Chapter 3: Disorders of the pancreas

Learning objectives:
• Understand the role of pancreas
as both an endocrine and an
exocrine organ
了了解胰腺作为内分泌泌器官和外分泌泌器官的作⽤用

• Describe the causes, symptoms,

and treatment methods of Type 1
and Type 2 diabetes
描述1型和2型糖尿尿病的病因、症状和治疗⽅方法

• Understand the acute and chronic

complications of diabetes
了了解糖尿尿病的急性和慢性并发症

http://technorati.com/lifestyle/article/is-diabetes-a-health- 1
verdict-for/ http://healthtipsinsurance.com/stories/21298/Cystic-Neoplasm-Of-Pancreas-RAPID-REVIEW.html
 Pancreas

• A glandular endocrine organ situated

between stomach and duodenum
器官
分泌泌
体内
的腺
之间
指肠
⼗十⼆二
胃和
位于

• Performs both endocrine (hormonal)

and exocrine (enzymatic) functions
执⾏行行内分泌泌(激素)和外分泌泌(酶)功能

• Endocrine: Islets of Langerhans secrete

hormones into blood vessels
内分泌泌:胰岛分泌泌激素进入⾎血管

• Exocrine: Acinar cells secrete enzymes

and ductal cells secrete bicarbonate
ions into pancreatic duct
外分泌泌:腺泡细胞分泌泌酶，导管细胞分泌泌碳酸氢盐离⼦子进入胰管

2
http://www.gopetsamerica.com/anatomy/pancreas.aspx
 胰岛和荷尔蒙

Pancreatic islets and hormones

• The endocrine pancreas resides in the islets of
Langerhans scattered throughout the more numerous
exocrine cells (acinar and ductal cells)
内分泌泌胰腺位于胰岛内，分布于众多的外分泌泌细胞(腺泡和导管细胞)中

• 3 major pancreatic hormones:

1. Insulin
- Secreted by β cells
- ↓ blood glucose levels

2. Glucagon
素
⾎血糖
胰⾼高

- Secreted by α cells
- ↑ blood glucose levels

3. Somatostatin ⽣生⻓长激素抑制素
- Secreted by δ cells
- Inhibits release of other pancreatic hormones http://droualb.faculty.mjc.edu/Course%20Materials/Physiology
3
%20101/Chapter%20Notes/Fall%202011/chapter_6%20Fall%20
抑制其他胰腺激素的释放 2011.htm
 Pancreatic enzymes
• 4 major types of pancreatic enzymes:
1. Amylase 淀粉酶
- Catalyzes the breakdown of starch 催化淀粉的分解

2. Proteases (e.g. trypsin)

酶)
⽩白
胰蛋
(如
酶
蛋⽩白
- Break down proteins into peptides
把蛋⽩白质分解成肽
- Secreted as an inactive form (e.g.
trypsinogen) 以非活性形式分泌泌(如胰蛋⽩白酶原)

3. Lipase 脂肪酶
- Digests lipids and fats into fatty acids
and glycerol 将脂类和脂肪分解成脂肪酸和⽢甘油

4. Nucleases 核酸酶
- Digest DNA and RNA
消化DNA + RNA 4
Saladin, (2010) Human Anatomy, 3rd Ed (McGrawHill Pub)
Pancreatic disorders

5
 Pancreatic disorders: Diabetes mellitus
胰腺疾病:糖尿尿病

• A heterogeneous disorder defined by the

presence of hyperglycemia glucometer

以⾼高⾎血糖为特征的异质性疾病。

• Causes:
1. Type 1
- Deficit of insulin secretion from β cells of
pancreatic islets 胰島素的虧損從 细胞的胰島素
β

2. Type 2
insulin resistance
- Lack of response by cells to insulin 细胞对胰岛素缺乏反应

3. Gestational 妊娠期
- Induced by pregnancy 由怀孕引致

6
http://www.hatfindo.com/wp-content/uploads/2010/03/Diabetes-mellitus.jpg
 Type 1 diabetes mellitus (insulin-dependent)
1型糖尿尿病(胰岛素依赖型)

