Internal Medicine (MERGED) (SEM2) - 2017 Batch

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01. General introduction (1)·················································································································································································································· 1

02. Hypopitutary (1)···························································································································································································································· 57
03. Adrenal disease (1)·····················································································································································································································104
04. CUSHING(英文) (1)···················································································································································································································· 148
05. Hyperthyroidism2 (1)·················································································································································································································· 203
06. 2014 diabetes 留学生讲义 (1)····································································································································································································· 279
07. Anemia -zk (1)···························································································································································································································· 280
08. AA-ZK (1)···································································································································································································································· 304
09. Iron Deficiency Anemia2014 (1)································································································································································································· 341
10. Hemolytic anemia (1)·················································································································································································································· 382
11. Hemophilia (1)···························································································································································································································· 403
12. Immune Thrombocytopenic purpura (1)····················································································································································································· 419
13. Leukemia (1)······························································································································································································································· 440
14. LymphomaEng (1)······················································································································································································································ 513
15. Multiple myeloma (1)·················································································································································································································· 569
17. Gastritis( HAN)2014····················································································································································································································588
18. Inflammatory Bowel Disease (1)································································································································································································· 631
19. XinjingHan2014-Gastrointestinal Bleeding (1)············································································································································································762
Bleeding disorders for teaching (1)··································································································································································································· 878
chronic diarrhea pancreatitis(NEPAL)······························································································································································································ 908
for exam imp (1)································································································································································································································983
INTERNAL MEDICINE IMPORTANT (1)·························································································································································································· 984
Peptic ulcer(xinjing han)··················································································································································································································· 994
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GENERAL
ENDOCRINOLOGY
The second hospital of

Chongqing medical university ,
Liu Dongfang
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The main subjects

 Definition of endocrinology
 Hormone classification
 Mechanism of hormone action
 Regulation of hormone
 Disorders of the endocrine system
 Laboratory test
 Treatment of endocrine diseases
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Definition of Endocrinology (A)
• Endocrine: The term endocrine refers to

the process of secretion of biologically
active substances into the body. This
contrasts with the term exocrine, which refers
to external secretion, generally via
anatomically identifiable ducts, such as into
the gastrointestinal tract. As the term is
ordinarily used, an endocrine gland or cell is
one that secrets substances, referred to as
hormones, that exert regulatory functions .
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Definition of Endocrinology (B)

 Hormone: The hormone is a substance that is
secreted by cells and travels through the
circulation, where it exerts biologic regulation
actions on other cells by binding to the specific
receptor.
 Receptor: The receptor is a molecule to which
the hormone binds to elicit its actions. A receptor
has two functions. First, it must be able to
distinguish the hormone. A receptor must be
capable of binding the hormone with great
affinity and also must not bind extraneous
substances. Second, the receptor must be able
to transmit the information gained from the
binding to trigger a cellular response. 4
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Types of hormone signalization

• Endocrine
• from gland via blood to a distance
• Neurocrine
• via axonal transport and then via blood
• Paracrine
• neighboring cells of different types
• Autocrine
• neighboring cells of the same type or the
secreting cell itself
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Hypothalamus:
•GHRH, CRH, TRH, GnRH
Hormone production:
•Somatostatin “Classic” glands
•ADH
Epiphysis:
Pituitary: •Melatonin
•Growth hormone
•Prolactin Thyroid gland:
•ACTH, MSH •T3, T4
•TSH •Calcitonin
•FSH & LH
Parathyroid
•Oxytocin glands:
•ADH •Parathyroid h.
Pancreas: Adrenal cortex:

•Insulin •Cortisol
•Glucagon •Aldosterone
•Androgens
Ovaries:
•Estrogens Adrenal medulla:
•Progesterone •Catecholamines
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Hormone production:
Endothelium:
Less traditional sources
•Endothelins
•NO
Cardiocytes:
•Prostanoids,...
•ANP
Immune system:
•Cytokines
Platelets, mesenchyme:
•Growth factors Kidney:
•Erythropoietin
•RAS
Placenta: GIT:
•All hormones •Gastrin
•Cholecystokinin
•Secretin,...
Adipocytes: Gonads:
•Leptin •Inhibins
•Adiponectin •Activins
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Hormone classification (A)

Hormones are classified into four major
groups depending on their biochemical
structure and methods of synthesis.
 1. Peptides and proteins
Form the great majority of all hormones.

Include all of the hormones of the
hypothalamus, pituitary gland, parathyroid
glands, gastrointestinal tract, and
pancreas.
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Polypeptide and protein

hormones
Most of the hormones in the body.
• Protein = more than100 aminoacids
• Peptides = less than 100 aminoacids
Water soluble – easy reaching the target tissue
by circulatory system
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Hormone classification (B)

Amino acid derivatives
• Amino acid derivatives (Amines )
Small water-soluble compounds derived
from amino acids
Hormone derived from tyrosine
Include the thyroid hormones(T3 and T4)
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Hormone classification (C)

Steroid hormones
• Synthesized from cholesterol
• Not stored, but possible quick utilization
from cholesterol in the blood
• Lipid soluble – diffuse across the cell
membrane → interstitial fluid → blood
• Include hormones of the adrenal cortex,
gonads (ovary and testes), and placenta
and active vitamin D
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Hormone classification (D)

Eicosanoids
• Derived from arachidonic acid
• Prostaglandins and leukotrienes
• Adrenal medullary hormones (the
catecholamines, and dopamine).
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Mechanism of hormone action

• The specificity of the hormone for the cells
of its target tissues depends on the fit of
the hormone to its receptor.
• There are two types of mechanisms of

hormone action according to the receptor.
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Hormone receptors
• Location:
– In or on the surface of the cell membrane – proteins,
peptides, catecholamines
– intracellular :In the cell cytoplasm – steroid
hormones or In the cell nucleus – Thyroid hormones
• Hormonal receptors are large proteins, each cell has 2
000 – 100 000 receptors
• Receptors are usually highly specific for single
hormone
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Mechanism of hormone action (A)

 Through the cell membrane receptors
Most peptide 、protein hormone and catecholamine

hormones act at the surface of the target cells by
binding to a specific receptor on the external
membrane of the cell (cell membrane
receptor),where they stimulate the activity of the
enzyme, adenyl cyclase ,and the production of
cyclic adenosine monophosphate (cAMP).
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Mechanism of hormone action (A)

The function of cAMP is to act as a“second
messenger” by accepting the information
offered by the hormone-receptor complex
and transmitting it to its molecular
destination within the cell. This is achieved
by the activation of protein kinase enzymes
in the cell.
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Figure1.The mechanism of action of peptides

and proteins hormone with cAMP as second
messenger
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Mechanism of hormone action (B)

 Through the cytoplasmic or nucleus
receptors.
steroid and thyroid hormone act for the
most part by binding to intracellular
receptors.
Steroid hormones are lipid soluble, in addition to
their small size ,accounts for their ability to diffuse
freely across the cell membrane. Receptors for
steroid hormone, located in the cytoplasm of target
tissue ,are not attached to cytoplasmic organelles
and for this reason they are sometimes referred to
as mobile receptors.
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Steroid hormones pass

through the cell membrane of
the target cell.
The steroid hormone binds

with a specific receptor in the
cytoplasm.
The receptor bound steroid

hormone travels into the
nucleus and binds to another
specific receptor on the
chromatin.
The steroid hormone-

receptor complex calls for
the production of messenger
RNA (mRNA) molecules,
which code for the
production of proteins.
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Regulation of hormone
 The relationship between the nervous and
endocrinology.
 Hormone release often has rhythmic patterns.
 Specific stimuli received by the endocrine
cells cause them to increase their hormone
secretion .Some stimuli decrease secretion
of hormone
 Feedback regulation
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Regulation of hormone(A)
 The relationship between the nervous
and endocrinology
The nervous system has evolved to release
regulatory substances(neurotransmitters ) from
nerve terminals that act across synaptic
junctions on adjacent cells. These substances
may travel considerable distances to act , but
when they do so, this generally occurs along the
axons.
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The brain is also an endocrine gland, it
is the major source of some hormones.
The hypothalamic releasing hormone or
factors include: thyrotropin releasing
hormone(TRH) , corticotropin releasing
hormone(CRH), growth hormone releasing
hormone(GHRH), gonadotropin releasing
hormone (GnRH), somatostatin ,and
dopamine .
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The Pituitary also can produce main five
type hormone, it include :
Adrenocorticotropic hormone (ACTH)
Thyroid stimulating hormone (TSH)
Growth hormone(GH)
Follicle-stimulating hormone(FSH )and
luteinizing hormone (LH)
Prolactin (PRL)
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Central Roles of the

Hypothalamus and Pituitary
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Regulation of hormone (B)

 Hormone release often has rhythmic
patterns.
1). Day-night(circadian)rhythms, e.g.
adrenocorticotropic hormone (ACTH),
prolactin, GH,TSH.
2). Monthly rhythms, e.g. oestrogen and
progesterone have a 28-day cycle, a
menstrual cycle.
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Regulation of hormone release

• Rhythms
– circadian
600
Cortisol 500
(nM)
400
300
200
100
0
09 21 09
Time of day
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Pulsatility in
GnRH & LH release
14 GnRH (pg/10 min)
LH (ng/ml)
12
10
0
12:00 14:00 16:00
Time of day
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Monthly rhythms –
Menstrual cycle
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Regulation of hormone (C)

 Specific stimuli received by the
endocrine cells cause them to increase
their hormone secretion .
1)Nervous stimuli induce adrenaline
release in the adrenal medulla.
2)Biochemical stimuli induce the secretion
of hormones. e.g. glucose induces insulin
release from the islet.
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Regulation of hormone (D)
 Some stimuli decrease hormone

secretion of hormone ,e.g. somatostatin
(GHIH) released by hypothalamus
decreases the amount of GH released by
anterior pituitary gland.
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Regulation of hormone (E)

 The concentration of the secreted
hormone in the blood, and /or the effects
produced by the hormone , control
subsequent secretion of the hormone ,this
is called feedback loop system, including
negative feedback (common) and
positive feedback.
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• Negative feedback is the most common
type of regulatory loop in biological system ,
Which means the level of hormones in
circulation or the response produced by the
hormone negates or reverses the original
stimulus ,decrease the secretion of their
stimulating hormone for example ,ACTH
stimulates the release of cortisol, cortisol in turn
inhibits the ACTH release.
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Combined feedback
Stress etc.
CRH secretion in hypothalamus
stimulation
ACTH secretion in pituitary
↑ plasma ACTH
inhibition
cortisol secretion in adrenals
↑ plasma cortisol
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• In some cases , hormonal control system in the
body can operate as positive feedback systems,
in these systems ,the response augments rather
than attenuates the stimulus. Pregnancy is an
example of a hormonal positive feedback system,
as the fetus grows, the feto-placental
unit ,produces increasing amounts of the steroid
hormones estrogen and progesterone, these
hormones operate in such a way as to maintain
the placenta and support pregnancy.
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• In conclusion ,A variety of mechanisms
regulate circulating hormone levels .a
hormone may be regulated by their
circadian rhythms、feedback inhibition by
hormones of their synthesis and or
release、stimulating or inhibiting by other
biochemical substances or brain
hormone . In some instances complex
regulatory networks are present.
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Disorders of the endocrine system

Hormones deficiency syndromes(A)
 Hypofunction of Endocrine Glands
Endocrine glands may be damaged by neoplasia,
infections, hemorrhage, autoimmune disorders,
and other causes.
A deficiency of a hormone that controls the synthesis
and release of another hormone may result in a
syndrome, which stimulates a primary deficiency of
that target organ. Thus, hypothalamic lesions resulting
in impaired secretion of releasing hormones may be
manifested by pituitary dysfunction, which in turn may
result in abnormal in the function of its various target
organs.
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Hormones deficiency syndromes(B)
 Hormone Deficiency Secondary to
Extraglandular Disorders.
Extraglandular disorders can result in
hormone deficiency.They may involve
defective conversion of prohormones to
active forms, enhanced degradation of
hormone,or the production of substances
(antibodies ,hormone antagonists) that
block the actions of hormone.
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Hormones deficiency syndromes(C)
 Hyporesponsiveness to hormones
Hormone levels may be normal or even
elevated in the presence of manifestations of
endocrine deficiency. These conditions may be
due to these problems, e.g. antibodies to the
insulin receptor and abnormal conversion of
testosterone to dihydrotestosterone ;They may
also result from decreased ability of the
endocrine target gland to respond to hormone.
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Hormones deficiency syndromes(D)
 Abnormal Production or Administration
of Antagonists
Rarely, endogenously produce or exogenously
administered substances may produce a
hormone-resistant state. Antibodies to the
insulin receptor may produce a hormone-
resistant state.
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Hormone Excess Syndromes (A)
 Hyperfunction of Endocrine Glands

The most common cause of hormone excess
syndromes is hyperfunction of endocrine glands
secondary to tumors or hyperplasia. Such as
hyperfunction of thyroid, adrenals , parathyroids
is caused by hyperplasia or tumors.
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Hormone Excess Syndromes (B)
 Ectopic Hormone Production

Hormone may be produced in excess by cells
of endocrine or nonendocrine origin that are not
normally the primary source of a hormone. For
example , small-cell lung carcinoma can
produce the ACTH ,induce the ectopic ACTH
syndrome.
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Hormone Excess Syndromes(C)
 Hormone Administration
Hormone excess states may occur when
hormone are used to treat non endocrine
disease, hormone replacement therapy is
excessive .for example , use cortisol for a long
time to treat the autoimmune disease that can
let the hypercortisolism happen.
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Hormone Excess Syndromes(D)
 Tissue Hypersensitivity
Endocrine excess syndromes caused by
hypersensitivity of target tissues are uncommon.
Thyroid hormones increase the catecholamine
receptors in certain tissues and this lead to
excessive bate-adrenergic stimulation.
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Hormone Excess Syndromes(E)
 Autoimmune Disease
The most frequent situation in which this occurs
in thyrotoxicosis.
 Hormone Biosynthetic or metabolic defects
Certain adrenal steroid biosynthetic defects (the
21a- and 11a- hydroxylase syndrome) result in
overproduction of hormone
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Hormone Excess Syndromes(F)
 Secondary Hormone Hypersecretion

Hypersecretion of hormone may be due to
excessive physiologic stimulation of glands that
are basically normal. For example, Secondary
hyperinsulinism occurs in obesity.
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Multiple Endocrine syndromes (A)
 Multiple endocrine deficiencies

The most common syndrome of multiple
endocrine deficiencies may involve
immunologic destruction of pancreatic
islets, thyroid, adrenals, and gonads .
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Multiple Endocrine syndromes (B)
 Multiple endocrine neoplasia (MEN)
At least three syndromes of multiple endocrine
hyperfunction result from hyperplasia, adenomas, or
carcinomas of endocrine tissues ,termed multiple
endocrine neoplasia (MEN) which includes three
types :type 1,2a,and 2b.
Type1 is associated with Hyperfunction of parathyroid,
pancreatic islets and pituitary.
Type2a is associated with pheochromocytoma,
medullary carcinoma of thyroid, parathyroid carcinoma.
Type2b is associated with medullary thyroid carcinoma,
pheochromocytoma, and other features such as
neuromas.
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Midgets
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Cretinism
cretinism, caused by severe iodine deficiency during pregnancy, is

the world's most common preventable cause of mental retardation
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Gigantism
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Acromegaly
Epiphyseal plate is closed

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Hypercortisolism
purple striae ; plethora ; acne
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Laboratory Testing
• Hormone level
The hormone level can provide the direct
evidence for endocrine disorders, but because
the hormones are regulated by various
factors ,hormone levels should be evaluated in
this context. The significance of hormone levels
can sometimes be evaluated only by the
simultaneous measurement of more than one
hormone.
The level of free rather than total hormone is
usually the best index of the effective hormone
concentration in plasma.
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Laboratory Testing
• Dynamic Testing
Stimulation test :Provocative testing assesses
the ability of a gland to respond to stimuli as an
index of its reserve capacity. This is especially
useful when plasma or urinary hormone
measurements are borderline.
Inhibition test:When endocrine hyperfunction ,
the inhibition tests can assess the extent to
which the normal physiologic mechanisms that
control hormone release are suppressed or the
degree of autonomy of the hormone –producing
tumor or hyperplastic gland.
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Treatment of endocrine diseases

 Hormone replacement is given in
endocrine deficiency syndrome.
 In hormone-excess syndromes, a variety
of approaches are used .For example,
hyperfunction tumors are removed , drugs
are given to block hormone production,
such as propylthiouracil (PTU) for
thyrotoxicosis.
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Learning main points

 Definition : Endocrine,
Hormone,
Receptor,
Negative feedback ,
The second messenger ,
Multiple endocrine neoplasia (MEN) ,
 Hormone classification and their action
mechanisms
 Hormone regulation.
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Pituitary Disease
The second hospital of

Chongqing medical university
Liu Dongfang
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Anatomy and function of the

Pituitary
• The pituitary gland include the anterior lobe,

the posterior lobe
• The anterior pituitary gland consists of
epithelial cells of varying sizes and
shapes ,each secretory cell of the anterior
pituitary is provided with sets of information
from the hypothalamic centers through its
neurons and neurosecrectory cells.
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The main anterior pituitary hormones

and its physiology cell、
cell、function
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The physiology and function of

posterior pituitary
• The posterior pituitary is composed of nerve tissue.
• There are two types of hormone, which are formed in
the hypothalamus and through out long axons and
are discharged in the posterior lobe.
• The main hormones of posterior lobe are oxytocin
and vasopressin (ADH).ADH is an antidiuretic
hormone, Oxytocin has considerable potency in
stimulating uterine and milk ejection.
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The main diseases about pituitary
• Hypopituitarism
• Diabetes insipidus
• Acromegaly and giantism
• Prolactinoma
6
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Hypopituitarism
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What’’s wrong with the man?

