This is the functional unit of the thyroid.

This is the functional unit of the thyroid.

This is filled with colloid, which is the major constituent of the thyroid mass. Colloid is composed of a mixture of _______ and ________.

This is the functional unit of the thyroid = follicle

This is filled with colloid, which is the major constituent of the thyroid mass. Colloid is composed of a mixture of thyroid hormones and thyroglobulin.

What cells produce calcitonin?

(Do you remember what calcitonin does?)

parafollicular cells

(calcitonin reduces blood Ca²⁺, opposing the effects of PTH by putting calcium into bones).

TPO:

-full name

-what role does it play in the production of thyroid hormones?

Thyroid Peroxidase -

a) this enzyme oxidizes iodide to iodine.

b) Iodine is added onto tyrosine to produce T3 and T4, which are stored in thyroglobulin (Tg).

**T4 aka thyroxine**

Thyroid Hormones, T3 and T4:

1) when is T4 in active form?

2) how is T3 produced?

3) which is synthesized in larger amounts?

4) which is stronger?

1) when is T4 in active form? unbound from TBG (1%)

2) how is T3 produced? T4 looses 1 iodine radical (de-iodination)

3) which is synthesized in larger amounts? T4

4) which is stronger? T3

a) TRH (hypothalamus)

b) TSH (ant pituitary)

c) T3, T4 (thyroid follicle)

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Control of thyroid function:

1) TSH inhibiting hormones (decr T3,T4 release)

2) TSH stimulating hormones (incr T3,T4 release)

3) auto-regulation of thyroid gland

1) TSH inhibiting hormones (decr T3,T4 release)

GH & cortisol

2) TSH stimulating hormones (incr T3,T4 release)

sex hormones (estrogen & androgen)

3) auto-regulation of thyroid gland

iodide levels: rate limiting factor in T3,T4 production

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-Increase BMR (incr body temp)

-role in bone growth/maturation

-increase ventilation (lungs)

-increase cardiac output

-increase renal function

-mostly catabolic (but anabolic in young pts)

growth retardation and mental retardation

**FYI: pituitary dwarfs DO NOT have mental retardation.

Metabolic action of TH in physiologic and large doses:

1) carbs (bld glucose)

2) protein

3) fat

1) carbs

Physiologic doses: T4 decreases glycemia from increased utilization

Large doses: hyperglycemia

2) protein & fat

Physiologic anabolic effect

Large dose catabolic effect

Most common cause of goiter

(other causes?)

Prolonged stimulation of TSH...

caused by iodine deficiency -->

inability to synthesize T3, T4 -->

low T3, T4-->

incr TRH-->

incr TSH-->

swelling of thyroid gland.

other: Goitrogens (turnip, cabbage, cassava) are substances that suppress the function of the thyroid gland by interfering with iodine uptake, which can, as a result, cause an enlargement of the thyroid

Meds which destroy iodine (lithium, sulfonylurea)

Low T4, high TSH -

most common cause?

severe form?

Primary hypothyroidism:

• Hashimoto thyroiditis - Most common cause (w/ or w/o goiter)
• Myxedema coma - severe form

Pt complains of sluggishness, deep voice, weight gain despite decr appetite & dieting, easily cold, constipation, weakness.

hashimoto's thyroiditis

(primary hypothyroidism,

low T4, high TSH)

antibodies vs TSH-receptors on the follicular cells of the thyroid gland (the cells that produce thyroid hormone), causing chronic stimulation of thyroid gland.

Graves' Disease

(primary hyperthyroidism,

high T4, low TSH)

high T4, low TSH -

1) most common cause

2) in elderly

3) seen in dieters

4) acute cause

thyroid hyperfunction:

1) graves disease (70-80%)

2) toxic multinodular goiter in elderly

3) exogenous administration of TH by dieters

4) gland destruction caused by infection

BP in

1) hypothyroidism

2) hyperthyroidism

BP in

1) hypothyroidism = high diastolic

2) hyperthyroidism = high systolic

Hyperthyroid manifestations:

1) Cardiovascular

2) Eyes

3) Muscles

4) Edema (where?)

1) CV = high CO heart failure

2) Eyes = exopthalamus from inflammatory response

3) Muscles = thyrotoxic myopathy (proximal muscle weakness)

4) Edema = pretibial myxedema

This is...

-increased by high estrogen, pregnancy, & oral contraceptives.