• Due to destruction of pancreatic β cells in

an autoimmune reaction
Insulin deficit
由于⾃自体免疫反应破坏胰腺β细胞︎︎——胰岛素虧損

• Much less common (≈ 10% of all diabetes)

than Type 2 diabetes 比2型糖尿尿病少很多(约占所有糖尿尿病的10%)

• Occurs more frequently in children and

adolescents (≈ 1 in 500) juvenile diabetes
青少年年糖尿尿病

• A major factor for strokes, heart attacks,

lower leg amputation, kidney failure, and
blindness diabetic foot
中⻛风、⼼心脏病、下肢截肢、肾衰竭和失明的主要因素

• Treatment: Insulin injection

7
http://www.diabetesresearch.org/what-is-type-one-diabetes
 2型糖尿尿病(非胰岛素依赖型)

Type 2 diabetes mellitus (noninsulin-dependent)

• Type 2 diabetes may involve:

⾝身体细胞对胰岛素的抵抗
1. ↑ resistance by body cells to
insulin hyporesponsiveness低反應性: can’t sense
insulin——low insulin insensitivity
2. ↓ β cell producƟon fat/proteins --> glucose
3. ↑ glucose producƟon by liver
因為⾝身體時常感到沒有glucose， 所以liver 會製造很多。
liver 可以通過 breakdown of glycogen (glycogenolysis) 去減少glucose。 (gluconeogenesis )

• Often develops gradually in older

adults (≈ 50% cases found in people >
55 years old), most are overweight
通常在老年年⼈人中逐渐发展(在55岁的⼈人群中发现≈50%的病例例)，⼤大多数是超重的

• Excess fat makes it harder for cells to

respond to insulin
↑ insulin
resistance in people with obesity
过多的脂肪使细胞更更难应对胰岛素————︎︎↑在肥胖患者胰岛素抵抗

insulin receptor 不能感覺到insulin

8
http://we-care-you.blogspot.hk/2013/08/type2-diabetes.html
 Gestational diabetes

病
糖尿尿
妊娠
• A form of glucose intolerance which
occurs during pregnancy and
disappears after delivery ⼀一种葡萄糖耐受不良，发⽣生
于怀孕期间，分娩后消失

• Affects ≈ 10% of all pregnancies

胎盘激素(如雌激素)⼲干扰胰岛素功能------︎︎↑⾎血糖
• Placental hormones (e.g. estrogen)
interfere insulin function
↑ blood
glucose
estrogen and progesterone ——hormone 功能是maintain the thickness of the uterine lining (endometrium)

• Newborns are usually overweight

9
http://www.medindia.net/slideshow/pregnancy-diabetes-mellitus.asp#4
 Pathophysiological symptoms of diabetes (1)
糖尿尿病的病理理⽣生理理症状(1)

• Blood glucose levels rise (hyperglycemia) ⾼高⾎血糖

• Excess glucose appears in the urine (glucosuria) 糖尿尿病

• Glucose in urine exerts osmotic pressure in the

glomerular filtrate
Large volume of urine to
be excreted (polyuria) 尿尿液中葡萄糖产⽣生渗透压的肾⼩小球滤
液︎︎⼤大量量排出的尿尿液(多尿尿）

• Loss of water and high blood glucose levels

draw water from the cells
Dehydration

Thirst (polydipsia) 损失的⽔水和⾼高⾎血糖⽔水平提取⽔水
从细胞----︎︎脱⽔水︎︎-----⼝口渴(烦渴)

• Decreased use of glucose in many cells of the

body (starvation) ⾝身体许多细胞对葡萄糖的利利⽤用减少(饥饿)

• Lack of nutrients entering the cells stimulates

appetite (polyphagia) 多食症
10
http://www.foods-healing-power.com/type-2-diabetes-symptoms.html
 Pathophysiological symptoms of diabetes (2)
• Lack of glucose in cells 缺乏葡萄糖细胞