What
Let’s see a patient. Mr. Liu ,ten years ago he encountered a pituitary tumor section , gradually he felt weakness, fatigues,
weight loss, and dizziness, his skin became dry, pale, finely textured. what’s wrong with the man?
8
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The Concept of the Hypopituitarism
• Impairment of anterior pituitary or

hypothalamus leads to hyposecretion of
anterior pituitary hormone, present itself with
related target gland hypofunction .
• The primary Hypopituitarism is caused by
anterior pituitary hypofunction
The secondary Hypopituitarism is caused by disease
which affect hypothalamus
9
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The main hypothalamus 、pituitary 、

target gland axis
1)Hypothalamus －pituitary－adrenal gland

CRH ACTH Cortisol
2)Hypothalamus －pituitary－thyroid gland
TRH TSH T3、T4
3)Hypothalamus －pituitary－ sex gland
LRH LH E2、T(testosterone).
GNRH FSH
10
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Etiology
Mass lesions (the common cause ):
pituitary tumor
aneurysms, metastatic carcinoma,
granulomas,
pituitary abscess.
apoplexy
11
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Etiology
Other causes without mass lesions :
• Autoimmune hypophysitis,
• postpartum pituitary necrosis (Sheehan’s syndrome) ,
• Idiopathic disease,
• Trauma,
• Radiation,
• Surgery (common),
• Encephalitis,
• Hemochromatosis,
• Autoimmunity,
• Stroke.
12
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Clinical Findings
Symptoms and Signs :
Hypogonadism and infertility (occur early )
Hypothyroidism
Adrenocortical hypofunction (important )
Growth hormone(GH) deficiency
13
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Clinical Findings
Manifestations of hypopituitarism vary

depending upon which specific hormones
are lacking and whether their deficiency is
partial or complete.
14
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Symptoms and Signs

Gonadotropin deficiency (A)
• Gonadotropin deficiency includes loss of
luteinizing hormone (LH) and follicle-
stimulating hormone (FSH), which causes
hypogonadism and infertility.
• In acquired gonadotropin deficiency, both
men and women lose axillary, pubic, and
body hair gradually, particularly if they are
also hypoadrenal .
• Gonadotropin deficiency symptom appear
more early in the process of this disease.
15
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Symptoms and Signs

Gonadotropin deficiency in women (B)
• The two principal function of the ovaries are
production of ova and secretion of estradiol, so the
clinical presentation of hypogonadism in women are
infertility and the manifestations of decreased
estradiol secretion .
• When estradiol deficiency occurs after puberty has
been completed ,the features are amenorrhea,
reduction in breast size, a decrease in general
sense of well-being and ,if the deficiency is severe,
vasomotor instability (hot flashes) and vaginal
dryness happen.
• If estradiol deficiency occurs prior to the
anticipated onset of puberty, the result is
incompleted puberty.
16
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Symptoms and Signs

Gonadotropin deficiency in men (C)
• The two functions of the testes are sperm production
and testosterone secretion, so the clinical
presentations of male hypogonadism are those of
decreased sperm production and those of decreased
testosterone secretion ,which depend on when the
deficiency occurs.
• When testosterone deficiency occurs after puberty
has been completed, energy and libido decrease
within weeks, and men may note diminished beard
growth.
• when it occurs prior to the anticipated onset of
puberty, the result is incomplete puberty
17
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Symptoms and Signs

TSH Deficiency
• Thyroid-stimulating hormone (TSH)

deficiency causes hypothyroidism with
manifestations such as fatigue, weakness,
weight change ( weight gain), cold
intolerance, dry skin, constipation, and
hyperlipidemia. This symptoms are
virtually the same as those due to thyroid
disease.
20
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Symptoms and Signs

ACTH Deficiency
• Adrenocorticotropic hormone (ACTH)

deficiency results in diminished cortisol
secretion (see Adrenocortical
Hypofunction).
Symptoms include weakness, fatigues,
weight loss, and hypotension . Mild cortisol
deficiency may cause no symptoms at all.
• Cortisol deficiency due to ACTH deficiency,
unlike that due to primary adrenal disease,
do not cause hyperpigmentation.
21
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Symptoms and Signs

GH Deficiency
• Growth hormone (GH) deficiency in adulthood tends

to cause mild to moderate obesity. Adults who have
growth hormone deficiency have an increased
amount of fat tissue and decreased lean tissue ,
weak, and reduced cardiac output.
• Patients with growth hormone deficiency have lower
bone mineral density than normal people.
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Symptoms and Signs(D)

• Panhypopituitarism is the absence of all anterior
pituitary hormones. Besides the manifestations
noted above, patients with long-standing
hypopituitarism tend to have dry, pale, finely
textured skin. The face has fine wrinkles and an
apathetic countenance.
• The patients with pituitary tumors may have
headache 、visual impairment. This is the most
common symptom of a sella mass lesion .
23
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Laboratory Findings (A)

Biochemical indicator
• The fasting blood glucose may be low.

• Hyponatremia is often present.
• Hyperkalemia usually does not occur, since
aldosterone production is not affected.
24
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Laboratory Findings(B)
Hormone determine
• Plasma levels of sex steroids(testosterone

and estradiol) are low or low normal, as are
the serum gonadotropins as well.
• Elevated prolactin levels are found in
patients with prolactinoma, acromegaly, and
hypothalamic disease. But in most of
hypopituitarism ,the prolactin is low because
of lactotroph impairment .
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Laboratory Findings(B)
Hormone determine
•The free T4 level is low, and TSH is not

elevated.
•11-deoxycortisol or cortisol concentration
level is low
•ACTH level is low or normal in secondary
hypoadrenalism
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Laboratory Findings(C)
stimulating test
• Cosyntropin test in secondary

hypoadrenalism :
administration of cosyntropin (synthetic
ACTH1-24),0.25 mg (intramuscularly or
intravenously) usually causes serum cortisol
to rise to less than 20µg/dL by 30-60 minutes
after the injection.
27
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Laboratory Findings (D)

• The diagnosis of growth hormone (GH) deficiency is
difficult because of the pulsatile nature of the
hormone’s secretion.
• The insulin hypoglycemia test most accurately
diagnoses GH deficiency but is dangerous for
elderly of seizure prone patients.
• IGF-I levels may be low in GH deficiency, but there is
considerable overlap with normal .
28
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lmaging
• MRI provides the best visualization of

parasellar lesions.
• Tumor or other mass lesions also can be
found by MRI.
29
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Differential Diagnosis(A)
• Reversible physiologic hypogonadotropic
hypogonadism .The disease may occur during
any serious illness and with malnutrition.
The clinical situation , presence of normal
sex hair ,and normal adrenal and thyroid
function allow ready distinction from
hypopituitarism.
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Differential Diagnosis(B)
• Primary adrenal or thyroid insufficiency is
easily differentiated from pituitary
insufficiency, since serum ACTH and TSH
are not elevated in hypopituitarism.
• Severe illness causes functional suppression
of TSH and thyroxine. Glucocorticoids or
megestrol treatment reversibly suppresses
endogenous ACTH and cortisol secretion.
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Differential Diagnosis (C)

• Multiple endocrine deficiencies may involve
immunologic destruction of pancreatic islets,
thyroid, adrenals, and gonads (Schimdit
Syndrome ) ,but this disease have a elevated
pituitary hormone, the ACTH 、TSH 、FSH、
LH level are high, which is easy to
distinguish from hypopituitarism.
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Complications
• Patients with destructive lesions (eg, tumors)

may develop complications related to them or to
surgery or radiation therapy.
• Patients with untreated hypoadrenalism and a
stressful illness may become febrile and die in
shock and coma.
• Adults with growth hormone deficiency have
experienced an increased cardiovascular
morbidity
• Pituitary acute hemorrhage may occur in large
pituitary tumors, manifested by rapid loss of
vision, headache, and evidence of acute pituitary
failure .
33
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Treatment (A)
Principal
• The mainstay of substitution therapy for
pituitary insufficiency remains lifetime
hormone replacement.
• The therapy for cause of hypopituitarism. for
example: Transsphenoidal removal of
pituitary tumors will sometimes reverse
hypopituitarism .
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Treatment (B)
Replacement of adrenal cortex hormone
• Give hydrocortisone tablets, 15-25 mg/d orally in

divided doses. Most patients do well with 15 mg
in the morning and 5-10mg in the late afternoon.
A mineralocorticoid is rarely needed.
• Additional hydrocortisone must be given during
states of stress, eg, during infection, trauma, or
surgical procedures. For mild illness,
corticosteroid doses are doubled or tripled . For
trauma or surgical stress, hydrcocortisone is
givening doses of 50 mg intramuscularly or
intravenously every 6 hours and then reduced to
normal doses as the stress subsides.
35
PDFelement
Treatment
Replacement of adrenal cortex hormone
The type of corticosteroids and common usage
hydrocortisone cortisone prednisone
20mg 25mg 5mg
Their dosage are equivalency
36
PDFelement
Treatment
Replacement of thyroid and sex hormone
• Thyroid: Levothyroxine is given to correct
hypothyroidism only after the patient is assessed for
cortisol deficiency or is already receiving
glucocorticoids. The usual maintenance dose is
0.125 mg daily.
• Sex hormone replacement is discussed in the
section on male or female hypogonadism. The sex
hormone is recommended for fertility induction.
37
PDFelement
Treatment
• Human growth hormone is used for adult
with severe growth hormone deficiency and
child or adolescent with GH deficiency.
hGH (somatotropin) is synthesized by recom-
binant DNA techniques . Symptomatic adults with
severe growth hormone deficiency may be treated
with subcutaneous somatotropin injection starting at
a dosage of about 0.2 mg (0.6 IU) three times weekly
or daily. The dosage is increased until side effects
occur .
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Prognosis
• The prognosis depends on the primary cause .
1) Hypopituitarism resulting from a pituitary tumor may
be reversible with some drugs or with careful selective
resection of the tumor .
2) Patients can also recover from functional
hypopituitarism.
3)Most of patients need lifetime hormone replacement.
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PDFelement
Acute Hypopituitarism
Definition
• Acute hypopituitarism is the most common

emergency presentation of hypopituitarism
when patient is exposed to stress such as
infection、 surgery or dehydration and so
on ,which induce pituitary hormone need more ;
or when other reasons lead the pituitary function
impairment sharply .while it develops ,various
symptoms and signs of hypopituitarism become
profound, at last ,these patients may die in
shock and coma.
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PDFelement
clinical finding
• Hypotension /shock
• Weakness, apathy, confusion
• Nausea, vomitting, anorexia
• Dehydraton, hypovolemia,
• Water intoxication (the formation and excretion of urine
is difficult)
• Hyperthermia(>40℃) or hypothermia(<30℃)
• Hypoglycemia
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Treatment (A)
• Intravenous injection (IV) saline and glucose. At
first giving the 50% glucose treat hypoglycemia;
then , 10% Glucose and Sodium Chloride
Injection continues.
• Hydrocortisol 200-300mg per day if progress is
satisfactory and then taper to oral maintenance
dose by day 4 or 5.
• Amelioration Hyperthermia or hypothermia;
when body temperature increase to 35
℃,giving the levothyroxine.
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Treatment (B)
• Correction of remote causes. For
example :preventing and cure of infection .
• The patients with water intoxication must be
given cortisol, intravenous infusion or
intake water is confined.
• All drugs about sleeping and calm is
inhibited.
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PDFelement
Conclusion(A)
• Hypopituitarism is because of impairment of

anterior pituitary or hypothalamus, which
leads to hyposecretion of anterior pituitary
hormone, present itself with hypofunction of
adrenal gland thyroid gland sex gland and GH
deficiency .
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PDFelement
Conclusion(B)
• The patients with disease may feel weakness;

easy fatigability; lack of resistance to stress,
cold, and fasting, also have axillary 、pubic
hair loss 、sex
sex hypofunction 、weight
weight loss、
loss
cold intolerance and Low blood pressure.
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Conclusion(C)
• The laboratory findings of this disease is low

target gland hormone 、 low pituitary hormone
and weak or delayed responses to target gland
stimulating test.
• Most of these patient need target hormone
replacement treatment lifetime.
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PDFelement
Adrenal disease
The second hospital of Chongqing
medical university, Li Ke
PDFelement
The cross section and microstucture of adrenal

gland
Adrenal medulla Adrenal cortex
Medulla
Adrenaline
Little cortisol
Reticularis
Adrenal androgens
Fasciculata
Cortisol
Glomerulosa
Aldosterone
PDFelement
Function of adrenal cortex hormones
 Aldosterone---Mineralocorticoid
which take a important role to maintain the balance of
water and saline through the retention of sodium ion
and excretion of kalium ion.
 Adrenal androgens secreted by adrenal is rare, but
adrenal cancer can produce excessive androgens
and induce virilism of woman
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 Cortisol is the major human glucocorticoid.

 Glucocorticoids have several metabolic functions,
including the promotion of hepatic gluconeogenesis
and the peripheral catabolism of proteins.
 The cortisol affects many other tissues and functions
including the inflammatory response, the immune
response in lymphoid tissue.
PDFelement
The adrenal diseases divided into three

types :
1. Primary adrenocortical insufficiency
2. Cushing’s syndrome (hypercortisolism)
3. Primary hyperaldosteronism
PDFelement
• ADRENOCORTICAL
INSUFFCIENCY
(Addison’s Disease)
PDFelement
Main contents
• The causes of Addison’s Disease

• The clinical features of Addison’s Disease
• The laboratory features of Addison’s
Disease
• How to treat this disease?
• The adrenal crisis
PDFelement
Definition
 Addison's disease is an uncommon disorder caused by
destruction or dysfunction of the adrenal cortex, It is
characterized by chronic deficiency of cortisol, and/or
aldosterone, adrenal androgens.
 Primary adrenocortical insufficiency so-called
Addison's disease,is due to a problem with the
adrenal cortex itself, in which it does not produce
hormones.
 In secondary adrenocortical insufficiency, the adrenal
gland is intact, but the pituitary does not produce
ACTH, so that there is no stimulus of the adrenal
gland to secrete its hormones.
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Etiology (A)
 Idiopathic/autoimmune(~80%)
Autoimmune destruction of the adrenals is the
most common cause of Addison's disease in the
USA. It may occur alone or as part of a
polyglandular autoimmune (PGA) syndrome.
 Tuberculosis(~20%).
Tuberculosis was formerly a leading cause of
Addison's disease. The association is now
relatively rare in the USA but common in where
tuberculosis is more prevalent.
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Etiology (B)
 Adrenoleukodystrophy is an X linked peroxisomal
disorder causing accumulation of very long chain
fatty acids in the adrenal cortex. It may present at
any age and accounts for one-third of cases of
Addison's disease in boys.
 Bilateral adrenal hemorrhage may occur in
patients taking anticoagulants, during open heart
surgery, and during other major trauma.
 Other causes(~1%)
Fungal infection, AIDS,Neoplastic disease, and
Congenital disease
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Pathology
• Autoimmune adrenal insufficiency: There is early
lymphocytic infiltration of the adrenal cortex,
subsequently,the adrenal cortex is gradually destroyed
and the adrenals are small and atrophic. The cortex cells
of all the three zones are largely absent.
• Tuberculous Addison’s disease, the adrenal glands are
totally replaced by caseous necrosis with little or no
remaining cortices or medullary.
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Clinical Findings(A)
 Hyperpigmentation-the most distinctive physical

finding
Why? Primary insufficiency results in increased levels of
ACTH due to the feedback regulation of decreased
cortisol.Melanocyte-stimulating hormone(MSH) and ACTH
are cleaved from the same propeptide,so elevated ACTH
results in increased skin pigmentation.
PDFelement
Hyperpigmentation can be found in sun-exposed

areas and pressure points such as the elbows,
knees, toes and around the wrist. Abnormal
pigmentation should be suspected when it is
present on various mucosa (tongue, buccal),
hand creases,nipples, nail beds and navel.
PDFelement
mucosa (tongue, buccal),
Hand creases
nail
beds
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The characteristics of
hyperpigmentation
• Sun-exposed areas
• Mucous membranes
• Pressure points
• Original pigmentation points
PDFelement
Clinical Findings(B)
 The majority of these patients have gastrointestinal

symptoms. Anorexia is extremely common. Nausea,
vague abdominal discomfort,and vomiting occur more
frequently with progressive adrenal failure. Diarrhea
may be present but occurs less frequently.
 Hypotension is common but in many patients may
not be profound enough to suggest the diagnosis.
 Salt craving is a significant feature in about 20
percent of cases.
PDFelement
Clinical Findings(C)
 The fasting blood glucose level is within the low
normal range in most patients. It is unusual for a
patient with Addison’s disease to present with or have
symptomatic complaints of hypoglycemia.
 Weakness is always present and is accompanied by
fatigue and malaise.
 Weight loss is also very common, it is largely due to
tissue loss resulting from anorexia,but dehydration
also contributes.
 Other findings may include a small heart, hyperplasia
of lymphoid tissues, and sparse axillary and pubic
hair, and amenorrhea .
PDFelement
Clinical Findings(D)
PDFelement
Notice!!
• The clinical presentation depends on the rate

and degree of adrenocortical destruction.
• The most distinctive sign in chronic primary
adrenocortical insufficiency is hyperpigmentation
• How do the clinical symptoms occur?
(pathophysiology)
PDFelement
Pathophysiology
Hypoglycemia
ACTH Hyperpigmentation
Cortisol
Neutropenia
Hyponatremia
Retention
Aldosterone
of Na+ Hypovolemia
Hypotension
PDFelement
Laboratory Finding(A)
Basal levels of Urine or Plasma cortisol (Low or

normal)
Basal Plasma ACTH (>55pmol/ml,High)
ACTH stimulation test (Subnormal response)
Measuring the palsma ACTH will tell you whether it is

primary (high ACTH) or secondary(low or normal ACTH)
PDFelement
Laboratory Finding(A)
ACTH Stimulation Test methods and meaning
Rapid ACTH ST Three days ACTH ST
Methods Intravenous injection 25u Intravenous injection

ACTH in 30min,determin 25u ACTH in
the change of plasma 3days,determin the
cortisol after 30 min change of cortisol
plasma in 1、2 、3day
normal Increase 276~552nmol/L Gradually increase>2.5

times
meaning Diagnosis ,combined with Differentiate primary

ACTH can be used to from secondary
differentiate diagnosis adrenocortical
insufficiency
PDFelement
Laboratory Finding(B)
Ordinary Laboratory Features of Primary Adrenocortical Insufficiency
 Hyponatremia (90%)
 Hyperkalemia (65%)
 Azotemia
 Increased plasma renin activity
 Anemia and Lymphocytosis
 Hypoglycemia
 Hypercalcemia
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Essentials of Diagnosis(A)
• Weakness, weight loss;