-decreased by glucocorticoids, nephrotic syndrome, & cirrhosis.

TBG: thyroxine-binding-globulin binds 99% of T4.

-Test free TH (TBG disorders)

-Test total TH (thyroid disorders)

-Test TSH level (ant pituitary disorders, secondary causes of thyroid dysfunction)

Thyroid Nodules:

1) benign (2)

2) malignant risk factors (2)

3) presentations (3)

1) benign = ademona, cyst

2) malignant risk factors = male, neck radiation

3) possible presentations (3) = single/multiple nodules, goiter, thyroid dysfunction

Thyroid Cancer - list 3 types.

1) most common

2) worst prognosis

3) best prognosis

a) Papillary (most common, best prognosis)

b) Anaplastic (worst prognosis)

c) Medullary (20% men, 80% sporadic).

CC: diarrhea and flushing.

Blood tests come back with high calcitonin levels.

Whats your dx and justification for sx/lab findings above?

Medullary Carcinoma (20% Men, 80% sporadic):

-serotonin secretion=flushing, diarrhea

-hyperplasia of C-cells=high calcitonin

• Acini cells secrete digestive enzymes (exocrine)
• Islets of Langerhans = endocrine (hormones to blood)
  
  • alpha cells secrete glucogon
  • beta cells secrete insulin
  • delta cells secrete somatostatin

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Insulin, produced by beta cells of endocrine pancreas, most useful just after eating.

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Glucagon, produced by alpha cells of endocrine pancreas, useful in fasting state when you are hypoglycemic.

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Summary from wiki: (I feel like this will be a test question):

• hypoglycemic state (Blood glucose <50mg/dl) OR during fasting: alpha cells release glucagon
  • MAIN EFFECT: binds to glucagon receptors on hepatocytes, causing the liver glycogenolysis (glycogen to glucose). As glycogen stores become depleted, glucagon  encourages the liver to synthesize additional glucose by gluconeogenesis, and this glucose is released into the bloodstream
  • other: stimulate conversion of protein to AAs (in muscle), and AA to glucose (in liver).  Also can breakdown fat to glycerol and fatty acids
    

• hyperglycemic state (blood glucose level >180mg/dl OR after eating): beta cells release insulin
  • Glucose: cellular uptake (in muscle and adipose tissue); storage as glycogen (in liver and muscle).
  • Fats: promotes fatty acid synthesis and prevents lipolysis.
  • Protein: increase prot synthesis (via incr AA uptake) and prevents proteolysis.
    

Insulin:

Inactive to active form conversion

1. Made as inactive pro-insulin by pancreas b cells.
2. b-cell peptidases remove connecting peptide.
3. Results in active hormone and inactive c-peptide

Glucose is an essential substrate for the metabolism of most cells. Because glucose is a polar molecule, transport through biological membranes requires specific glucose transporter proteins, of which there are many types.

1. Where is the insulin-regulated glucose transporter found? (*this means it is required)
   
2. Where is insulin not required to transport glucose?

1. Where is the insulin-regulated glucose transporter found? (*this means it is required)

Skeletal muscle and adipose tissue

2. Where is insulin not required to transport glucose?

Nervous System (this is a safety system of the brain)

Insulin promotes the growth and development in children and adults.  State 3 effects of insulin on each of the following systems...

1) glucose metabolism

2) protein metabolism

3) fat metaboism

1) glucose metabolism

2) protein metabolism

3) fat metaboism

Decribe insulin control, release, and half life.

-Controlled by blood glucose levels

-Beta cells in the islets of Langerhans release insulin in 2 phases:

1) Within 3-5 min, rapid PREFORMED insulin release

2) Over 2-60 min, sustained, slow release of newly formed vesicles that are triggered independently of sugar.

-t^1/2 = 15 minutes

Short term insulin absence

DM type I= wt loss, ketoacidosis

DM type II = wt gain, hyperglycemia/hyperosmolar states

Effects of long term insulin abcense

-33% DM type I pts progress to ESRD

-Retinopathy is leading cause of blindness in 20-74 y/o

-Macrovascular: Atherosclerosis, CAD, PVD, CVA

1. GLUCAGON (from pancreas alpha cells)
2. Catecholamines (epi, NE)
3. GH (from ant pit)
4. Cortisol (glucocorticoid from adrenal cortex)

1) hypoglycemia

2) incr AA concentration

3) strenuous exercise

Changes in cerebral function, headache, decr mentation, behavoral changes, seizures, coma

This is a result of what?  What is the acute  physiologic response?