Breakdown of fats 分解脂肪

Ketone bodies (acetone or ketoacids) in
the blood ⾎血液中酮体(丙酮或ketoacids)

• Ketone bodies are important fuel for the

brain and heart during starvation or in
diabetic patients 在饥饿或糖尿尿病患者中，酮体是⼤大脑和⼼心脏的重要燃料

⾎血液中多余的酮体
• Excess ketone bodies in the blood
Bind减少体液的酸碱度
serum bicarbonate
Decrease pH of body
fluids
Ketoacidosis normal PH: 7.35-7.45
diabetes mellitus PH：？
酮症酸中毒

• Excess ketone bodies are excreted in urine

(ketonuria) or exhaled in breath (fruity
acetone breath) 多余的酮体通过尿尿液排出(酮尿尿)
或通过呼吸呼出(果香丙酮呼吸)
11
http://www.diabetestreatmentguide.org/prevent-diabetic-ketoacidosis-
acetone = volatile organic compounds (VOCs) using-5-simple-steps/
 Ketone bodies

• 2 out of 3 ketone bodies are carboxylic acids

12
http://eatingacademy.com/nutrition/ketosis-advantaged-or-misunderstood-state-part-i
 Fill in the blanks: Summary of diabetic symptoms
Decreased insulin secretion or increased insulin-resistant cells

glucose
Decreased __________ transport into cells

___________
starvation ______________
hyperglycemia Release of glucose Breakdown
(hunger) (high blood from the liver by of fats
glucose) glycogenolysis and
_________________
gluconeogenesis

ketone bodies
__________________
glucosuria ____________
(ketogenesis)
(excess glucose in
urine)

polydipsia
___________ Polyuria (large volume of urine) __________
ketoacidosis Ketonuria
(thirst)

Dehydration
13
Diagnosis and treatment for
diabetes

14
 Diagnostic tests for diabetes (1)
1. Fasting blood glucose level 空腹⾎血糖⽔水平
- Can be monitored at home by a portable
glucometer 可在家中由便便携式⾎血糖仪监测
- Diabetes: ≥ 7 mmol/L (more than once)

2. Glucose tolerance test 葡萄糖耐量量试验

- Fasting for 8 h and blood is taken 禁食8⼩小时，抽⾎血
- Intake of glucose drink (e.g. 75 g) and
then blood is collected after 2 hours
摄入葡萄糖饮料(如75
- Diabetes: ≥ 11 mmol/L (2 h) 克)，2⼩小时后采⾎血。

糖化⾎血红蛋⽩白(HbA1c)试验
3. Glycosylated hemoglobin (HbA1c) test
表⽰示过去三个⽉月
- Indicates an average of blood glucose 的平均⾎血糖⽔水平
levels over the past 3 months
because hemoglobin is
- Diabetes: > 7% circulate around 3months
Glycosylation 糖基化 15
http://www.hatfindo.com/wp-content/uploads/2010/03/Diabetes-mellitus.jpg
 Diagnostic tests for diabetes (2)
4. Glucose challenge test (for gestational 葡萄糖挑战试验(⽤用于妊娠糖尿尿病;代谢途径)
diabetes; 26-28 week)
- No fasting required 不需要禁食
- A glucose drink (e.g. 50 g) is given and then
blood is taken after 1 h 给予葡萄糖饮料(如50克)，1⼩小时后采⾎血
- Diabetes: ≥ 7.8 mmol/L (confirmed by glucose
tolerance test)

5. Urine tests for ketones (for patients with

ketoacidosis) 尿尿酮检查(酮症酸中毒患者)
- Dip test strip into urine and compare it with
the color chart 将试纸浸入尿尿液中，并与⾊色卡对比

http://www.drugs.com/cg/ketones-urine.html
16
http://www.medindia.net/slideshow/pregnancy-diabetes-mellitus.asp#4
 Treatments for diabetes (1)