• Anorexia ,nausea and vomiting, diarrhea;
abdominal pain (gastrointestinal
symptoms)
• Amenorrhea,sparse axillary hair(genital
system )
• Increased skin pigmentation;
• Hypotension, small heart;
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Essentials of Diagnosis(B)
• Serum sodium may be low; kalium, calcium, and urea

nitrogen may be elevated (electrolyte system )
• Neutropenia, mild anemia, eosinophilia, and relative
lymphocytosis may be present(hematological system )
• Plasma cortisol levels are low or fail to rise after
administration of ACTH.
• Plasma ACTH levels are elevated.
PDFelement
Differential diagnosis(A)
 Secondary adrenocortical insuffiency

The main difference :
1.There are other endocrine gland hypofunction
(hypothyroidism and hypogonadism)
2.ACTH is low
3.The hyperpigmentation of skin isn’t present.
• Chronic liver disease ( ACTH stimulation test --excessive
responses: significantly elevated plasma or urea cortisol )
• Other chronic disease
PDFelement
Diagnostic procedure
Suspected adrenalcortical insufficiency
Basal plasma cortisol and ACTH levels measurement

Fast ACTH stimulation test
Normal Cortisol Cortisol

ACTH ACTH
No response No response
Primary Secondary
Adrenalcortical Adrenalcortical
Insufficiency Insufficiency
PDFelement
Treatment(A)
• Treatment principle
Glucocorticoid replacement for all the
patients;
Dose of glucocorticoid increases in times of
stress and infection;
Mineralocorticoid replacement also be
required.
PDFelement
Treatment(B)
• Cortisol 8AM 20mg ,4PM10mg
• 9a-fluorocortisol 0.05~2mg qd
• Clinical follow-up
• Patient education plus identification
card
• Increased cortisol dosage during
“stress”
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Curative Effect
PDFelement
Adrenal Crisis
PDFelement
Definition
Adrenal Crisis is the most common emergency
presentation of primary adrenal insufficiency
when patient is exposed to stress such as
infection, surgery or dehydration and so on.
While it develops,various symptoms and signs
of Addison’s disease become profound.
PDFelement
Etiology(A)
• (1) Following stress.
• (2) Following sudden withdrawal of adrenocortical
hormone in patient with chronic insufficiency or in
patient with chronic insufficiency due to suppression
by exogenous glucocorticoids.
• (3) Following bilateral adrenalectomy or removal of a
functional adrenal tumor that had suppressed the
other adrenal.
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Etiology(B)
• (4) Following sudden destruction of the pituitary gland,or

when thyroid hormone is given to a patient with
hypoadrenalism.
• (5) Following injury to both adrenals.
The reason leads to not enough cortisol suddenly and

significantly can cause adrenal crisis .
PDFelement
Adrenal crisis occurs when:

• The adrenal gland is damaged (Addison's disease)
• The pituitary gland is injured (secondary adrenal
insufficiency) and it cannot release ACTH
• Adrenal insufficiency is not properly treated
PDFelement
Risk factors for adrenal crisis include:
• Dehydration
• Infection and other physical stress
• Injury to the adrenal or pituitary gland
• Stopping treatment with steroids such as
prednisone or hydrocortisone quickly or too early
• Surgery
• Trauma
PDFelement
Function of cortisol
Cortisol is a glucocorticoid that:

• Helps regulate glucose metabolism
• Holds back the immune response
• Is released as part of the body's response
to stress.
PDFelement
Clinical Findings
• Hypotension/shock,confusion or coma may be present

• Weakness,apathy,headache, lassitude
• Nausea, vomitting, anorexia,diarrhea, abdominal pain
• Dehydration, hypovolemia
• hyponatremia, hyperkalemia, Hypoglycemia
• Hyperthermia
PDFelement
Exams and Tests
• Cortisol level
• Fasting plasma glucose level
• Serum kalium
• Serum sodium
• Blood pressure
PDFelement
Treatment(Acute Phase)(A)
• If the diagnosis is suspected, draw a blood sample for

cortisol determination .
• Treat with hydrocortisone, 100-300 mg intravenously,
and saline immediately, without waiting for the results .
Briefly, give hydrocortisone 100mg intravenously
immediately, and continue intravenous infusions of 50-100
mg every 6 hours for the first day. Give the same amount
every 8 hours on the second day and then adjust the
dosage in view of the clinical picture.
Must be quick
PDFelement
Treatment(Acute Phase)(B)
• Correction of promoting factors

Since bacterial infection frequently promotes acute
adrenal crisis, broadspectrum antibiotics should be
administered empirically while waiting for the results
of initial cultures.
• IV saline and glucose
Hypoglycemia should be treated while serum
electrolytes,blood urea nitrogen, and creatinine are
monitored. Dehydraton, hypovolemia, hyponatremia
must be corrected by intravenous infusion saline and
volume replacement .
PDFelement
Treatment
(Convalescent Phase )
• When the patient is able to take food by mouth,
give oral hydrocortisone, 10-20 mg every 6 hours,
and reduce dosage to maintenance levels as
needed.
• Mineralocorticoid therapy is not needed when
large amounts of hydrocortisone are being given,
but as the dose is reduced it is usually necessary
to add fludrocortisone.
PDFelement
Prognosis
• Rapid treatment will usually be lifesaving.

However, acute adrenal insufficiency is
frequently unrecognized and untreated
since its manifestations mimic more
common conditions; lack of treatment
leads to shock that is unresponsive to
volume replacement and vasopressors,
resulting in death.
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PDFelement
CUSHING’S
SYNDROME
PDFelement
Definition
 Cushing’s syndrome refers to
the signs and symptoms caused by excess cortisol
production.This can be caused by taking
glucocorticoid drugs, or diseases that result in
excess cortisol, ACTH, or CRH levels
Harvey Cushing 1932
 Cushing’s disease refers to Cushing’s syndrome
caused by excess ACTH secretion by pituitary. It is
the most common cause of Cushing's syndrome.
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Etiology Exogenous vs. endogenous
 ⒈ Exogenous：the most common cause of
Cushing’s syndrome is exogenous administration of
glucocorticoids.
 ⒉ Endogenous: results from some disorder of the
body's own system of secreting cortisol.

PDFelement
Cause of Cushing’s syndrome

cause frequency
Endogenous
ACTH-dependent 85
Cushing’s disease 70
Ectopic ACTH syndrome 15
ACTH-independent 15
Adrenal adenoma 15
Adrenal carcinoma 5
Exogenous the most common cause
Iatrogenic
PDFelement
 Cushing's disease : is responsible for 70% of

endogenous Cushing's syndrome. It is caused
by ACTH excessive secretion by the pituitary.
And is usually caused by a pituitary adenoma,
esspacially micro-adenoma(diameter less than
< 5 millimetre).
It is at least five times more frequent in women
than men.
PDFelement
 About 15% is due to nonpituitary neoplasms(eg,

small-cell lung carcinoma ), which produce
excessive amounts of ectopic ACTH.
Tumors outside the normal pituitary-adrenal
system can produce ACTH (occasionally with
CRH) that affects the adrenal glands. This
etiology is called ectopic ACTH syndrome.
PDFelement
ACTH-independent Cushing’s syndrome
 The remaining 15% of endogenous Cushing’s

syndrome is unrelated to ACTH and are caused
by excessive cortisol secretion by an adrenal
tumor (adenoma or carcinoma) or rarely by
bilateral adrenal nodular hyperplasia.
PDFelement
Tumor in other tissues Tumor in other tissues

produces ectopic ACTH produces ectopic CRH Chornic
and lead to cortisol and lead to ACTH pharmacologic dosage
overscretion by adrenal. overscretion by pituitary. of glucocorticoid lead
The elevated cortisol The elevated ACTH to the iatrogenic
feedback inhibits ACTH simulates the adrenal Cushing’s syndrome.
production by pituitary. secrete excessive cortisol.
Hypothalamic-pituitary-
adrenal function in normalThe pathophysiology In of
patients with cortisol-
individual. The Cushing’s disease. secreting tumor, bilateral
hypothalamus produces Pituitary over secrete micronodular dysplasia and
CRH which induce ACTH ACTH, which stimulates bilateral ACTH-independent
secretion by pituitary. Andan elevated cortisolmicronodular hyperplasia,
then ACTH stimulates cortisol oversecretes by
production by adrenal.
cortisol produced by adrenal and feedback inhibits
adrenal. ACTH secretion by pituitary.
PDFelement
Clinical features and

Pathophysiology
PDFelement
Clinical Findings (A)

Central obesity
 Obesity is the most common physical finding,and
weight gain is usually the initial symptom, weight
gain is classically central, affecting mainly the
face, neck, trunk, and abdomen, with relative thin
extremities.
 Accumulation of fat in the face leads to the
typical “moon face”; Fat accumulation around
the neck is prominent in the supraclavicular and
dorsocervical fat pads; the fat deposition in the
latter is responsible for the “buffalo’s hump”.
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Central obesity with

protuberant abdomen
and thin extremities
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Clinical Findings (B)

Skin Changes
 Atrophy of the epidermis and its underlying
connective tissue leads to thinning and a
transparent appearance of the skin in
advanced cases. This also accounts for
plethoric appearance.
 Purple striae occur in 50-70 percent of these
patients,they are typically red to purple in
color, depressed below the skin surface
because of loss of underlying connective
tissue and wider than the pinkish-white striae
seen with pregnancy or rapid weight gain.
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Clinical Findings (B)

Skin Changes
 Easy bruisability with minimal trauma is present in 40
to 60 percent of patients.
 Minor wounds and abrasions frequently heal slowly and
poorly.
 Mucocutaneous fungal infections occur frequently .
 Hyperpigmentation of the skin occurs rarely in
patients with Cushing’s disease or adrenal tumors but
is more common in the ectopic ACTH syndrome.
 Hirsutism is present in 65 to 70 percent of female
patients because of hypersecretion of adrenal
androgens.
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Plethoric moon face
Buffalo hump
Skin infections
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Thighs and
abdomen purple
striae
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Hyperpigmentation in
ectopic ACTH syndrome
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Clinical Findings (D)

Hypertension
 Hypertension,a classic feature of

hypercortisolism, is present in 75-85
percent of these patients.
Hypertension and its complication
contribute greatly to morbidity and
mortality in Cushing’s syndrome.
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Clinical Findings (E)

Gonadal Dysfunction
 Gonadal dysfuntion is extremely common
because of elevated levels of androgens and
cortisol .
 Amenorrhea occurs in about 75 percent of
premenopausal females and is usually
accompanied by infertility. Male patients
frequently have decreased libido, and some
have decreased body hair and soft testes.
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Clinical Findings (F)

Psychological Disturbances.
 Psychological disturbances occur in about
two-thirds of these patients. The presentations
include emotional lability and increased
irritability. Increased anxiety,
depression,decreased concentration,and poor
memory also be present.
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Clinical Findings (H)

Muscle weakness and Osteoporosis
 Muscle weakness is frequently at the proximal

end and is usually most prominent in the lower
extremities.
 About 50 percent of the patients have clinical
obvious osteoporosis, back pain is an initial
complaint in 40 percent; Pathologic fractures
occur frequently in severe cases and most often
involve the ribs and vertebral bodies.
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Head of humerus Neck of femur Lumbar vertebra
Common positions of
Osteoporosis and Pathologic
fractures
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Clinical Findings
 Table1.Clinical features of Cushing’s Syndrome
Feature Percent with Feature

Central Obesity 94
Facial plethora 84
Hirsutism 82
Menstrual disorders 76
Hypertension 72
Muscular weakness 58
Back pain 58
Striae Acne 52
Psychological symptoms 40
Source: modified from Plotz et al.

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Clinical Findings
 TYPICAL FINDING：
Central obesity with a plethoric "moon
face", "buffalo’s hump", protuberant
abdomen, and thin extremities.
 Epidemiology:More common in female

(2~3:1)
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Major Clinical Features

 Weight gain, Central obesity
 Plethoric moon face
 Proximal muscle weakness
 Malaise
 Emotional lability
 amenorrhea
 Hirsutism
 Fragile,easily bruised skin
 Abdominal purple striae
 Osteoporosis
 Hypertension
 diabetes or impaired glucose tolerance
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 Diagnosis and differentiate

diagnosis
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Laboratory Findings
General Test (A)
 Glucose tolerance is impaired

 Leukocytosis with relative
granulocytosis and lymphopenia.
 Hypokalemia particularly in cases of
ectopic ACTH secretion .
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Laboratory Findings
Tests for Hypercortisolism (B)
 Plasma cortisol level is elevated and loss of
circadian rhythm
especially in midnight plasma cortisol level >7.5
ug/dL is indicative of Cushing's syndrome and
distinguishes it from other conditions associated
with a high urine free cortisol (pseudo-Cushing
states) .
 A 24-hour urine collection for free cortisol
and creatinine determine.
An increased 24-hour urine free cortisol (＞100 ug/24 hr)
helps confirm hypercortisolism (or free cortisol to
creatinine ratio > 95 mg cortisol/g creatinine).
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Circadian rhythm of cortisol secretion
Plasma cortisol levels peak at 6:00 AM, the second

peak appear at 4:00 PM, and the third peak appear
at around 0:00 AM
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Laboratory Findings
Tests for Hypercortisolism (A)
 The easiest screening test for hypercortisolism
--Small-dose Dexamethasone(DXM) Suppression Test
Normal: A low dose dexamethasone suppresses

cortisol in individuals with no pathology in
endogenous cortisol production.
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 Overnight DXM suppression Test:1 mg dexamethasone

is given orally at 12 PM and plasma cortisol measured at
about 8 AM in the next morning.
a cortisol level under 5 µg/dL excludes Cushing's
syndrome.
 Two-day DXM suppression Test: Giving dexamethasone,

0.5 mg orally every 6 hours for 48 hours. Urine or
plasma cortisol is measured in the next day.
The Urine or plasma cortisol is suppressed ＞50% in
normal.
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Laboratory Findings
Finding the cause of hypercortisolism (B)
 High-dose Dexamethasone Suppression Test

 8mg dexamethasone is given orally at 12 PM and
plasma cortisol measured at about 8 AM in the next
morning.
 Or give 2mg dexamethasone orally every 6 hours for 48
hours; Urine or plasma cortisol is measured in the next
day.
Urine or plasma cortisol decreased >50% indicate the
secretion of cortisol is suppressed .
 Adrenal tumor and ectopic ACTH neoplasms
can’t be inhibited.
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Laboratory Findings
Finding the cause of hypercortisolism (A)
 Once hypercortisolism is confirmed, a

baseline plasma ACTH is obtained.
ACTH level
Adrenal tumor
Pituitary or ectopic tumors

ACTH level below the normal range indicates a
adrenal tumor, whereas higher levels are produced
by pituitary or ectopic tumors.
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Laboratory Findings
Localizing Techniques (A)
 In ACTH-independent Cushing's syndrome, a
CT scan of the adrenals can localize the
adrenal tumor in most cases.
 In ACTH-dependent Cushing's syndrome, MRI
of the pituitary can demonstrate a pituitary
adenoma in about 50% of cases.
Why only find 50% cases in pituitary adenoma? Because some

pituitary tumor are very small.Some ACTH–dependent Cushing’s
syndrome is just hyperplasia of pituitary cells, of course, there isn’t
positive demonstration.
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Laboratory Findings
Localizing Techniques (B)
 Location of ectopic sources of ACTH is done

with CT scan of the chest and abdomen, with
special attention to the lungs (for carcinoid or
small-cell carcinomas), the thymus, the
pancreas, and the adrenals .
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We have learn the causes of Cushing’s

syndrome, the signs and symptoms,
laboratory findings.
Now let’s diagnose the disease……
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When a people show the

following signs, we
should suspect he may
have had Cushing’s
syndrome.
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Diagnosis
Essentials of Diagnosis (A)-clinical features
 Central obesity, muscle weakness,thin skin,

psychologic changes, hirsutism (cancer),
purple striae.
 Osteoporosis, hypertension, poor wound

healing.
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Diagnosis
Essentials of Diagnosis (B)-laboratory finding
If the laboratory examinations show the following
results, it further supports the diagnosis.
 Elevated plasma cortisol and urinary free

cortisol. Lack of normal suppression by
small-dose dexamethasone.
------Indicate hypercortisolism
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Etiological diagnosis
Characteristic of Cushing ’s disease
 There is hypersecretion of ACTH with bilateral

adrenocortical hyperplasia and hypersecretion of
cortisol.
 There is absent circadian rhythms of ACTH and

cortisol release.
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Characteristic of Ectopic ACTH Syndrome
 The ectopic ACTH syndrome is caused by ACTH

hypersecretion from nonpituitary tumors.
 There is hyperpigmentation in most of patients .
 The secretion of cortisol can’t be inhibited by

High-dose Dexamethasone Suppression Test.
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 Imaging Location
 X-ray showed light

enlargement of the right
mediastinum
 CT revealed a mass in
the right mediastinum
 PET found
concentration in the
same site.
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Characteristic of Cushing’s syndrome(Adrenal
tumor )
 There is a hyperscretion of cortisol with the
hyposecretion of ACTH.
 The secretion of cortisol can’t’ be inhibited by

High-dose Dexamethasone Suppression Test.
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Differential Diagnosis (A)-- Severe Obesity
 Patients with severe obesity may have

hypertension, impaired glucose tolerance,
amenorrhea, and abdominal striae.
Plasma cortisol or urine free cortisol is frequently
elevated, but with normal circadian rhythm.
Cortisol level is usually suppressed in Overnight
Small-dose Dexamethasone Suppression Test.
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Differential Diagnosis (B)-Pseudo-Cushing states
 Alcoholic patients can have hypercortisolism

and many clinical features of Cushing's
syndrome. The steroid dynamics revert to
normal after the cessation of alcohol intake.
 Depressed patients also have hypercortisolism
that can be nearly impossible to distinguish
biochemically from Cushing's syndrome but
without clinical signs of Cushing's syndrome.
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Plasma cortisol or urine free cortisol

level is elevated
Screening Test
Small-dose dexamethasone suppression test
High-dose
Diagnostic procedure dexamethasone
suppression test
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Cushing’s disease
Abdominal
CT scan
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Complications (A)
 Cushing's syndrome, if untreated, produces
serious morbidity and even death.
 The patient may suffer from any of the
complications of hypertension or of diabetes.
 Susceptibility to infections is increased .
 Compression fractures of the osteoporotic
spine and aseptic necrosis of the femoral
head may cause marked disability .
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Complications (B)
 Psychosis may occur.