Hypoglycemia

Phys Response:

1) initial parasym stim = hunger

2) later sympathetic stim = anxiety, tachycardia, sweating, skn vessel contriction

Hypoglycemia may cause hyperglycemia (Somogyi effect), secondary to actions of counterregulatory hormones 

Polyuria, polydipsia, polyphagia, ketoacidosis (DM type I), hyperosmolar state (DM type II)

This is a result of what? 

State a specific acute physiological responses to DM type I and type II.

Hyperglycemia

DM I: ketoacidosis ( ↑BG, ↓bicarb., ↓pH, +ketones

DM II: hyperglycemic hyperosmolar state (HHS) w/o ketoacidosis.

Autoimmune detruction of beta cells probably caused by genetic predisposition and triggering event (such as virus).

Onset?

Associated with what alleles?

frequency (%)?

therapy?

Type I DM:

Onset in childhood/young adulthood.

Assoc w/ HLA alleles.

10% of DM cases in US/EU.

Tx: exogenous insulin therapy.

Decreased insulin production, tissue insulin resistance, and increased hepatic glucose production caused by genetic factors and obesity leads to hyperglycemia despite presence of insulin.

Onset?

Type II DM:

Onset > 40y/o (although seen in youth b/c obesity).

1) common duct gallstones with biliary reflux and enzymatic activation

2) alcohol abuse

characterized by escape of activated panc. enzymes into pancreas & surrounding tissues with fat necrosis and autodigestion of pancreatic tissue and fat deposits in abdom. cavity and hemorrhage from necrotic vessels.

What is your Dx?  Possible complications (2)?

Acute pancreatitis

Complications: ARDS, ATN (leading to acute renal failure).

Chronic Pancreatitis:

1) most common cause and 4 others...

2) 2 types (which is seen in alcoholics?)

1) alcohol abuse (70% of cases), CF, trauma, hereditary, idiopathic.

2) Types:

a) Chronic calcifying pancreatitis: (calcified protein plugs form in panc. ducts)—seen most often in alcoholics

b) Chronic obstructive pancreatitis—usually caused by obstruction (by tumors or stenosis of the pancreatic duct).

Chronic Pancreatitis

Disease will progress, compromising exocrine and endocrine pancreas, resulting in DM and malabsorption.

GERD

pH<4.0=mucosal damage.

1) Foods - fatty, chocolate, ethanol, peppermint, onions, caffeine

2) Meds - smoking, CCBs, nitrates, some sedatives

3) Incr Intrabdominal Pressure - obesity, pregnancy, tight clothes, exercise

A pre-malignant condition in which normal squamous epithelium of esophagus is replaced with columnar cells (that line the stomach), giving rise to adenocarcinoma of esophagus.

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Pt presents with dysphagia w/o h/o of heartburn or GERD.

Endoscopy reveals...

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Pt presents with HPI of gradual progressive dysphagia (at first dry foods, now fluids).  Pt has substernal chest discomfort, foul breath, wt loss, and regurgitation.

Dx and complication.

Achalasia

Complication: Sigmoid esophagus - dilated and risk of perforation.

gastric and duodenal (duodenal 5x more common)

5mm diameter

through muscularis mucosae

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PUD - gastric vs duodenal ulcers:

1) more frequent in what age group?

2) which can become malignant?

3) in which is food a palliative factor of pain?

4) stress is a causative factor

1) duodenal (younger pts), gastric (55-70 y/o)

2) gastric ulcers can become malignant

3) duodenal ulcer pain relieved with food

4) NEITHER are caused by stress!

A gastrinoma - gastrin secreting tumor.  This causes parietal cells to produce more HCl despite food intake.

Name of condition.

Most commonly found where? (but also...)

What fraction are malignant?

90% develop what condition?

Name of condition. Zollinger-Ellison Syndrome (ZE syndrome)

Most commonly found head of the pancreas (duodenal wall, lymph nodes).

What fraction are malignant? 2/3.

90% develop what condition? PUD (RARE causative factor).

Colonizes in mucous secreting epithelial cells and secrete urease and produce ammonia (buffers), mucin-degrading enzyme, and damaging toxins.

What bacteria?

gm stain and shape

causative of what condition?