• Four levels of control: reduce of absorption cholesterol

1. Diet 3 low 1 high eating principle
- ↓ food/calorie intake
- Complex carbohydrates with low
glycemic index ⾎血糖指数低的复合碳⽔水化合物
- Food with low cholesterol and lipid
levels 低胆固醇和低脂质的食物
- ↑ fiber intake
吃太多carbohydrate, 會轉化為monosaccharides (glucose)

2. Exercise
- ↑ uptake of glucose by muscles 肌⾁肉对葡萄糖的吸收

- ↓ weight and stress

- ↑ cardiovascular function
17
http://health.allrefer.com/pictures-images/diabetes-and-exercise.html https://ufhealth.org/diabetes-diet-type-1
 Treatments for diabetes (2)

3. Oral medications ⼝口服藥物

- Drugs that reduce insulin 减少胰岛素抵抗的药物(如⼆二甲双胍)
resistance (e.g. metformin)
- Drugs that stimulate insulin
release from β cells of pancreas
(e.g. sulphonylurea or Diabeta®)
药物刺刺激胰腺β细胞的胰岛素释放(如磺脲或Diabeta®)

4. Insulin replacement
- Recombinant insulin (Humulin)
synthesized by bacteria 细菌合成重组胰岛素(Humulin)
- Must be injected subcutaneously
(why?)
為什什麼胰島素是打針進去， ⽽而不是吃進去？ 因為protein hormone

http://www.healthline.com/hlcmsresource/images/imce/pregnancy-metformin-is-it-safe_thumb.jpg 18
http://www.odec.ca/projects/2007/wood7a2/timeline.htm http://www.drugs.com/pro/diabeta.html
Acute and chronic complications
for diabetes
糖尿尿病的急性和慢性并发症

19
 Acute complications for diabetes: Hypoglycemia
(insulin shock) 糖尿尿病急性并发症:低⾎血糖(胰岛素休克)

• Due to excess insulin injection

Low blood glucose
Decreased
CNS function
Weakness and
confusion
惑
软弱和困
系统功能︎︎
中枢神经
——︎︎降低
⾎血糖低
胰岛素---
• 了了过多的
Occurs following vigorous exercise,
low food intake etc.
发⽣生在剧烈运动、低食物摄入量量等

• Can cause brain damage or death

• Treated by concentrated
carbohydrate (e.g. fruit juice or
candy) or intravenous injection of
glucose or glucagon ⽤用浓缩碳⽔水化合物(如果汁或糖果)或静
脉注射葡萄糖或胰⾼高⾎血糖素处理理

20
http://www.buzzle.com/articles/how-to-treat-insulin-shock.html
 糖尿尿病的急性并发症:糖尿尿病酮症酸中毒
Acute complications for diabetes: Diabetic ketoacidosis

• Due to insufficient insulin; common in Type

1 patients 胰岛素不⾜足;在1型病⼈人中很常⻅见

• Progressive signs: Hyperglycemia
Polyuria

Dehydration
Ketoacidosis
Coma
进步的迹象:⾼高⾎血糖,︎︎多尿尿症,︎︎脱⽔水,︎︎酮症酸中毒︎︎和昏迷

• Effects of ketoacids in blood:

1. Acetone breath 丙酮⽓气 碳酸氢盐⾎血液结合,︎ ︎Decreased⾎血
清pH值、︎︎失去意识
2. Bind bicarbonate in blood
Decreased
serum pH
Loss of consciousness
腹痛、恶⼼心和呕吐
3. Abdominal pain, nausea and vomiting lipolysis
4. Rapid and deep breathing 快速呼吸

• Treated by administration of insulin and

bicarbonate bicarbonate can react with ketoacids
⽤用胰岛素和碳酸氢盐治疗 21
http://ncpnanda.blogspot.hk/2013/01/fluid-volume-deficit-related-to.html
 Chronic complications of diabetes: Microangiopathy
微⾎血管病

阻塞和⽑毛细⾎血管破裂或⼩小动脉
——︎︎坏死——︎︎损失功能
• Obstruction and rupture of
capillaries or small arteries

Necrosis
Loss of function
变
膜病
視⽹网

• Retinopathy
视⽹网膜⽑毛细⾎血管破裂
- Capillaries in retina rupture
出⾎血 貧⾎血

Blindness

• Nephropathy 腎病 ultrafiltration
变性肾脏的肾⼩小球——︎︎肾功能衰竭
- Degeneration of glomeruli in
kidney
Renal failure Bowman's
capsule

glomerulu
s

Bowman's capsule 22
http://www.cram.com/cards/path-spring-images-1751891 urine http://health.rush.edu/healthinformation/care%20guides/28/000289.aspx
 糖尿尿病的慢性并发症:⼤大⾎血管病变

Chronic complications of diabetes: Macroangiopathy

• Blockage and rupture of large

arteries ⼤大动脉阻塞和破裂
cholesterol plaque

Heart attacks and strokes

hyperglycemia ⾼高⾎血糖
endothelial cells
glycated proteins and lipids
glycation (glycosylation)

23
http://health.rush.edu/healthinformation/care%20guides/28/000289.aspx
 Chronic complications of diabetes: Neuropathy
糖尿尿病的慢性并发症:神经病

• Peripheral neuropathy can lead to

impaired sensation, numbness,周围神经病变可导致感觉受损、
⿇麻⽊木、刺刺痛和肌⾁肉萎缩
tingling, and muscle wasting

• Increased risks of tissue damage

and infection if vascular 如果⾎血管损伤和感觉损
impairment and sensory 伤同时存在，组织损伤
和感染的⻛风险增加
impairment coexist
⾃自主神經退化
• Autonomic nerve degeneration

Urinary incontinence 尿尿失禁

Impotence or infertility
陽痿/不孕

24
http://www.health.com/health/incontinence-woman/ http://tootallfritz.com/2012/05/22/neuropathy-awareness-run/
 Chronic complications of diabetes: Infections
糖尿尿病的慢性并发症:感染

• Macroangiopathy and increased

glucose levels favor infections
⼤大⾎血管病变和葡萄糖⽔水平升⾼高有利利于感染

• Diabetic foot: Infections in feet and

legs tend to persist because healing
is slow
Ulcer
Gangrene

Amputation
⽂文字

• Fugal infections (e.g. Candida

albicans): Persist in body folds, oral
cavity, and vagina
⽂文字

http://www.everydayhealth.com/diabetes-pictures/10-diabetic-skin- 25
problems.aspx#/slide-3 http://www.specialistvascularclinic.com.au/peripheral-vascular-disease.html
 Chronic complications of diabetes: Cataracts

⽩白內障
• Cataract = Clouding of the lens of the
eye 眼睛晶状体的混浊
hydroxyl groups

• Due to abnormal metabolism of

glucose
Accumulation of sorbitol
and water in the lens

Reduced transparency in the lens

Blindness

• Treatment: Cataract extraction

26
http://www.varga.org/Physician%20Assistant%20Photos.htm http://www.sightsurgeryinternational.com/cataracts_explained.html
 Clinical case study

• Mr. F. was diagnosed with Type 2 diabetes at age 46.

• Overweight, enjoyed foods with high carbohydrate and fat content.
• Family history: Mother and brother had diabetes.

1. What would you recommend him to do so as to lower his blood glucose

levels?
dietary control + : drugs that reduce insulin resistance (or stimulate insulin release)
例例如：metformin
2. List the factors which may contribute to diabetes in Mr. F.

3. At the age of 50, Mr. F. found that his vision was cloudy in one eye. What
could be the problem? Explain how such a complication arises and
suggest a possible treatment.
Cataracts

27
Modified from: Gould and Dyer. Pathophysiology for the Health Professions. 4th Ed., Saunders Elsevier