 Following bilateral adrenalectomy for Cushing's
disease,a pituitary adenoma may enlarge
progressively, causing local destruction (eg,
visual field impairment) and hyperpigmentation;
this complication is known as Nelson's
syndrome.
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Nelson’s syndrome:
Hyperpigmentation
(flexural surfaces)
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 Treatment
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Treatment (A)-Cushing’s disease
 Treatment of Cushing's disease is currently

directed at the pituitary to control ACTH
hypersecretion; available methods include
microsurgery, various forms of radiation
therapy, and pharmacologic inhibition of
ACTH secretion. Hydrocortisone replacement
therapy is necessary in the process of
microsurgery.
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Treatment (B)
 Adrenal neoplasms secreting coitisol are resected
laparoscopically. The contralateral adrenal is suppressed,
so postoperative hydrocortisone replacement is required
until recovery occurs.
 Ectopic ACTH-secreting tumors should be surgically
resected. If that cannot be done, medical treatment with
ketoconazole or metyrapone (or both) may at least
suppress the hypercortisolism.
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Treatment of Cushing’s Syndrome

Removal of offending tumor.
If entire adrenal cortex is removed, daily administration
of adrenal corticosteroids is necessary.
Before surgery After surgery

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Thank you for your attention

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Hyperthyroidism
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Where to look for Thyroid ?
2
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Hypothalamic-pituitary-thyroid interrelationship
3
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Definition
 The term “thyrotoxicosis” refers to the clinical

manifestations associated with serum levels of
thyroxine (T4) or triiodothyroine (T3) that are
excessive for the individual.
4
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Definition
 Hyperthyroidism is the term for overactive tissue

within the thyroid gland causing an overproduction
of thyroid hormones. Hyperthyroidism is thus a
cause of thyrotoxicosis, the clinical condition of
increased thyroid hormones in the blood.
Hyperthyroidism and thyrotoxicosis are not
synonymous.
5
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The major causes for thyrotoxicosis
(1) increased occupancy of TSH receptors by TSI,

TSH, or hCG;
(2) autonomous overproduction of thyroid hormone
by thyroid nodules;
(3) increased release of thyroid hormone during
specific phases of thyroiditis;
(4) excessive thyroid hormone intake or ectopic
thyroid hormone formation.
6
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CAUSES OF THYROTOXICOSIS
Dependent on Increased Thyroid Hormone Production
Dependent on increased occupancy of the TSH receptor by:
Thyroid-stimulating immunoglobulin (TSI)
Graves' disease
Hashitoxicosis
Human chorionic gonadotropin (hCG)
Hydatiform mole
Choriocarcinoma
Thyroid-stimulating hormone (TSH)
TSH-producing pituitary tumor
Autonomous overproduction of thyroid hormone (independent of TSH)
Toxic adenoma (TSH receptor mutant)
Toxic multinodular goiter
Follicular cancer (rare)
Jod-Basedow effect (excess iodine-induced hyperthyroidism)
7
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CAUSES OF THYROTOXICOSIS
Independent of Increased Thyroid Hormone Production
Increased thyroid hormone release
Subacute granulomatous thyroiditis (painful)
Subacute lymphocytic thyroiditis (painless)
Nonthyroidal source of thyroid hormone
Thyrotoxicosis factitia
"Hamburger" thyrotoxicosis
Ectopic production by:
Ovarian teratoma (struma ovarii)
Metastasis of follicular cancer
8
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Etiology
1 Grave’s disease
 Autoimmune disease caused by antibodies to TSH
receptors
 Can be familial and associated with other autoimmune
diseases
2 Toxic multi-nodular goiter
 5% of all cases
 10 times more common in iodine deficient area
 Typically occurs in older than 40 with long standing goiter
9
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Etiology
3 Toxic adenoma
 More common in young patients
 Autonomically functioning nodule
10
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Etiology
4 Thyroiditis
Subacute
 Abrupt onset due to leakage of hormones
 Follows viral infection
 Resolves within eight months
 Can re-occur
Lymphatic and postpartum
 Transient inflammation
 Postpartum can occur in 5-10% cases in the first 3-6
months
 Transient hypothyroidism occurs before resolution
11
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Etiology
5 Treatment Induced Hyperthyroidism

 Iodine Induced
Excess iodine indirect
Exposure to radiographic contrast media
Medication
 Amiodarone Induced Thyroiditis
 Thyroid Hormone Induced
12
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Thyroid Hormone Induced

 Factitious hyperthyroidism in accidental or
intentional ingestion to lose weight
 Tumors
-Metastatic thyroid cancer
-Ovarian tumor that produces thyriod hormone
(struma ovarii)
-Trophoblastic tumor
-TSH secreting tumor
13
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GRAVES' DISEASE
 Graves' disease, also termed Basedow's or

Parry's disease, carries the hallmarks of excess
formation and secretion of thyroid hormone and
diffuse goiter. Additional characteristics include
exophthalmos, dermopathy (especially pretibial
myxedema), and rarely thyroid acropachy.
14
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GRAVES' DISEASE
The most common cause of thyrotoxicosis (50-60%).
Organ specific auto-immune disease
The most important autoantibody is
Thyroid Stimulating Immunoglobulin (TSI) or TSA
TSI acts as proxy to TSH and stimulates T4 and T3
Anti thyro peroxidase (anti-TPO) antibodies
Anti thyro globulin (anti-TG) Anti Microsomal and other
Autoimmune diseases - Pernicious Anemia, T1DM
RA, Gravis, Vitiligo, Adrenal insufficiency.
15
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Etiology and Pathogenesis
 Graves' disease is most likely an autoimmune

disorder with B lymphocytes producing
immunoglobulins, some of which bind to and
activate the TSH receptor, stimulating excess
thyroid growth and hormone secretion.
16
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Pathology
 The thyroid gland in Graves' disease enlarges

diffusely and contains increased vascularity.
 The parenchyma exhibits hypertrophy and
hyperplasia
 Infiltration by lymphocytes
 Severe thyrotoxicosis can lead to muscle atrophy
with muscle fiber degeneration, cardiac
hypertrophy, focal hepatic necrosis
17
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Clinical Symptoms
Depends on
 Age of patient
 Magnitude of hormonal excess
 Presence of co-morbid condition
18
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Clinical Symptoms
 Older patient presents with lack of clinical signs and
symptoms, which makes diagnosis more difficult
 Thyroid storm is a rare presentation, occurs after stressful

illness in under treated or untreated patient.
Characteristics
-Delirium -Dehydration
-Severe tachycardia -Vomiting
-Fever
-Diarrhea
19
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Common Symptoms
 Nervousness
 Anxiety
 Increased perspiration
 Heat intolerance
 Tremor
 Hyperactivity
 Palpitations
 Weight loss despite increased appetite
 Reduction in menstrual flow or oligo-menorrhea
20
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Common Signs
 Hyperactivity, Hyper kinesis
 Sinus tachycardia or atrial arrhythmia, AF, CHF
 Systolic hypertension, wide pulse pressure
 Warm, moist, soft and smooth skin-
skin- warm handshake
 Excessive perspiration, palmar erythema, Onycholysis
 Lid lag and stare (sympathetic over activity)
 Fine tremor of out stretched hands – format's sign
 Large muscle weakness, Diarrhea, Gynecomastia
21
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Clinical Exam of Thyroid
22
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Nervous and Psychiatric system

Psychiatric
 Hyperactivity
 Emotional lability
 Anxiety
 Decreased concentration
 Insomnia
Neuromuscular System
 Tremors-outstretched hand and tongue
 Hyperactive tendon reflexes
23
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Tremor
24
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Cardiac system
 Cardiovascular manifestations can be marked

 Increased cardiac output (due to increased oxygen
demand and increased cardiac contractibility.
 Sinus tachycardia
 Atrial fibrillation
 High output – heart failure output.
 Systolic hypertension, widened pulse pressure
25
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Cardiac system
 Sinus tachycardia
 Atrial fibrillation (A-fib) :10-20% of patients. More
common in elderly
 60% of A-fib will convert to normal sinus rhythm
with treatment to euthyroid
 Mitral valve problems
 LVH (left ventricular hypertrophy) and
cardiomyopathy
26
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Musculoskeletal system
 Muscles become atrophic and weak
 Myasthenia gravis: especially in Grave’s disease
 Hypokalemic periodic paralysis especially in Asian men
(cause is not known)
 Thyroid acropathy: clubbing of nails
 Bone resorption exceeds bone formation, resulting in
hypercalciuria and sometimes hypercalcemia.
 Long-standing hyperthyroidism may cause osteopenia.
27
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Musculoskeletal system
Clubbing
28
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Gastrointestinal system
 Food intake increases and some patients have insatiable
appetites.
 Hyperphagia (weight gain in younger patient)
 Anorexia- weight loss in elderly
 Weight loss is common.
 Hyperdefecation or diarrhea because of gastrointestinal
hypermotility
 Hyperdefecation
 Dysphagia
 Abnormal liver function tests
29
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Reproductive system
 Oligomenorrhea and amenorrhea

 Gynecomastia can occur in men
30
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Thyroid gland
 Enlargement of nodule(s)
31
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Thyroid gland
32
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Thyroid gland
33
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Thyroid gland
34
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Eyes
 The eye signs of thyrotoxicosis are most likely

mediated by an increased sympathetic tone and
include a widened distance between the upper
and lower lid, lid lag on upward gaze, and frequent
blinking. These signs do not indicate Graves'
ophthalmopathy and are not accompanied by
protrusion of the eyes.
35
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Eyes
 Infiltrative ophthalmopathy is part of Graves

disease
 Graves' ophthalmopathy that is clinically apparent
in only one eye occurs in 5 to 14% of patients.
 most of these patients have bilateral orbital
disease. (difference from eye’s cacinoma)
36
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Graves' ophthalmopathy
 Proptosis
 lid retraction (prevent complete closure of the eyes)
 keratitis and corneal ulceration
37
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38
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39
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40
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42
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43
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Skin
 Warm moist smooth skin

 Onycholysis:
 fine hair, hair loss
 excessive perspiration
44 Onycholysis
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Graves‘ skin change
45
Dermopathy
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Graves‘ skin change
 Dermopathy of Graves disease, an orange-peel

thickening of the pretibial areas, is rare.
46
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SPECIFIC FOR GRAVES' DISEASE.
 Autoimmune processes mediate the enlargement

of the thyroid gland, infiltrative ophthalmopathy,
dermopathy, and acropachy, thereby
distinguishing Graves' disease from other causes
of thyrotoxicosis.
47
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48
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Thyroid function tests
 establish whether there is hyperthyroidism

 show the cause of hyperthyroidism
49
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Thyroid function tests
 Serum T4 and free T4 concentration are increased

 Serum T3 and free T3 concentration are
also elevated
 Serum TSH, measured by the sensitive methods
now commonly available, is undetectable or
subnormal
 A normal or elevated TSH in a hyperthyroid patient
indicates TSH-induced hyperthyroidism
50
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Tests for etiology
 TSI is now available as a marker for active

Graves’ disease
51
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Tests for etiology
 Antiperoxidase (antimicrosomal) antibody in

Hashimoto's thyroiditis—a common cause of
HYPOthyroidism
 A radioactive iodine uptake test and thyroid scan
together characterizes or enables radiologists and
doctors to determine the cause of hyperthyroidism.
52
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A radioactive iodine uptake test
Normal v.s Graves

53
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Toxic Multinodular Goiter (TMG)

54
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Toxic Single Adenoma
55
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56
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Diagnosis and Differential Diagnosis
 In patients with severe Graves' disease showing

typical signs of thyrotoxicosis and autoimmune-
mediated manifestations such as ophthalmopathy,
the diagnosis is not difficult
 Measurement of free T4 , T3 , and TSH levels
constitutes a sufficient laboratory work-up
 In all patients with Graves' disease, T3 levels are
markedly elevated, and in most such patients free
T4 levels are elevated as well.
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 Anxiety states by themselves also lead to

irritability, tremor, weakness, tachycardia, and
weight loss. Thyroid hormone values are normal in
these conditions.
58
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 Subacute Thyroiditis
 The process may begin in one lobe and progress to involve
the other lobe in a few days. The sedimentation rate is
elevated; antithyroid antibodies are usually negative, and
the thyroid uptake of radioiodine is very low. A hyperthyroid
phase lasts for several weeks, followed by a transition
to a hypothyroid phase of several weeks and then
recovery.
 Thyroid tenderness is the hallmark of the disorder.
 Low thyroid uptake of 121I
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 Lymphocytic thyroiditis
 This disorder is responsible for a small percentage
of new cases currently. Usually a small firm goiter
is present, but the thyroid may not be enlarged or
may be up to three times the normal size.
 There is no thyroid tenderness.
 Low thyroid uptake of 121I
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Therapy
 The therapy for thyrotoxicosis is aimed at

decreasing thyroid hormone formation and
secretion.
 Three different therapeutic approaches are used:
(1) antithyroid drugs that inhibit the thyroid
peroxidase enzyme involved in thyroid hormone
formation, (2) radioactive iodine, and (3) surgery.
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ANTITHYROID DRUG THERAPY.

 Amelioration of thyrotoxic symptoms by decreasing thyroid
hormone formation
 PTU and methimazole (MMI), are the preferred initial
treatment options
 MMI administered once a day is effective, whereas PTU
must be given every 6 to 8 hours
 PTU inhibits peripheral conversion of T4 to T3
 Both compounds may exert a mild immunosuppressive
effect; a decrease in the level of TSI
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 PTU is most useful for patients with severe

thyrotoxicosis and for the treatment of Graves'
disease during pregnancy.
 Starting doses of 20 to 30 mg once daily are used.
Improvement of thyrotoxic symptoms, in general,
takes 2 to 3 weeks and can lag behind the
normalization of thyroid hormone values.
Euthyroidism can be achieved in 4 to 6 weeks.
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Imp. considerations Methimazole (MMI) Propylthiouracil(PTU)
Efficacy Very potent Potent
Duration of action Long acting BID/OD Short acting QID/TID
In pregnancy Contraindicated Safely can be given
Mechanism of action Iodination, Coupling Iodination, Coupling
Conversion of T4 to T3 No action Inhibits conversion
Rashes,
Adverse reactions Rashes, ↑Neutropenia
Neutropenia
Dosage 20 to 40 mg/ OD PO 100 to 150mg qid PO
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 Most patients can be maintained on low doses of

2.5 to 5 mg of MMI for 18 to 24 months.
 It appears that longer duration of antithyroid
therapy bodes well for patients staying euthyroid
after the medication is stopped.
 About half of patients undergo long-term remission
when the course of therapy is completed.
Relapses usually occur within the first year after
stopping therapy.
65
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SUPPORTIVE THERAPIES.
 ß-Adrenergic blocking agents help to provide relief

of symptoms such as tachycardia, tremor, anxiety,
and heat intolerance.
 ß-Adrenergic blocking agents have a small
inhibitory effect of T4 to T3 conversion.
 Patients with a history of asthma or congestive
heart failure should not receive ß-Adrenergic
blocking agents.
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RADIOACTIVE IODINE.
 RAI therapy (131 I) is used most frequently to treat

hyperthyroidism in adults in the United States
 RAI therapy is preferred for older patients with
moderate hyperthyroidism and thyroid
enlargement, for patients with a prior allergic or
toxic reaction to the antithyroid medication, and
when frequent medication intake cannot be
guaranteed.
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RADIOACTIVE IODINE.
 Before 131I administration, antithyroid drugs should

be stopped for 3 or 5 days.
 The incidence of hypothyroidism is approximately
10% to 20% after 1 year and increases at a rate of
2% to 4% each year, so that the cumulative
incidence is at least 50%.
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Surgical thyroidectomy
 Surgical removal of a large part of the thyroid (subtotal
thyroidectomy)
 Who is suitable for the surgical thyroidectomy?
 large obstructing glands
 glands containing nodules that are identified as
malignant or equivocal on fine-needle aspiration
 Pregnant women with severe hyperthyroidism
(thyroidectomy during the second trimester)
 toxic reactions to antithyroid drugs
 not candidates for antithyroid drugs and refuse
radioactive iodine
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 patients must be euthyroid before surgery is

undertaken.
 achieved by using PTU or MMI for approximately 6
weeks.
 potassium iodide can be administered daily for 7-
10 days before surgery
71
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 Complications of subtotal thyroidectomy:

 Hypothyroidism
 hypoparathyroidism
 recurrent laryngeal nerve paralysis
 hemorrhage
 wound infections, and keloids.
 50% of Grave’s ophthalmology can develop or
worsen
72
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Choice of therapy
 I prefer to use antithyroid drugs as the definitive

therapy for most patients, especially young and
middle-aged adults. Its main advantage is that the
therapy is reversible and does not destroy the
thyroid gland.
 For older patients and those with cardiovascular
disease or complicatinging disorders, 131I is the
preferred therapy
73
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Thyroid storm
 Clinical
 Thyroid storm is a dangerous condition of
decompensated thyrotoxicosis. The patient has
tachycardia, fever, agitation, restlessness or
psychosis, nausea, vomiting, and/or diarrhea. It
usually results from long-neglected severe
hyperthyroidism to which there is added a
complicating intercurrent illness, such as
gastroenteritis or pneumonia, or emergency
surgery.
74
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Treatment for thyroid storm

1. inhibit the release of hormone from the gland.(solution of
potassium iodide )
2. Inhibit the biosynthesis of thyroid hormones : Antithyroid
drugs in large doses (600 mg propylthiouracil or 60 mg
methimazole stat and half this dose q6h)
3. inhibit the sympathetic blockade : Propranolol in large oral
doses
4. antagonism to stress: hydrocortisone
5. symptomatic and supportive treatment: fluid replacement;
O2; temperature control; anti-infection
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76
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DIABETES MELLITUS
Zhang Lili zhanglili.jl@foxmail.com
Department of Endocrinology & Metabolism,
The 2nd hospital of Chongqing Medical
University
1 2
Global Projections for the Diabetes Epidemic:

Outlines for this lecture 2000--2030 (in millions)
2000
¾Definition of DM
¾Types of DM
¾Pathogenesis of DM
¾Diagnosis of DM
¾Therapy of DM World
2000 = 171 million
¾DKA 3
2030 = 366 million
Increase 213% 4
What is diabetes?
¾A group of metabolic diseases in
which a person has high blood
sugar
¾ either because the pancreas does Classification
not produce enough insulin
¾ because cells do not respond to
the insulin that is produced
5 6
1
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Anemia
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Definition
Classification
Signs and symptoms
Diagnosis
Treatment
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Definition
One of the most common hematological

problems affecting people of all ages,
is defined as the condition of lower level
of hemoglobin, and fewer RBCs in the
circulation.
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Hb
Lower count than the
normal value of the
Hct
people with the same
sex, same age, same
RBC
region
plain
Adult man Hb<120g/L,RBC<4.5X109/L or
HCT<0.42
Adult woman Hb<110g/L,RBC<4.0X109/L or
HCT<0.37
The most important one is the decrease of
hemoglobin
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the factors influencing normal

hemoglobin concentration
 Special population: The Hb of
infant、children、pregnant woman
lower than ordinary people
 altitude height: the Hb count of
those people in plateau area are
higher than those in horizontal
level.
 Plasma volume
Anemia is only symdrom ,not a disease
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Classification
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Pathophysiology of anemia
1. decreased production
Dietary deficiencies of iron,VB12,and folic acid.
Bone marrow damage as a result of chemotherapy,
or radiation.
Malignancies.
renal disease.
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2.Destruction-hemolysis
 immune mediated
 transfusion reaction, drugs
 infection: mycoplasma and viruses
 autoimmune: isolated or secondary to rheumatological
condition
 non-immune
 membrane abn: spherocytosis, PNH(paroxysmal nocturnal
hemoglobinuria)
 enzyme abn: G6PD deficiency
 hemoglobinopathies: sickle cell
 angiopathic: HUS, DIC,TTP
 splenomegaly
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3. Loss
 blood loss
 internal: joints, trauma
 external: GI, renal, menses
 Acute loss
chronic loss---IDA
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the degree of anemia
1) Mild Hb≥90g/L
2) Moderate Hb≥60g <90g/L
3) Severe Hb≥30g <60g/L
4) Extreme Hb<30g/L
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Morphologic Classification
type MCV(fl) MCH(pg) MCHC (%)

Macrocytic >100 > 32 31-35
Normocytic 80-100 26-32 31-35
Microcytic <80 <26 <31

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 macrocytic: Vit B12 and folate

deficiency, myelodysplastic
syndrom, liver disease.
 normocytic: acute blood loss,
hemolysis, aplastic anemia, uremia,
infiltration.
 microcytic: iron deficiency and
thalasemia
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microcytic macrocytic
hypochromic hyperchromic
+anisocytosis +anisocytosis
Normocytic
anisocytosis
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Signs and symptoms(1)

 Pallor
 Fatigue and exercise intolerance
 Dizziness and weakness
 Gastrointestinal complaints
 Decreased hemoglobin
 Bone pain and sternal tenderness
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Signs and symptoms(2)

once the acute volume loss exceeds
40% of the total blood volum
 Rapid pulse
 Shortness of breath
 Hypotension
 Difficulty sleeping
 Difficulty concentrating
 Menstrual problems; male impotence
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Physiological basis : decrease in

oxygen carrying capacity and thus
oxygen availability to tissues
The clinical manifestations depend on:
 The degree of anemia
 The speed of anemia occurred the acute blood loss will
show signs hypovolemia
 The body compensatory ability and hypoxia. anxiey,
confusion, hypotension .
 The degree of physical activity
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Diagnosis
1. Collect History
Etiology identification
the first exclude bleeding：black stool、
hematuria、menstrual abnormalities
then think of hemolysis：jaundice、 dark
brown urine
at last decreased production：fever,
petechiae
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 the patient should be questioned extensively

regarding the timing of the onset of
symptoms,transfusion history, past blood count
measurements, nutritional habits, alcohol intake,
and any associated symptoms of acute or
chronic illness such as weight loss, fever, or
night sweats.
 a few complaints are unique to specific types of
anemia. ( picophagia can be seen in iron-
deficient patient; complaints of a sore mouth
and difficulty swallowing are expressed by
patients with vitamin B12 and iron deficiency.)
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2.Physic examination
Observation
anemia
skin and mucous

membrane fingernail
dryness
Hypoxia symptoms and glossiness
sonitus memory Activity

and complexion
tolerance
sleeplessness low-grade
fever
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3.Lab test
 Blood routine examination: The Hb (hemoglobin) ,Hct
(hematocrit) and red blood cell count;
WBC,PLT,MCV.
 reticulocyte count: which is an essential component of
the CBC and plays a prominent role in initially
classifying any anemia. the reticulocyte production
index is an excellent measure of effective red blood
cell production. when a patient responds to anemia
with an increase in the reticulocyte index to levels
greater than 3 times normal, it strongly suggests that
the anemia is the result of hemolysis or hemorrhage.
Disease that interfere with marrow precursor
proliferation or maturation are characterized by lower
levels of effective red blood cell production.
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 bone marrow aspiration

a sample of marrow can easily be
obtained by needl aspirate or biopsy to
evaluate overall cellularity, the ratio of
erythroid to granulocytic precursors and
cellular morphology. the marrow
examination is of greatest value in patients
who fail to show an appropriate increase in
the reticulocyte production index in
response to aneamia.
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 Screening bleeding
bowel and urine inspection
 The proofs of RBC destruction
bilirubin、uroblinogen
 Testing of blood of lever of iron,VB12,and
folic acid
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Therapeutic princlples
 Etiological treatment
 Supportive treatment
component blood transfusion
Hemoglobin lower than 60g/L
–chronic anemia
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Aplastic Anemia
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Main points
 1.Aplastic anemia (AA) is a kind of acquired
disease.
 2.T cell extreme activation is the main
pathogenesis of AA.
 3.The non-typical AA should differentiate
with MDS.
 4.The treatment of AA should base on right
diagnosis.
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Definition
 Aplastic anemia is a bone-marrow failure
syndrome characterized by a marked reduction in
all hematopoietic precursors, and peripheral
pancytopenia resulting in anemia, infection and
bleeding.
 Incidence: 7.4 per million population
Eastern > Western country
idiopathic > secondary
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 Etiology
1. chemical factors: drugs (chloramphenicol),
chemicals (benzene)
2. radiation/physical factors : X orгray
3. biological factors: viral infection (hepatitis,
EB)
hepatitis associated aplastic anemia(HAAA)
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Pathogenesis
1 defect of the hematopoietic stem cells
2 abnormalities in the hematopoietic microenvironment
and growth cell factors
3 immunologically mediated damage to the
hematopoietic stem cells
Th1-Cell/Th2-Cell ↑, Th/Ts(CD4+/CD8+ )↓
Th1-cell produce IL-2, INFγ, TNFα,TNF↑
4 inherited factor
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Clinical Manifestations
 The manifestation of symptoms depends on
the extent of thrombocytopenia
(hemorrhagic symptoms), neutropenia
(bacterial infections, fever), and anemia
(pallor, fatigue, congestive heart failure,
tachycardia).
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Presentation of Anemia, Neutropenia and Thrombocytopenia
Hemorrhagic lesion of the gums in a patient with aplastic anemia

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Laboratory tests
 Peripheral Blood :Pancytopenia, Reticulocyte
count—decreased, normocytic anemia
 Bone Marrow: Bone marrow aspiration and
biopsy--hypocellular ,excessive fat tissue, Non-
hematopoietic cells increase
 Others: Cytogenesis, nuclear scan in bone marrow,
Flow cytometry, CD4+/CD8+ inversion, NAP ↑, EPO
↑
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外周三系减少，淋巴细胞比例升高
10
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Peripheral blood smear
SAA：morphology of RBC normal，

Only one lymphocyte
Platelet rare
NSAA： morphology of RBC normal

Some lymphocyte ,neutrophils
,platelets
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Bone marrow aspirate
"Watery" marrow can almost always be obtained. In

severe aplasia, the smear of the aspirated specimen
shows only residual lymphocytes and stromal cells; in
mild cases, the remaining hematopoietic cells show
"megaloblastoid" erythropoiesis. Megakaryocytes
are invariably greatly reduced and usually absent.
12
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Bone marrow biopsy

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DIAGNOSIS
 Is it AA
 SAA? Or NSAA?
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Diagnosis and Classification

AA
 history (anemia,fever,hemorrhage; no
enlargement of lyphonodus, liver, splen)
 pancytopenia, reticulocyte count—decreased
 BM hypocellular
 No splenomagaly
 exclusion of other diseases involved in
pancytopenia
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Hemolytic anemia
Complement mediated cytotoxic effect
Differential Diagnosis
Intravascular hemolysis
1. Marrow cellularity
Ham’(-), CD55/CD99
2. Marrow abnormal
aspirate morphilogy will usually
reveal disturbances in prolferation and
maturation.(agranular neutrophil and
 PNH megakaryocytes with from one to three
 MDS separate nuclei
 Acute leukemia
 Acute arrest of hematopoiesis
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 Classification
 NSAA: when ANC ﹥0.5x109/L, Plt ﹥
20x109/L, and reticulocyte﹥ 1%
 Severe AA: when ANC <0.5x109/L, Plt
<20x109/L, and reticulocyte < 1%
 Very severe AA: when neutrophic
count<0.2x109/L
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Treatment
 Supportive care
Transfusion therapy
Hamopoietic growth factors (G-
CSF,GM-CSF,)
Control of infection
Iron chelation therapy
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SUPPORTIVE TREATMENT
 Firstand most important, infection in the
patient with severe neutropenia must be
aggressively treated. Parenteral, broad-
spectrum antibiotics should be started
promptly
 Platelet and erythrocyte levels can be
maintained by transfusion. Candidates for
bone marrow transplantation should be
transfused sparingly and, of course, not with
blood products from a family member.
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 Treatment of non-SAA
Androgens
Cyclosporin A
Hemapoietic growth factors:G-CSF,GM-
CSF,EPO,IL-11
TCM (Traditional Chinese Medicine)
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 Treatment of SAA
 Allogenic hematopoietic stem cell transplantation
 - HLA-identical sibling donor
- Matched unrelated donor BMT
This treatment offers the best therapy for a young
patient with a fully histocompatible sibling donor.
Survival of patients younger than about 20 years
old after bone marrow transplantation is between
65% and 90%.
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 Immunosuppressive therapy
Most patients with aplastic anemia lack a suitable
marrow donor
 ATG(anti thymocyte globulin) or ALG(anti lymphocyte
globulin): purified monomeric IgG from hyperimune
horse/rabbit with human thymocyte/lymphocyte
 50% response
 70 -80% response (combined with cyclosporin)
 20-30% complete and durable recovery
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 response : after 8 to 12 weeks

 Complication:
MDS
also secondary solid tumors
leukemia
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AA
SAA NSAA
matched No donor
donor age>50
age<50
observe
Transplantation
Immunosuppression
Partial or No remission
complete
remission
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PROGNOSIS
 The natural course of untreated severe
aplastic anemia is rapid deterioration and
death resulting from infection or hemorrhage;
historically, survival in patients with severe
disease treated only with transfusions is
poor, probably about 20% at 1 year.
Fortunately, both transplantation of marrow
from a matched sibling donor and intensive
immunosuppressive therapies cure or
ameliorate aplastic anemia in the great
majority of patients.
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Prognosis
 The leading cause of death : bleeding in
brain, uncontrollable infection
 Untreated aplastic anemia : leads to rapid
death, typically within six months
 Allo-BMT 75~90% long term cure
 Immunosuppressive therapy: 5 year survival
60-80%
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Prevention
 Avoid to exposure to harmful substance
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Case discussion
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Case summary
1.Li**,37-year-old male patient.
2.He was admitted to our
hospital with the symptoms of
petechiae and ecchymosis of
the skin for 3days and fever for
1 day.
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3.3 days ago, The patient appeared

petechiae and ecchymosis on the skin of
the limbs with no obvious cause,no
gums bleeding, no epistaxis.1 days ago,
The patient appeared fever, with
maximum temperature of 38℃, no chills,
cough ,expectoration, abdominal pain,
diarrhea and so on, then he went to our
department for further treatment.
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4. Physical Examination:
no splenomegaly, no other
special
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The blood roution test showed:WBC

1.10* 10 ^ 9 / L, N 0.03* 10 ^ 9 / L, Hb 105
g/L, PLT 2 * 10 ^ 9 / L, no abnormal cells,
reti 0.005 * 10 ^ 12 / L, then the
hemoglobin decline progressively, with a
minimum of 65 g/L.HBV,HCV,EB,TORCH
were normal.
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2012.10.16
Bone
marrow
smear:
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2012.11.17
Bone
marrow
smear:
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2012.11.14
Bone
marrow
biopsy:
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5. Diagnosed of Severe aplastic

anemia,then did the allogeneic stem
cell transplants, the donor is his
brother, it is sible identical
transplantation
after the ASCT, review the blood
roution test: WBC 3.18* 10 ^ 9 / L, Hb
68g/L, PLT 355 * 10 ^ 9 / L,ret 0.164 * 10
^ 12 / L
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2012.12.19
Review the
bone
marrow
smear:
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Iron Deficiency Anemia

缺铁性贫血
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• A 1992 study,
conducted by India's
National Institute of
Nutrition, revealed iron
deficiency anemia
prevalences of 63%
among children 12-23
months of age and
67% among those 24-
35 months.
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• India has the highest prevalence of iron

deficiency anemia among women in the world,
including adolescents: 60-70 percent of Indian
adolescent girls are anemic
• Anemia among women can result in adverse
pregnancy outcomes and severe anemia can
lead to maternal deaths; reduced work
productivity and impaired physical capabilities
are other adverse outcomes.
• Adolescence, as a period of growth and
development, is considered the best time to
intervene, to assist in physical and mental
development, and to prevent later maternal
anemia.
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• Tanzania,
like most sub-Saharan
countries in Africa, suffers
from widespread iron-
deficiency anemia (IDA).
As many as 75% of
children under the age of
five years in Tanzania
suffer from IDA, with the
most severe cases among
children aged 6 to 24
months, according to the
Tanzania Demographic
and Household Survey.
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• Heinz Micronutrient Campaign Expands

to Africa for the First Time to Combat
Iron-Deficiency Anemia in Children
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Hemoglobin molecule
• Globin protein consisting of 4 polypeptide chains

(α2β2， α2δ2，α2γ2)
• One heme pigment attached to each polypeptide chain
– each heme contains porphyrin and Fe2+ that can combine reversibly
with one oxygen molecule
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General introduction
• functions of iron
component of
hemoglobin,
myoglobin ,iron-
containing enzymes,
involving in oxygen
transport and
oxidation/ reduction
reactions
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• Body iron distribution
total body iron
Adult males – 50mg/kg
Adult females – 40mg/kg
Distributions:
storage iron: ferritin,hemosiderin
transport iron: transferrin
functional iron: Hb, myoglobin, enzymes
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• stages of iron deficiency
– Decrease of stores (ferritin)
– Iron deficiency hematopoiesis
• Iron stores depleted with insufficient absorption to
counteract normal losses
• Leads to decreased hemotopoisis but no clinical anemia
– Iron deficiency anemia
• Hemoglobin falls
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• Definition
a microcytic and hypochromic anemia
resulting from low stores of iron.
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• Morbidity
IDA is reported to be the most common
nutritional deficiency in the world. It affects
20% to 50% of the world's population and
it is common in young children and
pregnant women.
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Metabolisms of iron
• Sources of iron
recycling Fe - dead cells to new cells
dietary Fe heme iron: animal source
non-heme iron :plant
source
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Iron in Foods
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Iron Contamination
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Metabolisms of iron
• Iron absorption
– Duodenum, jejunum
– absorbability
. Source of food
. Ionic iron
. Epithelium mediation
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Metabolisms of iron
• Transport
intestinal cells Fe2+
blood Fe3+ + transferrin
membrane of marrow RBC Fe3++ transferrin+ transferrin R.
Mitochondria Fe2++ porphyrin+ globin
Hemoglobin
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Metabolisms of iron
Several terms:
. Serum iron:
transferrin-associated ferric iron
.Total iron binding capacity (TIBC):
the total amout of transferrin that can combine with iron
. Percent of transferrin saturation:
= serum iron/TIBC X 100%
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Metabolisms of iron
• Storage
ferritin ,
hemosiderin
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Metabolisms of iron
• Sources
• absorption
• Transport
• Storage
• Excretion
1mg/d
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pathogenesis
• Decreased iron intake
– increased physiologic requirements for iron

– inadequate diet
– GI tract diseases
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pathogenesis
• Decreased iron intake
• Chronic blood loss
– gastrointestinal bleeding for males

– excessive menstrual flow for females
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Clinical manifestations
• Presentations of
– anemia symptoms
– symptoms of iron deficiency
– underlying disease
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Symptoms of anemia
• Fatigue
• Dizziness
• Headache
• Palpitation
• Dyspnea
• Lethargy
• Disturbances in menstruation
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Symptoms of iron deficiency

• Irritability
• Poor attention span
• Poor work performance
• Increased frequency of infection
• Defective structure and function of epithelial
tissue
• Pica
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Pica
• The habitual ingestion of unusual

substances
– earth, clay (geophagia)
– laundry starch (amylophagia)
– ice (pagophagia)
• Usually is a manifestation of iron deficiency

especially after hookworm infestation and is
relieved when the deficiency is treated
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• In infants: developmental delays;

behavioral disturbances
• In pregnant women: an increase in
preterm delivery ; an increase in
delivering a low-birth-weight child
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• glossitis
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• Koilonychia
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Laboratory findings
• Blood test
hemoglobin ↓
MCV ↓
Anisocytosis: red blood cells are of unequal size
Hypochromia:
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Laboratory findings
• Blood test
• Bone marrow test
– mild to moderate erythroid hyperplasia (25-

35%; N 16 – 18%)
– bone marrow showing absence of stainable
iron
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Laboratory findings
• Blood test
• Iron metabolism test
– serum iron concentration ↓
– serum ferritin levels ↓ (<12ug/l)
– total iron-binding capacity ↑
– saturation of transferrin ↓ (<15%)
– serum transferrin receptors ↑
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diagnosis
• IDA diagnosis
• Etiology diagnosis
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diagnosis
• Case
A 50 year old man comes to see you because
of fatigue and a change in bowel habit. He is
found to have a hemoglobin of 10.5 g/dl and
MCV of 76 fl . Stool : O.B. (+). Marrow
stainable iron test (-).He is healthy previously.
Question: Next ,which one is the most important test ?

A. Serum ferritin B. GI Barium
C. Colonoscopy D. abdominal CT scan
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Differential diagnosis
microcytic anemia
• Thalassemia
• Sideroblastic anemia
• Anemia of chronic disease
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treatment
• Treatment of the underlying disease
• Iron therapy
– Oral iron therapy
– Intramuscular iron therapy

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treatment
Oral iron therapy
• Preparations: ferrous sulfate tablets ,
ferrous gluconate
– iron absorption
• is enhanced: vitC, meat, orange juice, fish
• is inhibited:spinach, tea, milk, coffee
• Duration of treatment: 3 - 6 months
• Expected response: brisk reticulocytosis within

5 to 10 days
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treatment
Intramuscular iron therapy
• Indication: intolerance to oral iron
or disorder of GI tract
• Dosage: iron to be injected (mg)
= (15 - Hb/g%/) x body weight (kg) x 3
• Adverse effects: pain at the injection site,

anaphylactic reaction (5%)
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prevention
Iron-rich foods daily;

Health education;
Deworming, etc.
The Adolescent Girls Anemia Prevention Program at a Glance

(2000 – 2003)
• Objectives:
• 1. To increase number of daily meals adolescent girls eat from 2
meals to 3-4 meals
• 2. To encourage girls to consume iron rich foods on a daily basis
• 3. To encourage girls to consume vitamin C-rich foods in
combination with iron rich foods daily
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Hemolytic anemia
溶血性贫血
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definition
What is hemolytic anemia?
Hemolytic anemia is a disorder in which
the red blood cells are destroyed faster
than the bone marrow can produce them.
The term for destruction of red blood cells
is hemolysis.
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General characters
Anemia of increased destruction
• Shortened RBC survival
• Microcytic, or normocytic anemia
• Reticulocytosis-response to increase
• Increased indirect bilirubin
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pathogenesis
• Etiologies of increased destruction of RBC
membrane abnormalities
Intrinsic causes enzyme defects
abnormal hemoglobins
mechanical, chemical,
Extrinsic causes physical, inflammatory,
immune
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Pathogenesis
• Extravascular hemolysis
RBCs are removed from circulation by phagocytes, in the spleen,
liver, or bone marrow.
globin indirect direct
Hb porphyrin bilirubin liver bilirubin intestine stercobilinogen
Fe2+ kidney
urobilinogen
Pathophysiologic characters:
indirect bilirubin , stercobilinogen (+) , urobilinogen (+)
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Pathogenesis
• Intravascular hemolysis
free hemoglobin +haptoglobin liver metabolize
kidney urine excrete (hemoglobinuria)
reabsorb
hemosiderin accumulation
urine excrete (hemosiderinuria)
Pathophysiologic characters:
plasma free hemoglobin , haptoglobin ,
hemoglobinuria, hemosiderinuria
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Clinical features
• Acute (intravascular hemolysis)
acute onset, fever, chills,and lower back pain,
noticeable hemoglobinuria, heart failure, renal failure
• Chronic (extravascular hemolysis)

anemia, jaundice, enlargment of liver, spleen, Gall stones,
liver failure, etc.
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Laboratory testing
• Documenting RBC destruction
• Documenting marrow compensation
• Defining the etiology
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Diagnosis and differential diagnosis
• Diagnosis: history, clinical features, and

laboratory findings
• Differential diagnosis:
- Reticulocytosis
- jaundice
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treatment
• Etiological treatment
• Corticosteroids
• Blood transfusion (washed RBC)
• Spleenectomy
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Hereditary spherecytosis
Characters:
• Defect of RBC membrane ,
leading to spherecytosis
• Decreased deformability of cell
• Increased osmotic fragility
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Spherocytosis
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G6PD Deficiency
Characters
• Depressed functions of G6PD
• Decreased generation of
glutathione
• Hemolysis during oxidative stress
(infection, drugs, fava beans-
favism)
• Deformed Hb leading to Heinz
body formation
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Heinz body
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Immune hemolytic anemia

Characters
• Antibodies or complements combine with
RBC
• Macrophage recognize Fc receptor of Ig or
C3b, causing destruction of RBC
• Coombs test (+)
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Thalassemia
Demographics:
Found most frequently
in the Mediterranean,
Africa, Western and
Southeast Asia, India
and Burma
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Thalassemia
Hb Electrophoresis
• Alpha thalassemia: HbA, HbA2, HbF
• Beta thalassemia: HbA2, HbF
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Paroxysmal nocturnal
hemoglobinuria
• Clonal cell disorder
• Aquired deficit of GPI-associated protein
• Intravascular hemolysis classically at night
• Testing
Ham test(+)
Rouse test(+)
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Hemoglobinuria
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Thank you!
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Information On Hemophilia
• Hemophilia is the oldest known heredity
bleeding disorder.
• Hemophilia has been known for thousands
of years.
• People are born with Hemophilia and will
have it throughout their life.
• There are three types of hemophilia, A, B
and C, but hemophilia C is very rare.
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How boys are affected

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How girls may be affected

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Hemophilia A
• Hemophilia is a inherited bleeding disorder that is
caused by the lack or defect of the proteins that is
needed for blood to clot.
• It is caused by the lack of activity of the plasma
protein factor VIII which affects the clotting
property of blood.
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Blood Clotting
• Blood clotting is when
your blood turns from
a liquid to a solid,
which stops the
bleeding.
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Symptoms of Hemophilia A
•Bruising •Prolonged
bleeding
•Spontaneous bleeding •Blood in the

urine or stool
•Bleeding into joints •Gastrointestinal tract

with pain and swelling and urinary tract
hemorrhage
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Signs and Tests

• Normal bleeding time: test in which small
blood vessels close off to stop bleeding.
• Normal fibrinogen level tests the amount
of fibrinogen level in the blood.
• Test on partial thromboplastin time which
which measures the intrinsic clotting time
in plasma.
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Prevention of Hemophilia A
• Genetic counseling.
• Parents have the choice to terminate the

pregnancy.
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Hemophilia B
• Is also known as Christmas disease.
• Is also inherited blood clotting disease which is
caused by a deficiency of a blood plasma
protein called factor IX that affects the clotting
property of blood.
• Because of the lack of factor IX blood gets into
the joints and may leave people disabled.
• Hemophilia A is seven times more common than
hemophilia B.
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Symptoms of Hemophilia B
• Nose bleeds • Prolonged bleeding
• Bruising from cuts, tooth
• Spontaneous extraction, and
bleeding surgery
• Bleeding in joints • Excessive bleeding
following
• Blood in urine or circumcision
stool
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Signs and Tests

• Many of the tests and signs are the same
as hemophilia A.
• One tests that is different from the other
tests is the serum factor IX test. This is a
blood test that measures the activity of
factor IX.
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Prevention and How Bleeding

Can Be Stopped.
• Prevention for hemophilia B is also the
same as hemophilia A.
• R= rest.
• I= ice.
• C= compression.
• E= elevation.
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Treatment for Hemophilia

Hemophilia
1 Clotting factor
therapy
2 Transfusions
3 Exercise so the
muscle can
strengthen and
protect joints.
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Treatment for Hemophilia B

Hemophilia B
• Clotting factor therapy

• Transfusions
• Periodic infusion
• Exercise so the muscle
can strengthen and
protect joints.
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• 29、TT and TT are normal, PT is prolonged, which factor is

deficient?
• A、factor X
• B、factor VII
• C、factor VIII
• D、factor V
• E、factor II
• 30、–Which feature is commonly associated with chronic ITP?
• A、No sex difference
• B、Infection
• C、mild or moderate bleeding
• D、PLT count < 20×10^9/l
• E、Spontaneous remission is common
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Idiopathic( or Immune )
Thrombocytopenic purpura
(ITP)
特发性血小板减少性紫癜
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• Autoimmune disorder characterized by

autoantibody-induced platelet destruction.
• The 2 distinct clinical syndromes manifest
as an acute condition in children and a
chronic condition in adults.
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Etiology and pathogenesis

• Acute ITP
-Viruses associated
. Cross reactivity of anti-viral antibodies
with normal platelet glycoprotein to destroy
platelet.
. Direct effect on magakarycytes to
decrease the production of platelet.
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• Chronic ITP
-Autoimmune destruction
. Platelet-associated antibody,
PAIgG,PAIgM, PAIgA, PAC3,
. which bind to platelets’ IIb/IIIa
glycoprotein receptor
. Antibody-coated platelets are then
cleared from circulation by spleen.
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Incidence
• Incidence 1:10,000 of general population
• Peak incidence: 3-5y ( M/F ratio - 1:1 )
20-30y ( M/F ratio - 1:3 )
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Clinical manifestations
Acute ITP Chronic ITP
incidence Children (2-4y) Adults (15-40y)
Sex No difference M/F: 1:3
Infection Common Rare
onset Abrupt, <1 week Insidious, >6 months
Bleeding Severe, purpura, Mild or moderate,
Ecchymosis, Petechia,purpura,
Internal bleeding, mucosal bleeding,
spleenomagaly No No
Platelet count < 20 X 109/l (30-80) X 109/l
Spontaneous Common Rare

remission
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Laboratory evaluations
• Blood test
platelet acute: < 20 X 109/l
chronic: (30-80) X 109/l
Normal or megakarycyte
• Platelet associated antibody
PAIgG
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Diagnosis
• Bleeding history
• No spleenomegaly
• Platelet counts decrease
• Normal or increased megakarycytes
• PAIgG increase
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• thrombocytopenic purpura
Secondary, thrombotic,
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Treatment
the purpose of treatment of ITP is to bring

the platelet count to a stable, safe level.
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treatment
• Glucocorticoids
- Impaired clearance of antibody-coated platelets

by reticulo-endothelial system
- Inhibition of antibody production
- Stabilization of vessel wall
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Steroid responsive ( 10% )
Prednisone (1mg/kg) Steroid dependent

( 80% )
Steroid resistant ( 10% )

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treatment
• Glucocorticoids
• Immunosuppressive agents
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Treatment
Intravenous γ-globulin (IVIg)
Dose – high
Response rate – 85% (Plt>50,000)
Mode of action - impairs clearance of antibody-
coated
platelets by competitive binding to the Fc
receptor of
macrophages in the spleen
/
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Treatment
Indications for IVIg :
- Emergencies
- Preparation for splenectomy
- Refractory ITP
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treatment
• Glucocorticoids
• Immunosupressive agents
• Splenectomy
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Splenectomy – the treatment of choice for

all adult steroid-dependent and
steroid-resistant patients.
- Complete remission – 85%

- Low operative risk (esp. – with laparascopic approach)
- Major risk – overwhelming sepsis (< 1%)
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Leukemia
loushifeng
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Introduction
• Definition
History
1827 Velpeal
with his blood "like gruel”
1845 Benett ，Edinburg, England.
with "color and consistency of their blood";
Virchow ，Berlin,Germany
introduced leukemia from Greek meaning "white
blood"
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Introduction
• Definition
Leukemia is a group of clonal malignant
deseases developed form hematopoietic stem
cell or progenitor cell.
that lead to
Suppression of normal hematopoiesis
Infiltrations in outside of bonemarrow
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Introduction
• Classification
Acute Leukemia
Acute lymphocytic Leukemia（ALL）
Acute myelogenous Leukemia or Acute non-
lymphocytic Leukemia（AML，ANLL）
Chronic Leukemia
Chronic Granulocytic Leukemia（CGL，CML）
Chronic lymphocytic Leukemia（CLL）
Leukemia uncommon in clinic
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Introduction
• Incidence
• The total morbidity :
1.8
2.67/100 thousands 1.6
higher than the

1.4
1.2
chance to win a 1
0.8
lottery(1/400 0.6
0.4
thousands ) 0.2
0
AML ALL CLL
• 男：女=1.8：1
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Introduction
• Prognosis
100%
BMT
CHEMO
0 1 2 3 4 5 YEAR
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Introduction
• Etiology and Pathogenesis
Virus
ATLV HTLV-I HTLV-II
HTLV-III
Chemical substance
Bemzene poisoning
Ionizing radiation swell
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National Cancer Institute (NCI) researcher Robert Gallo

reports isolation of an AIDS virus he calls HTLV-III
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Introduction
• Etiology and Pathogenesis
Virus
ATLV HTLV-I HTLV-II
HTLV-III
Chemical substance
Benzene poisoning
Ionizing radiation
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Introduction
• Pathogenesis
Normal Stem cell
mutation
Leukemic stem cell
Progenitor cells
Blast cell
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Introduction
• 1)those that confer a proliferative or and
survival
KIT FLT3 ↑， NF-1 ↓
• 2) those that impair hematopoietic
differentiation and confer properties of
self-renewal
RUNX1-ETO,CBFB-SMMHC ,TEL-
RONX1 fusions mutation
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Introduction
• Properties of LSC:
self-renewal,quiescent,proliferation,multi-potentiality? ,
.
differentiation damaged
Immunophenotype of LSC :
AML CD34+CD38-CD71-CD90-CD117+ CD123+,HLA-
DR-;
CML CD34+CD38-
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Acute Leukemia
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Acute Leukemia
• Definition
characterized by a huge(massive)
accumulation of blastcells .the infiltration
of these blastcells result in ：
1 ）suppression of normal
hematopoiesis lead to
anemia,infection,bleeding
2 ）clinic manifestation related to
involvement of organs outside BM
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Acute Leukemia
• Classification：
1976 Morphologic Classifying by
International FAB cooperative group ，
1980 MIC ，Morphology, Immunology,
Cytogenetics
2001 WHO
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Acute Leukemia
• FAB classification
ALL：
L1:
lymphoblast cells are small,
usually < 12 um in
diameter .with scanty
cytoplasm and
inconspicuous(indistinctive)
nucleoli .more common in
children (approximately
85% of children cases of
AL).Prognosis is better .
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Acute Leukemia
ALL
L2:
lymphoblasts are larger in
size (>12um),have more
prominent nucleoli and
abundant cytoplasm .more
common in adult ,worse in
prognosis
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Acute Leukemia
ALL
L3:
identical
morphologically to
Burkitt’s
lymphoma.have
manifest deeply
blue(basophilia)
cytoplasm and
prominent vacuolation
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Acute Leukemia
• AML
M0 Acute myeloblastic leukemia,minimal differentiated
M1 Acute myeloblastic leukemia,without maturation
M2 Acute myeloblastic leukemia,with maturation
M3 Acute promyelocytic leukemia,hypergranular
M3v Acute promyelocytic leukemia,variant,microgranular
M4 Acute myelomonocytic leukemia
M4e0 Acute myelomonocytic leukemia with eosinophilia
M5a Acute monoblastic leukemia,poorly differentiated
M5b Acute monoblastic leukemia, differentiated
M6 Acute erythroleukemia
M7 Acute megakaryoblastic leukemia
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Acute Leukemia
• M0
minimal
differentiated
CD33,CD13+
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Acute Leukemia
• M1
myeloblast≥
90%
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Acute Leukemia
• M2
myeloblast
30~89%
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Acute Leukemia
• M3
Acute
promyelocytic
leukemia
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Acute Leukemia
• M3
Acute
promyelocytic
leukemia
microgranlular
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Acute Leukemia
• M4
Blast ≥30%
Monocyte>20%
CD14+
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Acute Leukemia
• M5
Monoblast+
Promonocyte
≥30%
CD14+
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Acute Leukemia
• M6 Acute
erythroleuke
mia
immature
erythrocyte>5
0%
blast ≥30%
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Acute Leukemia
• M7
megablast≥30%
CD41+,CD61+,
CD42+
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Acute Leukemia
干细胞（M0）
M1 M4 M5 M6 M7
myeloblast monoblast erythroblast MK
blasts
M2
M3 promyelocte PROmonocyte 早幼红

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Acute Leukemia
• FAB classification is simple and convenient ,but have
some shortage :
（1）It cannot avoid misdiagnosis since it rely on
the experience in morphology of observer
（2）It cannot identify the the further cell line the
leukemic cells origined from.
（3）It cannot distinguish M0、L2、M7、
biphenotypic leukemias, mixed lineage leukemias
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Acute Leukemia
• WHO 2001
ACUTE MYELOID LEUKAEMIAS
Acute myeloid leukaemias with recurrent
cytogenetic abnormalities
A M L with t(8;21)(q22;q22), ( A M L 1 / E TO ) 9 8 9 6 / 3
A M L with inv(16)(p13q22) or t(16;16)(p13;q22),
(CBF /MYH11) 9871/3
Acute promyelocytic leukaemia
( A M L with t(15;17)(q22;q12), ( P M L / R A R )
and variants) 9866/3
AML with 11q23 (MLL) abnormalitie
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Acute Leukemia
Acute myeloid leukaemia with
multilineage dysplasia 9895/3
with prior myelodysplastic syndrome
without prior myelodysplastic syndrome
Acute myeloid leukaemia and myelodysplastic
syndrome, therapy related 9920/3
Alkylating agent related
Topoisomerase II inhibitor-related
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Acute Leukemia
Acute myeloid leukaemia not otherwise categorised
Acute myeloid leukaemia,
minimally differentiated 9872/3
Acute myeloid leukaemia without maturation 9873/3
Acute myeloid leukaemia with maturation 9874/3
Acute myelomonocytic leukaemia 9867/3
Acute monoblastic and monocytic leukaemia 9891/3
Acute erythroid leukaemia 9840/3
Acute megakaryoblastic leukaemia 9910/3
Acute basophilic leukaemia 9870/3
Acute panmyelosis with myelofibrosis 9931/3
Myeloid sarcoma 9930/3
Acute leukaemia of ambiguous lineage
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Acute Leukemia
Clinic Manifestation
manifestation related to pancytopenia
（1）Infection
1）general feature：
2）infection site ：
3）Infective pathogens ：
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• associated with granulocytopenia and defect in immune system.