H. pylori

gm- rod with multiple flagella

PUD

PUD:

1) perforation occurs in what direction

2) penetration occurs in what direction

PUD:

1) perforation occurs in what direction - anteriorly

2) penetration occurs in what direction - into pancreas

**pt presents with rigidity and PAIN!**

Stress ulcers:

affected population

locations

-hospitalized pts (5-10% of ICU pts)

-fundus & proximal duodenum

Mouth to anus.

Highest incidence - sm intestine alone (40%) - terminal ileum

bloody diarrhea

1) Osmotic Diarrhea - lactose intol, meds (antacids, maalox)

2) Secretory Diarrhea - inhibition of absorption, incr in active secretion.  Cholera toxin stimulates secretion of anions (esp Cl-)...Na+ & H2O are pumped into lumen to balance charge.

3) decreased transit time (eg hyperthyroidism, IBS, stimulants) - hyperperistalsis decreases absorption.

Where is fat absorbed (bound to what)?

What characterized steatorrhea (causes?)?

Fat normally absorbed in upper jejunum, bound to bile salts, broken down by pancreatic lipase.

Steatorrhea: >20g/day fat in stool, evidence of malabsortive disorder.

Causes of steatorrhea: chronic pancreatits, DM, liver/biliary tract disease, sprue (celiac's), lymphoma

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Steatorrhea:

Malabsorptive disorder:

tetany - Ca def

paresthesias - Mg def

bleeding dis - K def

anemia - B12 iron def

LIVER general questions:

What % of cardiac output does the liver hold?

Epigastric pain could be from what part of liver?

Blood supply to/from liver.

Sinusoids carry what type of blood?

What % of cardiac output does the liver hold? 8%

Epigastric pain could be from what part of liver? L lobe problem

Blood supply to/from liver. hepatic artery supplies O2 blood. Portal vein drains intestines and goes to liver.  Hepatic vein drains liver to IVC.

Sinusoids carry what type of blood? venous & arterial blood to Central Vein.

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Biliary Tree (picture drainage and tube names in your head).

Bile

1) MAIN components

2) production

3) storage

4) release

1) MAIN components: bilirubin, chol, bile salts...

2) production: produced by hepatocytes in the liver, draining through the many bile ducts that penetrate the liver

3) storage: If the sphincter of Oddi is closed, bile flows to gallbladder, where it is stored and concentrated to up to 5x its original potency between meals.

4) release: Chyme in duodenum, the duodenum releases cholecystokinin (CCK), causing gallbladder to release concentrated bile to complete digestion.

Enterohepatic circulation of bile salts:

-what % reused?

-where are they reabsorbed and where do they go?

95% of the salts secreted in bile are reabsorbed in the terminal ileum and re-used. Blood from the ileum flows directly to the hepatic portal vein and returns to the liver where the hepatocytes reabsorb the salts and return them to the bile ducts to be re-used, sometimes two to three times with each meal.

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Liver functions in metabolism of:

1) Carbs

2) Proteins

3) Fats

1) Carbs

-Monosacc (glucose) gets to liver vis portal system, excess stored as glycogen.

-Gluconeogenesis: synth of glucose from AA, lactate, or glycerol

-Glycogenolysis: breakdown of glycogen into glucose

-Glycogenesis: formation of glycogen from glucose

2) Proteins

-deaminate AA to form ammonia

-produce urea for excretion

-synth plasma proteins

3) Fats

-chol synthesis

-lipogeneisis - production of TGs/ phospholipids

-fat aborption via Micelle cells

Liver Serum Enzymes:

1) rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose.

2) raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle and is therefore not specific to the liver.

3) levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. It is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients with Paget's disease.

4) an enzyme found in many body tissues, including the liver. Elevated levels may indicate liver damage.

5) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. It is raised in chronic alcohol toxicity. chronic.

1)ALT - rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose.

2) AST -  raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle and is therefore not specific to the liver.

3) ALP -  levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients with Paget's disease.

4) LDH - an enzyme found in many body tissues, including the liver. Elevated levels may indicate liver damage.

5) GGT- may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. It is raised in chronic alcohol toxicity.

Micelle

-where are they formed?

-essential for the absorption of...

Formed in the liver by bile salts.

required for small intestine absorption of fat soluble vitamines A,D,E,K.

The liver stores which vitamins/minerals?

Which is needed for synthesis of clotting factors II, VII, IX, X?

