms of DKA (6)
Labs in DKA
hyperglycemia >300 mg/dL
metabolic acidosis w/ anion gap- give insulin till corrected
hyperkalemia (cells attempt to correct acidosis), polyuria -> net loss of K
Insulin is needed in DKA for 2 things
Lower glucose sugars
correct the metabolic acidosis prevent further ketone formation
Complications of DKA
murcomycosis - life threatening fungal infection
cardiac arrythmia (w/ low K)-> V tach and torsades (low Mg)
initial treatment of DKA (3)
IV K (repleat stores)
why is DKA less common in Type II DM
because a little bit of insulin is available to prevent lipolysis and associated ketone generation
Labs in hyperosmolar hyperglycemia state?
in type II DM
mental confustion, delerium severe dehydration, N/V, ab pain, high sugars but no fruity breath
hyperosmolar hyperglycemic state
Why are some type II DM capable of having ketosis
hereditary predisposition to toxic production that shuts down pancreatic secretion
Lactic acidosis is a rare but worrisome side effect w/ this DM drug
DMII Drug contraindicated w/ creatine >1.5
Most common SFx of DMII drug is hypoglycemia
DMII drug that is not safe in settings of hepatic dysfunction or CHF
DMII Drugs that should not be used in patients w/ cirrhosis or inflammatory bowel disease
DMII drugs not associated w/ weight gain (3)
DMII drugs metabolized by the liver; excellent for patients w/ kidney disease
DMII drugs good for weight loss
GLP 1 analogs
DMII medication that lowers LDL and triglercides as a bonus
GLP 1 analogs (2)
DPP4 inhibitors (3)
Metabolic syndrome 5 categories
Abdominal obesity - waist > 40 in males; >35 females
BP > 130/85
HDL < 40mg/dL male- 150 mg/dL
Fasting glucose >100
Meds linked to increase hunger (4)
Several DM drugs
- insulin/TZD/ sulfonuresas
Common causes of nonalcoholic steatohepatitis(4)
obesity, Type II DM, hyperlipidemia, insulin resisitance
the resistance -> lipid accumulation in the liver -> inflammation and PMN infiltration
progression fatty liver disease -> steatohepatitis -> cirrosis
Diagnose fatty liver disease (2)
- Magnetic resonance spectoscopy
Liver biopsy-> only those at risk for progression
Rx for fatty liver disease (5)
TZDs -pioglitazone, improves LFTs and possibly histology
Metformin shows improvement
Weight in kg / (height in meters)^2
Hormone released by adipocytes regulating hunger
Acts where (2)
in the hypothalamus
-inhibits Lateral nucleus
5 hypothalamus nuclei imlplicated in hunger
Dorsal medial nucleus -stimulates GI
Lateral area (hunger, leptin inhibits)
ventromedial area (satiety, leptin stimulates)
Lipodystrophy is what and could be due to ?
aplasia and distortion of the architecture of adipocytes
- ex: buffalo hump
Can be due to
- HIV medications (protease inhibitors)
- leptin deficiency
Causes of hypercalcemia (7)
-solitary parathyroid adenoma (MEN1?)
-parathyroid hyperplasia (MED2a?)
-PTHrP (squamous cell, renal cell, breast METs to bone)
Excess Vitamon D ingestion
milk alkali syndrome - antacid ingestion
granulomatous disease (sarcoid/TB- macrophage Vit D)
Increased bone turn over
Sympathetic cervical ganglia controls the parathyroids how?
controlling the bloodflow to the region
what cell secretes Calcitonin?
calcitonin - c cells/parafollicular in the thyroid
PTH - chief cells in the parathyroid
3 ways PTH raises Ca
increases reabsorption in the bone (w/phosphate)
increases reabsorption in the kidney (distal convoluted tubule)
increase 1 alpha hydroxylase activity -> Vit D3 (calcitriol)
Regulation of PTH
Ca sensors on chief cells respond to low serum levels
low Mg levels also stimulate PTH release but prolonged low Mg leads to less PTH
Low Mg can affect what hormone?
diarrhea, aminoglycoside, diuretics, alcohol abuse
How does PTH increase Ca reabsorption from the bone
binds to osteoblasts which up regulate RANK L which then binds to osteoclasts stimulating Ca release
PTH role on phosphate?
Phosphate trashing hormone
Vitamin D's roll on Ca and phosphate (3)
Vitamin D increases Ca and Phosphate reabsorption from the gut
Vitamin D increases bone reabsorption of Ca and Phosphate
low Ca and Phosphate stimulate active Vit D
Ca and Phosphate differences w/ Vit D and PTH
-increases Ca and phosphate reabsorption in the gut
PTH increases only Ca reabsorption in the gut
Most common cause of hypercalcemia ?