1）general feature：①fever T>38.5○C；②the local imflammation is
mild；③ progress rapidly，and easy to spread；④increased
opportunistic organisms infection.
2）infection site ：respiratory tract （nasal cavity,oral cavity,throat,lung
），digestive tract（esophagus,GI, anal areas），skin etc. oral
candidiasis
pneumonia ;dysphagia(difficult to swallow ) ;esophageal candidiasis,
perirectal abscesses
3）Infective pathogens ：Gram-negative and positive bacteria are
major pathogens of infection including —E.coli, Pseuduomonas-
aeruginosa, klebsiella pneumoniae，Staphylococcus aureus，
pneumonococcus。Fungus（candida,aspergillus,cryptococcus）
infections take more than 10~20%. Viraus,mycoplasma can also be
pathogens of infection.
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Acute Leukemia
• （2）Anemia
early of onset
develope progressively
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Acute Leukemia
（3）Bleeding
mainly caused by thrombocytopenia ,but also
related to dysfunction of blood vessel that
associated with infections and anemia.
petechial ecchymosis
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Acute Leukemia
manifestations caused by involvement of
organs outside BM
1）Peripheral WBC：
2）Enlargement of liver,spleen,and lymphonode:
3）Infiltration of oral mucous and gum :
4）Infiltration of skin:
Evection
nodule
sweet
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Acute Leukemia
5）CNS-L
common in ALL(50%),only 5~7% in AML
Many are asymptomatic.
present with intracranial hypertension颅内高压、stiff-neck颈强直、
papilledema视乳头水肿、nervous lesion第VI对cranial nerve lesion.
CNS-L can be diagnosed by determine of cerebrospinal fluid cytology.
6）Involvement of other organs:

Bone pain is common. eyes, lung, pleura, heart, pericardium, kidney can
also be involvement.
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Acute Leukemia
Leukostasis
The high number (>50000/mm3 specially M5)of
circulating bastcells increase blood viscosity and is
associated with small vessel leukoblastic
emboli ,resulting in leukostasis.
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Acute Leukemia
manifestatoins related to metabolic
abnormality：
hyperuricemia
hypercalcinemia
其他：
tumor lysis syndrome is characterized by the rapid
development of hyperuricemia,
hyperkalemia ,hyperphosphatemia and hypocalcemia etc.
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Acute Leukemia
Laboratory Findings
Blood Routine Examination
1） WBC count
2）leukemic cells can be found in 90%
patients
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Acute Leukemia
Bone Marrow Aspiration
1）Cellularity . found in 90% patients .
2）Leukemic cells ≥30% nonerythroid cells
3） Auer rods (spindle-shaped)can only be found in AML
3
Auer rods
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Acute Leukemia
Cytochemical Stain
Lymphoblast myeloblast monoblast
peroxydase - + ~ +++ ~+
nonspecific esterase - ~+ +
PAS(periodic aicd-Schiff) ： ++ - ~+
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Acute Leukemia
peroxydase Stain
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Acute Leukemia
Immunophenotypic Markers in AL
CD3 CD7 CD10 CD19 CD34 CD13 CD14 CD33 CD41,61 Gly A
CD2 CD20 CD22 CD15
B-CELL - - ++ ++ + - - - - - -
T-CELL ++ + + - - + - - - - - -
M0 - - - - ++ + +
M1~4 - - - - - ++ ++ +++ - - -
M6 - - - - - - - = - - ++
M7 - - - - + - - - +++ +++ -
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Immunophenotypic classification of ALL

Type Criteria Features
B >=2 makers:
D19,CD79a,CD22
Pro-B No more High WBC,CNS-L,MLL,poor
Common Additional CD10+ Low WBC,TEL/AML1,favorable
Pre -B Additional cyIgM+ High WBC,E2A/PBX1, favorable (intensive
chemotherapy)
Mature B Κ+,λ+,mIgM+ Common extramedullary, favorable
(intensive chemotherapy)
T cyCD3+/mCD3+
Pro-T CD7+
Pre-T CD2+/CD5 +/ CD8 +
Cortical -T CD1a+
Mature-T mCD3+, CD1a-
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Acute Leukemia
Cytogenetics
类型染色体基因
M3 t（15；17） PML-RARa
CML t（9；22）
ALL t（9；22） ABL-BCR
M2 t (8; 21) AML1-ETO
M4EO inv/del(16) CBFB-MYH11
L3 t (8 ;14) MYC IgH
M5 t/del(11) MLL-ENL
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Risk groups in AML according to

Cytogenetics
Risk group Karyotypic Feature

Favorable T(8;21);inv(16)/t(16;16);t(15;17)
Intermediate Mormal;-Y,del(7q);del(9q);t(9;11);
del(11q);+8,+11,+13,+21,
adverse Complex karyotype;inv(3)/t(3;3);-7;
t(6;9);t(6;11);t(11;19);-5;del(5q)
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Overall survival in adult patients

with AML
1.0
0.8
0.6
favorable
0.4
0.2
intermediate
advers
0.0
0 2 4 6 8 10 12 14
years
Blood 100:4325-4336
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Acute Leukemia
• AML with t（15；17）
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Acute Leukemia
• CML t（9；22）
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Acute Leukemia
Diagnosis
approach to diagnosis
If abnormality be found in blood routine test, specially
pancytopenia and immature cells ,the bonemarrow aspiration
and biopsy must be done
establish the diagnosis
blastcells≥30%(FAB) ,or ≥20% (WHO,2003)
classification would be correctly
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Acute Leukemia
• In fact ,blastcells≥30% never can be seen in any other disease
except Acute Leukemia.
Aplastic Anemia,
Infectious monocytosis ,
Infectious lymphocytosis etc.
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Acute Leukemia
Therapy
• 1865 Lissauer treated CML with Fowler
liquid with As in it.
• Farber treated ALL in children with MTX
(methotrexate)
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Acute Leukemia
• 1956 Thomas, a
firstman treated
leukemia with
bonemarrow
transplantation
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Acute Leukemia
Therapeutic principle
BMT
确诊 Induction therapy CR PBSCT long term survival
chemotheray
NR 复发relapse
按难治AL处理treat as refractory leukemia

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Acute Leukemia
• Support care
• high WBC
WBC>10,000/㎜3 oral administration of allopurinol
WBC>50,000/㎜3
• Infection
no fever T<101OF，prophylactic oral administration
Have feverT>101OF,broad spectrum antibiotics (eg
Imipenen) mus be used. If pneumonia has been confirmed or
temperature can not decreased in three days and blood
bacterial culture is negative ,amphotericin B would be used
empirically .
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Acute Leukemia
• Bleeding
platelet transfusion:
no signs of bleeding but PLT<10000/㎜3
signs of bleeding , PLT < 50000/ ㎜3
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Acute Leukemia
• Chemotherapy化学治疗：
Chemotherapeutic Protocol in ALL化疗方案：
(1).VP and VDP,VDLP
(2)High dose Ara-C(HDAC)
High dose methotrexate
（HDMTX）
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Acute Leukemia
• Chemotherapeutic protocols in AML
young adult
APL non-APL
ATRA+ anthracycline DA3+7

AS2O3
inv 16 or t(8;21) 中差
SCT high-dose allo-SCT

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Acute Leukemia
• M3(APL) induction remission therapy
(1)ALL-Trans- retinoic acid（ATRA）45mg/m2/day
P.O till CR,or addition of Idarubicin .no Ara-c needed.
(2)As2O3 20mg/day 30days
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Acute Leukemia
• induction of remission(non-APL)
DA(3+7) daunorubicin and cytarabine
D 45mg/m2 day 1,2,3
Ara-C 100mg/m2 day 1~7
CR Rate 60%
AML with multilineage dysplasia
FAT fludarabine and cytarabine and topotecan
CR Rate 80%
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Acute Leukemia
• consolidation therapy
(1)Patients with t(8:21), or inv(16)etc.
high-dose cytarabine ，at least three cycles ，cure rate of
60%–70%
(2)M3(APL) ATRA+D or ID As2O3
(3) chemotherapy or stem cell transplantation
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Acute Leukemia
Bonemarrow Transplantation
Indications
ALL
Relapsed/refractory;
CR2;
CR1,high risk,t(9;22),(4,11),+8,WBC>30~100;
AML
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mechanism of stem cell

transplantation
• 1、collection of stem cell
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transplantation
• 2、预处理(conditioning regimen)
TBI/Cy TBI 12 Gy 2Gy , -5、-4、-3、-2、-1、各类疾病

0 日
Cy 120mg/kg 60mg, -7、-6日
Bu/CY Bu 16mg/kg 4mg/kg, -8、-7、-6、-5日各类疾病

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transplantation
• 3、transfusion of stem cell ：
• 4、reconstitution of hematopoiesis and
immune
16
system
14
12
10
WBC
8
PLT
6
4
2
0
0
8
-4
-2
10
12
14
16
18
20
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Acute Leukemia
• 探索性治疗：
(1).Topoisomerase I Inhibitors: 9-
aminocamphothean
(2).MDR Reversing Agents:
cyclosporine,quinine, PSC-833
(3).Toxins Bound to Antibodies and RIT (CD33)
(4). Fludarabine
(5).Minitransplant
(6).Immunologic approachs: infusion of
allogeneic lymphocytes
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Acute Leukemia
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淋巴瘤
Lymphoma
重医二院娄世锋
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Thomas Hodgkin (1798-1866).

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Introduction
Definition
Lymphomas are immune malignant diseases
generated from lymph node or lymphatic tissues. They
constitute extremely heterogeneous diseases .
According to R-S cell can or not be found in tumor
tissues, lymphomas are classified as
Hodgkin’s disease(HD)
Non- Hodgkin lymphomas(NHL).

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Thomas Hodgkin (1798-1866). Dorothy Reed 1902

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Carl Sternberg
1898
1872~1935
Reed-sternberg cell
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Introduction
Definition
Histogenesis
In NHL,
common origin from mature lymphoid cell
First, they can derived from B and T cell line.
Second, they can derived from cells at different stages of

maturation.
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Introduction
Definition
Histogenesis
e.g Lymphoma derived from B cell lineage

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Introduction
paracotex DLBL? CD20,CIgM
Definition CD20,SIgM CD20,SIgM
B blast B immuneblast PC
PC
CD10,CD19,TDT
Naive Germinal center
Pre-B B cell MM
CD5,CD23,SIgMD
CD20 memory
Follicular Marginal zone
mantle
Eliminated
MCL FL,DLBL,BL
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Human B-cell malignancies

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Introduction
NK leukemia NK LYPHOMA
BLASTOID NK L.
NK-LGL
BOOD TISSUES
Immature
NKcell Hepatosplenic
CD8+γδ
Mucosae,skin
,spleen cutaneus γ/δ
L Stem cell
CD4+αβ CD4+αβ CD4+αβ MF
Precursor T L.N paracortex BLOOD
CD8+αβ CD8+αβ CD8+αβ SPTCL

ETCL
TALL TPLL PTCL,ALCL, T-LGL

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Introduction
Definition
Histogenesis
• In most cases of HD, molecular genetic
studies support an origin of the RS cell form
“crippled” germinal center B cell .In 10 -
15% cases of HD,RS cell express T cell
differentiation antigen (CD3 )
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Introduction
Definition
It must be outlined that lymphomas are extremely
heterogeneous diseases including different

pathological classification and grouping ,so patients
with lymphoma may be remarkably differ from each
other with their difference of clinic manifestation and
prognoses.
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Introduction
Epidemiology
Incidence
20 30 40 50 60 age
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Introduction
Epidemiology
Incidence：
HD：take about 10% of lymphoma in CHINA
NHL：3/100000 in Shanghai，6/100000 Hongkong ，

10/100000 in USA，1~11/100000 in other countries ，
male evidently more than female。
prominently increased in recent years ,16/100000 in

USA in 2002.
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Introduction
Epidemiology
Mortality rate
9.10
8.10
7.10
6.10
5.10
4.10
3.10
2.10
1.10
0.10
10 20 30 40 50 60 70 80
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Introduction
Epidemiology
The etiology of HD is uncertain. Both genetic susceptibility

and infectious agents especially EBV are considered.
In most cases of NHL is a sporadic disease without specific
etiologic factors. Professions with exposure to chemical
substance , Immunosuppression ,some infectious agents may
increase the risk to develop NHL.
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Lymphomas associated with infectious agents

Nasal, cutaneous and systemic NK/T-cell lymphomas EBV
Adult T-cell leukemia/lymphoma HTLV1
Marginal zone lymphomas H pylori, B burgdorferi, C jejuni, Hepatitis C, and others
Primary effusion lymphoma, LBCL associated with multicentric HHV-8/ KSHV
CD
Plasmablastic, Burkitt, DLBCL, CHL EBV (subset of cases)
Lymphomas with deregulation of apoptosis and survival
pathways
Follicular lymphoma BCL2/IGH@
MALT lymphomas API2/MALT1 and variants
Lymphomas with deregulation of the cell cycle
Mantle cell lymphoma CCND1/IGH@
Burkitt's lymphoma MYC/IGH@ and variants
Lymphomas with deregulation of cell signaling or
transcriptional regulation
Anaplastic large cell lymphoma NPM/ALK and variants
Diffuse large B-cell lymphomas BCL6, NFB, Stat6
Lymphomas associated with host susceptibility factors,
congenital or acquired
Enteropathy-associated T-cell lymphoma Genetics, gliadin allergy
Extranodal and systemic EBV + T/NK cell lymphomas Genetics, host response to EBV
Hepatosplenic T-cell lymphoma Immunosuppression combined with chronic antigenic stimulation
Lymphomatoid granulomatosis Partial immune dysfunction and EBV

Burkitt lymphoma Polyclonal B-cell activation with or without immunosuppression
(malaria, HIV)
Posttransplantation and other iatrogenic lymphoproliferative Iatrogenic immunosuppression
disorders
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General Mechanism of Lymphomagenesis
The pathogenesis of lymphoma is a highly complex

process involving genetic alterations in the tumer clone
itself as well as biological alterations in the host.
Four main mechanisms are described as follows:

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Accumulation of gene alteration in the tumor genome
Infection of the tumor clone by an oncogenic virus
Stimulation and selection of tumor cell by an antigen
Immunodeficiency of the host

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•Activation of proto-oncogenes by chromosmal

tranlocation
e.g t(14;18),t(18;22) Bcl-2 apoptosis
•Other mechanism of proto-oncogenes alteration

e.g proto-oncogenes amplification (myc)
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EBV:EB病毒与NHL有关（13.95%,上海）,与
EBV:EB NHL 13.95%, ,
HD也有关（40%，上海）。在非洲，EB病毒见
于90%的Burkitt淋巴瘤
HHV-8:human herpesvirus-8
HTLV-I:成人T细胞白血病（Japan）
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•Mutations of Ig gene usually are driven by Ag

•Biased usage of Ig gene.
•Ag receptors expressed by NHL cell.
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Immunodeficiency of the host
AIDS ， BMT ， APBSCT, hereditary

Immunodeficiency and other disease with
Immunodeficiency。
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Classification in Pathology
Hodgkin Disease RS cells can be found
Nodular sclerosis
Lymphocyte predominance
Lymphocyte depletion
Mixed cellularity
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follicular lymphoma (FL)
• In 1941, Edward A. Gall and Tracy B. Mallory,

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a new classification of Hodgkin disease
in 1966, Lukes and Butler

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Rappaport classification
1956
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Classification in Pathology
Non-Hodgkin Lymphoma
NHL: Revised European American lymphoma

classification
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Revised European-American
Classification of Lymphoid
Neoplasms (REAL classification）
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NHL: Revised European

American lymphoma classification
B cell T cell
Precursor B-cell neoplasm
Precursor T-cell neoplasm
Precursor B lymphoblastic leukemia/lymphoma
Peripheral B-cell neoplasm Precursor T lymphoblastic
B-CLL/prolymphocytic leukemia/small lymphocytic leukemia/lymphoma
lymphoma Peripheral T-cell and NK cell neoplasm
Lymphoplasmacytoid lymphoma/immunocytoma T-CLL/prolymphocytic leukemia
Mantle cell lymphoma LGL
Follicle center lymphoma, follicular Sezary Syndrome
Marginal zone B-cell lymphoma
Peripheral T-cell lymphoma, unspecified
Provisional entity: splenic marginal zone lymphoma
HCL Angioimmunoblastic T-cell lymphoma
Plasmacytoma / myeloma Angiocentric lymphoma
Diffuse large B cell lymphoma Intestinal T-cell lymphoma
Subtype: primary mediastinal (thymic) B-cell ATL
lymphoma Anaplastic large cell lymphoma
Burkitt lymphoma Provisional: Anaplastic large cell lymphoma,
Provisional entity: high grade B cell lymphoma,
Burkitt-like Hodgkin like
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WHO classification of the mature B-cell, T-cell, and NK-cell neoplasms (2008)
Mature B-cell neoplasms
Chronic lymphocytic leukemia/small lymphocytic lymphoma Mature T-cell and NK-cell neoplasms
T-cell prolymphocytic leukemia
B-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia
Splenic marginal zone lymphoma Chronic lymphoproliferative disorder of NK cells*
Hairy cell leukemia Aggressive NK cell leukemia
Splenic lymphoma/leukemia, unclassifiable* Systemic EBV+ T-cell lymphoproliferative disease of childhood
Splenic diffuse red pulp small B-cell lymphoma*
Hairy cell leukemia-variant* Hydroa vacciniforme-like lymphoma
Lymphoplasmacytic lymphoma Adult T-cell leukemia/lymphoma
Waldenström macroglobulinemia Extranodal NK/T-cell lymphoma, nasal type
Heavy chain diseases Enteropathy-associated T-cell lymphoma
Alpha heavy chain disease Hepatosplenic T-cell lymphoma
Gamma heavy chain disease Subcutaneous panniculitis-like T-cell lymphoma
Mu heavy chain disease Mycosis fungoides
Plasma cell myeloma Sézary syndrome
Solitary plasmacytoma of bone Primary cutaneous CD30+ T-cell lymphoproliferative disorders
Extraosseous plasmacytoma
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue Lymphomatoid papulosis
Primary cutaneous anaplastic large cell lymphoma
(MALT lymphoma) Primary cutaneous gamma-delta T-cell lymphoma
Nodal marginal zone lymphoma Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell
Pediatric nodal marginal zone lymphoma* lymphoma*
Follicular lymphoma Primary cutaneous CD4+ small/medium T-cell lymphoma*
Pediatric follicular lymphoma* Peripheral T-cell lymphoma, NOS
Primary cutaneous follicle center lymphoma Angioimmunoblastic T-cell lymphoma
Mantle cell lymphoma Anaplastic large cell lymphoma, ALK+
Diffuse large B-cell lymphoma (DLBCL), NOS Anaplastic large cell lymphoma, ALK–*
T-cell/histiocyte rich large B-cell lymphoma Hodgkin lymphoma
Primary DLBCL of the CNS Nodular lymphocyte-predominant Hodgkin lymphoma
Primary cutaneous DLBCL, leg type Classical Hodgkin lymphoma
EBV+ DLBCL of the elderly* Nodular sclerosis classical Hodgkin lymphoma
DLBCL associated with chronic inflammation Lymphocyte-rich classical Hodgkin lymphoma
Lymphomatoid granulomatosis Mixed cellularity classical Hodgkin lymphoma
Primary mediastinal (thymic) large B-cell lymphoma Lymphocyte-depleted classical Hodgkin lymphoma
Intravascular large B-cell lymphoma Posttransplantation lymphoproliferative disorders (PTLD)
ALK+ large B-cell lymphoma Early lesions
Plasmablastic lymphoma Plasmacytic hyperplasia
Large B-cell lymphoma arising in HHV8-associated multicentric Castleman Infectious mononucleosis-like PTLD
disease Polymorphic PTLD
Primary effusion lymphoma Monomorphic PTLD (B- and T/NK-cell types)
Burkitt lymphoma Classical Hodgkin lymphoma type PTLD
B-cell lymphoma, unclassifiable, with features intermediate between diffuse
large B-cell lymphoma and Burkitt lymphoma
B-cell lymphoma, unclassifiable, with features intermediate between diffuse
large B-cell lymphoma and classical Hodgkin lymphoma
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Clinical Manifestation
Hodgkin Disease
• Enlarged Lymph node: usually firm and rubbery and often