-Fat soluble vitamins (ADEK)

-Vit K needed for synthesis of clotting factors II, VII, IX, X

-B12

-Iron

-Copper

If liver function is impaired/biliary drainage blocked, _______bilirubin leaks out of hepatocytes and appears in the urine, turning it dark amber.

In hemolytic anemia, an increase in RBC breakdown results in an increase in ______bilirubin in the blood (since it is NOT water soluble, this bilirubin will not appear in urine.

If liver function is impaired/biliary drainage blocked, conjugated bilirubin leaks out of hepatocytes and appears in the urine, turning it dark amber.

In hemolytic anemia, an increase in RBC breakdown results in an increase in unconjugated bilirubin in the blood (since it is NOT water soluble, this bilirubin will not appear in urine.

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pre-hepatic jaundice (hemolytic jaundice) - increase in unconjugated bilirubin.

FYI Thalassaemia - Reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, thus causing anemia

Laboratory findings include:

• Urine: no bilirubin present, urobilirubin > 2 units (except in infants where gut flora has not developed).
• Serum: increased unconjugated bilirubin.

Liver tumor/CA, hepatitis, cirrhosis result in...

The presence of pale stools (acholic),  dark urine, &  pruritus suggest...

increased levels of conjugated (water soluble) bilirubin as a result of POST-HEPATIC (OBSTRUCTIVE) JAUNDICE.  Bile flow usually blocked at CBD.

Gilbert's Disease

Asymptomatic

Two types of gallstones and 3 Contributing factors to the formation of gallstones

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Cholesterol stones (usually green, sometimes yellow or white).

Pigmented stones (small, dark) - made of bilirubin and Ca salts.

CONTRIBUTING FACTORS:

1) bile composition abnormality

2) cholestasis

3) gall bladder inflammation

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Cholecystitis - usually stone in cystic duct.  Can be acute or chronic

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wiki -

Choledocholithiasis - stone in common bile duct. associated with 'colicky' pain, and because there is direct obstruction of biliary output, obstructive jaundice. LFTs: increased serum bilirubin, with high conjugated bilirubin. Liver enzymes will also be raised, predominately GGT and ALP, which are associated with biliary epithelium. The diagnosis is made using endoscopic retrograde cholangiopancreatography (ERCP), or the nuclear alternative (MRCP). One of the more serious complications of choledocholithiasis is acute pancreatitis

Cholangitis - An infection of entire biliary tract.

Cholangitis is a medical emergency and patients can rapidly succumb to acute liver failure or bacterial sepsis. The classical sign of cholangitis is Charcot's triad, which is right upper quadrant pain, fever and jaundice. Liver function tests will likely show increases across all enzymes (AST, ALT, ALP, GGT) with raised bilirubin. As with choledocholithiasis, diagnosis is confirmed using cholangiopancreatography.

autoimmune disease, destruction of intrahepatic bile ducts, incr mitochondrial autoantibodies, ANA.

Dx?

This is 1 intrahepatic cause of...

Primary Biliary Cirrhosis

This is 1 intrahepatic cause of cholestasis

Portal HTN causes:

1) pre hepatic (1)

2) hepatic (2)

3) post hepatic (2) **

Portal HTN contributes to what 3 clinical findings?

Portal HTN causes:

1) pre hepatic thrombosis of portal vein

2) hepatic cirrhosis, hepatitis

3) post hepatic RHF, pericarditis Clincal Sx= Budd CHiari Syndrome

Portal HTN contributes to what 3 clinical findings?

ascites, splenomegaly, varices

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State if the following causes of PORTAL HTN are pre, intra, or post hepatic

State if the following causes of PORTAL HTN are pre, intra, or post hepatic:

Ascites - increased fluid in peritoneal cavity

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-anemia

-thrombocytopenia

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1) esophagus

2) abdomen (caput medusa)

3) hemorrhoids

Liver Failure: disorders of synthesis and storage of the following lead to...

1) glucose (1)

2) protein (3): alb, clotting, infection

3) Decr chol (0)

4) Bile salts (2): fat, vitamines

1) glucose: hypoglycemia

2) protein:

-hypoalbuminemia = edema/ascites

-decr clotting factors = bleeding

-incr infection risk

3) Decr chol

4) Bile salts:

-impair fat absorption

-deficiency of fat soluble vit ADEK

When the liver fails...state the result: