3rd year 2012-2013 Abdomen

Physiology 2

Andries Gilde Dept Physiology, FHML a.gilde@maastrichtuniversity.nl

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Alcohol nourished this body

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Patient: A 38 year landscaper is brought to the E.R. by his foreman. Symptoms Shock Severe pain in upper abdomen and back Vomiting Shortness of breath Muscle weakness/pain Weight loss Putty feces
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Medical history
Alcohol abuse Cystic fibrosis

Labs

Urine: - glucose +, protein+, tea color Blood: - glucose , free fatty acids, protein = - amylase and lipase , CK+, myoglobine - Hb =, leucos =; normal diff. - CT: deviating structures of ductus pancreaticus, local calcifications
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D.D.
Acute pancreatitis, Type 2 Diabetes Mellitus, Rhabdomyolysis

Content
Patient Symptoms and possible causes

The pancreas
ENDO EXO

Importance of the pancreas in nutrient absorption

Carbohydrates Proteins Fatty acids Nucleic acids

Control of gastrointestinal secretions

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Boron & Boulpaep

Secretion 25%-50% cephalic 10%-20% gastric

Pancreas secretion

50%-80% intest.

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Secretion 25%-50% cephalic 10%-20% gastric

Pancreas secretion

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Secretion 50%-80% intest.

Pancreas secretion

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Muscarine receptor activation

Acetylcholinesterase inhibition by: Venom (snake, scorpion..) Insecticides (nerve gasses SARIN, VX)
Occupational hazards

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Production of pancreatic enzymes

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Production of pancreatic enzymes

Trypsinogen Chymotrypsinogen Proelastase Proprotease E Procarboxypeptidase B Amylase Lipase Colipase RNAse DNAse Trypsine inhibitor

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Boron & Boulpaep

Mechanisms to prevent autodigestion

1. enterokinase
Released by intestinal mucosa

2. Zymogen

3. Granules impermeable to the enzymes 4. Low pH 5. Non digestive proteases

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Acute Pancreatitis

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Gallstones/Cholelithiasis

Concise Pathology; Chandrasoma&Taylor

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Medical history
Alcohol abuse

Cystic fibrosis

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Role of CFTR in production of HCO3- rich pancreatic juice

Chloriderecycling
Interstitial space

CF

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Pathophysiology
Pancreatitis
Cause: Alcohol (m), gallstones (v), insecticides (occupational hazard) Mechanism: autodigestion of the pancreas/fibrosis

Cystic fibrosis
Slow release of enzymes due to defect chlorinechannel decreased HCO3--rich pancreatic juice production (fluidity) Autodigestion of the pancreas Respiratory problems
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Cystic fibrosis
CF is a monogenic disorder that presents as a multisystem disease. The first signs and symptoms typically occur in childhood, but about 5% of patients in the United States are diagnosed as adults. Due to improvements in therapy, >46% of patients are now adults ( 18 years old) and 16.4% are past the age of 30. The median survival is >37.4 years for patients with CF; thus, CF is no longer only a pediatric disease, and internists must be prepared to recognize and treat its many complications. CF is characterized by chronic bacterial infection of the airways that leads to bronchiectasis and bronchiolectasis, exocrine pancreatic insufficiency and intestinal dysfunction, abnormal sweat gland function, and urogenital dysfunction. (Harrison's Principles of Internal Medicine, 18e)

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Labs

Urine: - glucose +, protein+ Bloed:

-glucose , free fatty acids,

- amylase and lipase

protein =

- Hb =, leucos =; normal diff. - CT: deviating structures of ductus pancreaticus, local calcifications
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Endocrine Pancreas
Insuline and glucagon Skeletal muscle,liver and adipose tissue

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Pancreas polypeptide

Proinsuline C-peptide Amylin (Islet amyloid polypeptide)

Diabetes Care 31 (Suppl. 2):S284S289, 302008

Plasma glucose con. Activates Insulin release

( 5.6 mM)

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Insulin secretion in response to blood glucose concentration

2. 1.

Why??
Preformed insulin from granules + Insulin synthesis Preformed insulin from granules

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Insuline secretion Pancreas

inhibition
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Next to glucose insulin is released by:

Cholecystokinin (CCK) Acetylcholine Protein eta-adrenergic stimulation Glucagon

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Insulin's mode of action

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Skeletal muscle
Activity Epinephrine

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Glucose uptake of muscle depents on Insulin

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Table 16.4 . Family of glucose transporters

Name GLUT1 GLUT2 Tissue location All mammalian tissues Liver and pancreatic cells Km 1 mM 15 20 mM Comments Basal glucose uptake In the pancreas, plays a role in regulation of insulin In the liver, removes excess glucose from the blood GLUT3 GLUT4 GLUT5 All mammalian tissues Muscle and fat cells Small intestine 1 mM 5 mM Basal glucose uptake Amount in muscle plasma membrane increases with endurance training Primarily a fructose transporter

Copyright 2002, W. H. Freeman and Company

Stryer; Biochemistry
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Km Glut4=5mM

Km Glut2=15mM Glucokinase
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In time 20mM of glucose induces insulin secretion in GLUT2-/- islets

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Diabetes 49, 2000

Liver I Insulin
Glucokinase, insulin activated

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Liver II Glucagon

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Fate of Fat in de body

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Insulin promotes Glucose and Fat storing in adipose tissue

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Diabetes

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Insulin resistance

Nature Medicine 10, 1049 - 1050 (2004)

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Patient: A 38 year landscaper is broad to the E.R. by his foreman. Symptoms Shock Severe pain in upper abdomen and back Vomiting Shortness of breath

Muscle weakness
Weight loss Putty feces
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Labs

Urine:

-glucose +, protein+, tea color

Bloed: - glucose , free fatty acids, protein = - amylase and lipase , CK+ - Hb =, leucos =; normal diff. - CT: deviating structures of ductus pancreaticus, local calcifications
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Rhabdomyolysis
Rhabdomyolysis is the breakdown of muscle fibers resulting in the release of muscle fiber contents (myoglobin) into the bloodstream. Some of these are harmful to the kidney and frequently result in kidney damage.

http://www.nlm.nih.gov/medlineplus/ency

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Risk factors:
Alcoholism Certain inherited or genetic syndromes Crush Injuries Heat intolerance Heatstroke Ischemia or necrosis of the muscles (as may occur with arterial occlusion, deep venous thrombosis, or other conditions) Low phosphate levels Severe exertion such as marathon running or calisthenics Trauma Use or overdose of drugs, especially cocaine, amphetamines, statins, heroin, or PCP

http://www.nlm.nih.gov/medlineplus/ency

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Protein breakdown in muscle

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Aminoacid ketoacid interaction

Important pairs:
Aminoacid: Alanine Aspartate Glutamate -ketoacid: Pyruvic acid Oxaalacetate -ketoglutarate

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Prolonged starvation

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Protein absorption

PepT1

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Protein digestion

Enzymes from: Stomach Intestine Pancreas

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Patient: 38 year

Shock
Severe pain in upper abdomen and back Vomiting Shortness of breath Muscle weakness

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Diabetic complications resulting in cardiogenic shock and coma

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Silverthorn, Human Physiology

Or.
The result of renal failure due to Rhabdomyolysis

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Patient: 38 year Shock

Severe pain in upper abdomen and

back Vomiting Shortness of breath Muscle weakness

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Abdominal, visceral Pain referred to.

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Ganongs, Review of Medical Physiology, 23rd edition, McGraw Lange

Dermatomes
Areas of cutaneous sensory innervation from a spinal segment

Boron & Boulpaep, Medical Physiology

Literature
Guyton; Textbook of Medical Physiology Boron & Boulpaep; Medical Physiology Kumar; Pathological Basis of Disease Stryer; Biochemistry Alberts; Molecular Biology of the Cell. http://accessmedicine.com/features.aspx

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