primary parathyroid adenoma
-osteitis fribrosa cystica/osteoperosis/osteomalacia/osteoarthritis
-ab pain/constipation/peptic ulcers/pancreatitis
Malignancies associated w/ PTHrP
Squamous cell - lung
renal cell carcinoma
Breast cancer to METs
Why do you get peptic ulcers w/ hypercalcemia
stimulates gastrin production
four conditions associated w/ hypercalcemia
-osteitis fribrosa cystica/osteoperosis/osteomalacia/osteoarthritis
-ab pain/constipation/peptic ulcers/pancreatitis
primary hyperparathyroidsm and secondary hyperparathyroidism have an increased lab value
primary hyperparathyroidism lab value
High Alk phos
secondary hyperparathyroidism lab value
Low Ca (drives PTH release)
alk phos is high
PTH is high
Phos is high (due to inability to excrete despite high PTH)
common cause is chronic renal failure, due to decrease gut Ca reabsorption and increased phosphate
most common cause of secondary hyperparathyroidism
chronic renal failure
refractory hyperparathyroidism is due to
lab values of Ca?
due to chronic renal failure, very high PTH despite having high Ca
Hypocalcemia is due to (4)
-accidental removal of parathyroids
-Pseudohypoparathyroidism - kidneys unresponsive to PTH
Poor Ca intake
Vit D deficiency
Acute pancreatitis (Ca precipitates out FA -> soaps and excreted)
Causes of hypo parathyroidism -> hypocacemia
Pseudohypoparathyroidism due to?
Lab values of Ca and PTH
Albrights hereditary ostreodystophy
AD kidney unresponsive to PTH
-> High PTH
-> Low Ca due to loss in the kidney
shortened 4th and 5th digits
osteritis fibrosis cystica
what starts the intrinsic pathway?
release of tissue factor from a cell binding to factor VII
Thrombin does what in the coag pathway
what creates it?
prothrombin(factor II) -> thrombin via Xa
- Factor V serves as an excellent
thrombin converts fibrinogen to fibrin to create a mesh and stabilize clots
what blocks Thrombin?
Which drug stimulates this effect?
Antithrombin (antithrombin III)
Factor 12 encourages what 2 paths
1. starts the intrinsic pathway and begins its shut down
2. encourages conversion of prekallikrien -> kallikrein
1. converts plasminogen -Plasmin
2.converts HMWK -> bradykinin
(vasodialation, permeability, pain)
where does bradykinin come from and what are its effects(3)?
Breakdown due to?
Kallikrien encourages conversion of HWMK -> bradykinin
Broken down by ACE enzyme
Hemophilia A is deficient in ?
Hemophilia B is deficient in ?
Alters PTT and PT how
A - 8
B - 9
longer PTT time w/ intrinsic factor modulation
no change in PT
Coagulation factors that serve as accelerants?
Factor 8a helps factor 9a activate factor 10 in the intrinsic pathway
Factor Va helps convert X -> Xa
Protein C and S deactivate the accelerants
Kallikrien's 2 functions
1. increases conversion of HMWK -> bradykinin
2. increases conversion of plasminogen ->plasmin
What additional components are needed in the coagulation cascade to assist (2)
PT measures what?
What is normal
measures the amount of time to clot after addition of tissue factor ( the extrinsic pathway -> uniquely VII) in addition to common path
1 is a normal INR
PTT measures what?
What is normal
PTT measures the amount of time to clot after adding something like silica, measures the intrinsic pathway (uniquely 12, 11, 9, 8) in addition to common path
normal is 35-40 seconds
Vitamin K deficiency has an effect on what coag factors?
What happens to PTT and PT?
Factors C, S
10, 9, 7, 2 are deficient
BOTH PTT and PT are elevated
macrohemmorrage such as hemarthrosis and easy bruising are due to defects in what?
coagulation cascade like hemophilia A or B
Factor V leiden deficency presents as?
most common form of hypercoagability
Factor 5 is mutated so protein C cannot shut down the cascade-> hypercoagable
Prothrombin G20210A is
mutation in the 3' untranslated region of adenosine to guanine in prothrombin gene leading to increase production of prothrombin and hypercoagability
2 less common states of hypercoagability after factor V leiden and Prothrombin mutation?
Protein C/S deficiency -> less to inactivate factor V
Antithrombin deficiency -> less to inactivate Thrombin
What hypercoagable state may not be helped w/ thrombin?
Preferred anticoagulant during pregnancy?
Heparin or LMWH
Use of Heparin?
Immediate anticoag desired
Platelets are decreasing after a new medication post an MI what is the drug?
MOA of toxicity
Heparin induced thrombocytopenia, -> IgG antobodies bind to Heparin bound to Platelet factor 4
-> activation and clumping (hypercoagable)
-> eventual removal -> thrombocytopenia
Low molecular weight heparins (2)
act more on factor Xa than antithrombin inducing
have better bioavailability
Toxicity w heparin (3)
thrombocytopenia (Heparin induced thrombocytopenia)
direct Xa blockers (2)
hirudin derived anticoags (3)
works by inhibiting thrombin ~ to natural antithrombin but dif MOA
skin tissue necrosis after a DVT be suspicious of what recently added drug?
Give K either oral/IV
Fresh frozen plasma for immediate help
Follow what labs w/ warfarin?
follow INR/PT w/ warfarin
follow PTT w/ Heparin
Clinical use of thrombolytic
see what lab values w/ PTT and PT?
converts plasminogen -> plasmin
-> increase PTT and PT
used in early MI (if no cath lab), early stroke, thrmbolysis of PE