bulky. Involvement includes supraclavicular ,cervical,axillary.
•Regional complication results in compression
•Associated systemic symptoms
fever >38.5C ; night sweats; weight loss>10% body
weight
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在美国，低恶性度淋巴瘤占40%，但在我国，仅占10%。
Indolent lymphoma ：
（ 1 ） present with widespread central and peripheral
adenopathy ,but progress slowly
（2）lymphonode can be moving ,hardness like rubber.
（3）blood,BM,liver usually be involved
（4）the function of BM,liver usually are normal
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Aggressive ：
symptomatic at diagnosis ;
short disease history;
enlarging lymph node ;
obstructive symptoms;
Extranodal involvement;
deep mass bigger than 10 cm;
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Very aggressive
Burkitt and lymphoblastic lymphoma.they are
common in young adult and children ;rapidly
enlarging mass in abdominal ,blood and BM
involvement are common, LDH level is extremely
high (Burkitt);or rapidly enlarging mass in
mediastinal area (lymphoblastic lymphoma).
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Diagnosis
Diagnosis
depend on biopsy of lymphonode or lesions are involved.
Following examination helpful to staging
routine examination：patient history病史、physical

examination 体格检查、 hemogram 血象、 Ig 、
liver\kidney test 肝、肾功、X-ray、腹部和盆腔
CT 。 aspirate of BM or cerobrospinal fluid
cytology if necessary
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Diagnosis 分期（staging）
Staging
I Involvement of a single lymph node region or structure
II Involvement of tow or more lymph node region on same
side of the diaphragm
III Involvement of tow or more lymph node region on both
side of the diaphragm
IV Involvement of one or more extranodal site
A：asymptomaitic B：fever、sweating
X：huge tumor mass ，>10cm
E： extranodal site near only one lymph node region
CS：clinic staging PS：pathologic staging
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Treatment
一、very aggressive NHL
1、 alkalinize urine (sodium bicarbonate )
2、化疗：hyper-CVAD
cy 300mg/m2 iv 3hr g12h×3day
mesna 600mg/m2 iv 24hr×3day (cy前1hr开始)
after last dose of CY最后一剂CY后
Adr 25mg/m2 iv 24hr×2day (adriamycin)

VCR 1mg iv 24hr×2day
Decadron 40mg/day po day1-4,11-14
G-CSF 5ug/kg adr 后 till day 21 or WBC>30,000
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Treatment
二、 aggressive NHL
CHOP方案是标准治疗方案，其它治疗方案常常与它
作比较。但治疗前应对患者进行疗效预测。用肿瘤积
分（ tumor score ）、国际预后指数（ International
Prognostic Index,IPI）均可预测疗效。
CHOP（21-28 days a course ）
CY 750mg/m2 iv day 1
Adr 50mg/m2 iv day 1
VCR 1.4mg/m2 iv day 1
P 100mg po day 1-5
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Treatment
肿瘤积分（tumor score）：下列各项各一分
1）全身症状；
2）III或IV期；
3）任何肿块>7厘米；
4）LDH >1.10正常水平;
5）β2-微球蛋白>1.5正常水平。
肿瘤积分>3，预后差。如<3则CHOP方案无病生成率可达
80%。所以对中恶度NHL的治疗>2应使用探索性方案。
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Treatment
Indolent NHL
•10-20%病变局限（I、II期）可单用放疗。
•进展期病变（III、IV期）。其治疗现仍有争议。
•50%患者中于诊断后8年内从一种惰性形式转化
为侵袭性肿瘤。
•Fludarabine based protocol

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Treatment
HSCT
AutoHSCT
All0-HSCT
Rituximab
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多发性骨髓瘤
Multiple Myeloma
第二临床学院娄世锋
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概述
Express Marginal zone

PC
surface Ig
receptor Naive Germinal center
Pre-B B cell
memory
Follicular
mantle
Eliminated
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概述
多发性骨髓瘤是起源于B细
胞的恶性肿瘤。
 dystroied bone
 monoclonal
inmmugolubin
Plasma cell increased
in bone marrow
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病因及流行病学
• Unknown etiology
• Incidence 4/10万，median age
65岁
65
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发病机制
 瘤细胞特征
形态特征
Cig+、CD38+、PCA-1+
少部分表达CD10、HLA-
DR、CD20
起源
微环境
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发病机制
 粘附分子 VLA-4和VCAM-1
 细胞因子 IL-6 IL-6
 癌基因 c-myc，H-ras，bcl-2
表达增强。P53点突变。
VLA-4
VCAM-1
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manifestations
Bone pain
Dystroied bone
高钙血症
anemia Bonemarrow IL-6
myeloma cells Kidney damage
高粘滞血症
infection Immune M
defieciency protien 淀粉样变
amyloidosis
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Laboratory findings
• Peripheral blood：anemia，ESR,plasma cell，
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Laboratory findings
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Laboratory findings
• bone marrow：典型病例骨髓浆细胞异常增生并伴质的
改变（瘤细胞），浆细胞多在10%以上，但可从
<5%~100%。有时形态类似正常浆细胞。
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实验室检查
• 蛋白电泳：M protein。IgG(52%)IgA(21%)
IgD(2%),无M蛋白(7%)
• β2微球蛋白及LDH：
• 其他：proteinuria，Ben Jos protein
（+）；BUN、Cr；hypercalcemia
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Laboratory findings
• X-ray：osteoporosis；Dissolved bone
lesions ；fracture of bone
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• 诊断方法：bone
pain;fracture;proteinuria;kidney
damage ;anemia;hyperimmugolubinemia;
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• Establish diagnosis：
1、plasma cell in bone marrow
2、M protien
3、bone lesion or osteoporosis
3项有2项并排除反应性浆细胞增多及未明
原因良性丙种球蛋白增多症（免疫球蛋白
<35g/L）
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• differential diagnosis
1、reactive plasmacytosis：
2、MGUS、lyphoma、leukemia、
3、cancer of bone
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treatments
1、autologous SCT
对小于70岁的患者应
考虑自体干细胞移植术的
可能性。约50%的患者在
技术上可实施该项技术，
其疗效显著优于化疗，中
位生存时间42月。
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治疗
2、allo-geniec sct：
90%以上的患者
不适合。CR与死
亡率均为40%。
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treatment
3、化学治疗：
MP mephalan 8~10mg/d ×7day,
prednisone 60mg/d ×7day,
3~4 cyc
VAD 地塞米松40mg/d day 1~4,9~12,17~20
adiamycin day 1~4
长春新碱 day 1~4
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治疗
4、thalidomide：一种新生血管生长抑制剂，
对部分难治MM有效。
5、velcad：bortezomib
6 lenalidomide
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Gastritis
Xinjing Han
Department of Internal Medicine

The Second Affiliated Hospital of Chongqing Medical Univesity
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Introduction
 The epithelial reaction of stomach to
such a damage factor generally
include：
epithelial damage
inflammation
regeneration
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Introduction
 Gastropathy is reserved for mucosal

alterations (epithelial damage and
regeneration without inflammation) resulting
from chemical injuries or vascular
disturbances
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Introduction
 Gastritis is defined as inflammation of

the gastric mucosa (generally
accompanied with epithelial damage
and regeneration), regardless of its
etiology
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Introduction
In clinic practice
 we used to classify those which belong
to Gastropathy into Gastritis
 Gastritis is simply classified into
Acute Gastritis and Chronic Gastritis

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Acute Gastritis
 Acute Gastritis is defined as acute gastric
mucosa inflammation resulting from various
damage factors
 Gastric mucosal congestion, edema,
hemorrhage and erosion (superficial ulcers)
can be verified by endoscopy
 Lamina propria mucosae infiltrated by
Inflammatory cells (mainly neutrophils) is a
histopathologic feature
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The three subtypes of

acute gastritis
Acute helicobacter pylori gastritis
Acute gastritis infected with other pathogens
Acute erosive-hemorrhagic gastritis

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Acute helicobacter pylori gastritis
 diffuse gastritis associated with epigastric

pain, nausea, and vomiting, last for few days
or a week.
 diagnosed by a positive urea breath test
(UBT)or by the combination of positive
histology and negative serology for anti–H.
pylori IgG (proof for acute infection)
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Acute gastritis infected with

other pathogens
 Mucosa damage result from pathogenic

organisms infection and/or their toxin
 The infection rarely happens except those

patients who suffer from severe
immunodeficiency.
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Acute erosive-hemorrhagic
gastritis
 Characterised by multiple mucosal
erosion, hemorrhage and transient
superficial ulceration
Common damage factor include：
⑴ Chemicals: Alcohol, Drugs
⑵ Stress
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Directly
Epithelial
damage
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Directly
epithelial
damage
Repression
of
Cyclooxygenase, Weakend
Prostaglandin epithelial
decrease regeneration
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Drugs
non-steroidal anti-inflammatory drugs(NSAIDs):

indomethacin, aspirin
some chemotherapeutics : fluorouracil
Potassium chloride
Iron supplements
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⑵stress:
Severe trauma
Operation
A large area of burn
Cerebral vascular accident
Sepsis
Shock
MODS
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Severe burn Curling ulcer
CNS lesion Cushing ulcer

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stress Activity of platelet

activating factor
Mucosal ischemia
vasoconstriction
Mucosal hypoxia Mucous secretion↓ prostaglandin

↓
Mucosal barrier is damaged H+ back diffusion
Damage vessel Damage mucosa
bleeding erosion
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 Nausea, vomit, epigastric pain or

discomfort, melena, hematemesis,
early saturation, fullness sensation
 Active bowel sound
 Stool occult blood positive
 Positive findings by endoscopy within
24-48 hours
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chronic gastritis
 Defined as chronic inflammation of
gastric mucosa
 Mucosal infiltration of lymphocytes and

plasmocytes is a histopathologic
feature
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Updated Sydney System
non-atrophic(superficial)
Chronic multifocal atrophic (B)

Gastritis atrophic
autoimmune (A)
special forms
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HELICOBACTER PYLORI–
INDUCED GASTRITIS
 Helicobacter pylori -gram-negative microaerophilic

organism
 H.pylori is a gram-negative spiral bacterium
1.5 to 3.5um in size
 Its appearance is characterized by its helical shape
as well as by six sheathed unipolar flagella that
provide motility
 The organism produces urease,which appears to
be important in colonization of the gastric mucosa
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Epidemiology of of H.pylori infection

 H.pylori gastritis is one of the most common
human infection,with over 2 billionpeople
infected worldwide
 Transmission is opportunistic in that any
method that allows the organism access to
the stomach
 Bad household hygiene, contact of
contaminated food or water, gastric juice of
infected individuals (nasogastric tubes or
endoscopes)
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 In developing countries with low standards of
hygiene,the prevalence of H.pylori infection
increases dramaticallyin early childhood.In certain
countries,up to 90% of the population is infected by
age 10(China adult about 50%-70%).Spontaneous
clearance of the organism is extremely
uncommon,resulting in chronic life-long infection in
untreated persons
 In developed countries such as the United
States,the prevalence of H.pylori infection is
lower,with approximately 30% of the adult
population infected
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 Menbers of large families tend to have

a higher prevalence of infection.
 The majority of infections are probably

acquired in childhood
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pathophysiology of H.pylori infection
 H.pylori infection can be divided into an

early stage,characterized by colonization of
the host stomach,and a late stage,
characterized by clinical disease.
 Urease may be important in early
colonization by creatin a protective
nonacidic microenvironment shielding the
organism from gastric juice.
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 Motility is another important colonization factor

 Adherence to the gastric epithelial layer is another
essential factor enabling H.pylori to colonize the
human stomach,because without this
ability,organisms would be washed out with normal
gastric emptying
 Virulence factors associated with H.pylori infection
can be divided into those that lead to gastritis
(occurring in all infected persons)and those that
lead to additional clinical disease entities(occurring
only in some persons).
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 Urease and various other enzyme products of

H.pylori organisms are important in undermining
mucosal integrity,thereby leading to gastritis
 The Vac A gene,which encodes for a toxin that causes

vacuolization of infected culture cells,is present in all
H.pylori isolates,but only 50% of then express the
toxin.Vac A cytotoxin has been associated with the
development of peptic ulcer disease
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 Cag A is also a marker for

pathogenicity.The precise function of
the Cag A protein has not yet been
elucidated,but expression of Cag A is
associated with peptic ulcer disease as
well as gastric cancer and lymphoma.
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Effects of H.pylori gastritis on normal gastric physiology
H.pylori colonization
Acute H.pylori infection Epidemic achlorhydria
weeks to months
Chronic superficial gastritis

?
Antral predominant infection Corpus predominant infection
( acid output) ( acid output)
Duodenal Nonulcer Asymptomatic Gastric Chronic atrophic

ulcer dyspepsia Chronic ulcer gastritis
infection
Gastric Gastric
maltoma Antral
cancer
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Clinical Finding
Symptoms and signs:
Anorexia
Epigastric pain
Nausea
Vomitting
Hematemesis
“Coffee grouds”emesis
There is poor correlation between symptoms and the number
or severity of endoscopic abnormalities
The physical examination is nonspecific finding
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Erosive Nonerosive
gastritis gastritis
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Diagnosis
H. pylori test
 “noninvasive” modalities
· Serology: Anti-Hp IgG antibodies
· Carbon 13 or 14 urea breath test (UBT)
· Stool antigen test
 “invasive(endoscopic) ”
· Rapid urease test (RUT)
· Histology
· Culture
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Diagnosis of H.pylori gastritis

The diagnosis of H.pylori gastritis may be made using either invasive or
noninvasive methods
Diagnostic Tests For H.pylori Infection※
Test Sensitivity(%) Specificity(%)
Invasive
Histology 95 <100 □
Culture -60 100
Biopsy urease Test 90-95 98-100
Noninvasive
Serology ＃ 95 95
Urea breath Test 95-98 95-98
Stool antigen 95 95
※ Published values in clinical trials may be somewhat higher than those

encountered in clinical practice
□ Limited by observer error and histologic stains used
＃ Not useful for post-therapy cure determination

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Treatment
Lifestyle modification
 Quit Smoking and alcohol
 Avoid spicy food when disease is

active
 Reduce Coffee, tea ,cola consumption
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Medical treatment
1.Antacid and cytoprotective drugs

Antacid compounds are based on
aluminium and magnesium hydroxide
Sucralfate 1~2 pills tid
Bismuth compounds
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2.Antisecreroty drugs
 PPIs-proton pump inhibitors
Omeprazole, pantoprazole, lansoprazole
 H2-receptor antagonists
Famotidine, cimetidine
 Prostaglandin analogues
misoprostol
 Muscarinic(M1) receptor inhibitors
atropine
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3.Prokinetic agents :
Metoclopramide,
Domperidone ,
Cisapride ,
Mosapride
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4.Anti Hp therapy
 Triple-therapy
PPIs+metronidazole/tinidazole+clarithromycin
PPIs+amoxicillin+clarithromycin
PPIs+amoxicillin+metronidazole
(other antibiotics:tetrocycile, gentamycin,Furazolidone)
 Quadruple-therapy
Triple-therapy +bismuth(colloidal bismuth subcitrate)
7-14 days
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Inflammatory Bowel Disease

(IBD)
Xinjing Han
Department of Gastroenterology and Hepatology

The Second Affiliated Hospital
Chongqing Medical University
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Introduction
ntroduction
 Definition
□ Generalized :Inflammatory diseases
of GI tract.( infectious /non-infectious )
□ Narrow sense :Idiopathic inflammatory
bowel disease.(unknown causes)
- Tow main types: Ulcerative colitis,UC
Crohn’s disease,CD
- 5-15% IBD showing characteristics of both, called
indeterminate colitis.
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 In absence of established etiological
agents .
 Potential etiological agents
■ Environmental factors
■Genetics
■ Immunological factors
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 Environmental factors :
-diet
-smoking (bad for CD/good for UC)
-Mental factor : nervous,tired,
mentaldepression,
anxious , etc
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Potential etiological agents

■ Genetics
△ Positive family history for IBD
▲Most firmly established and quantitatively greatest
risk factor
▲ First-degree relatives: 15-8.9% for offspring;
8.8% for siblings; 3.5% for parents
△ Genetic influences overlaped

△ Multigenic
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Potential etiological agents

■Immunological factors
△ Evidence for activating immune response in
IBD
▲ Lamina propria infiltrated with lymphocytes,
macrophages, other immune cells
▲ Up-regulated immune genes in mucosa
▲ Specific antigen triggers for immune
response
PDFelement
△ Three hypotheses for antigenic triggers
▲ Microbial pathogens
▲ Dietary antigen or nonpathogenic microbial
agent
▲ Autoimmunity (autoimmune antigen on GI
cells)
PDFelement
△ Immunological events associated with inflammation
response in IBD
▲ Exogenous sensitization to lumenal antigen
▲ Antigen presentation by macrophage or dendritic cell
▲ Two groups of CD4+T cells involved: regulatory and
activated
▲ Activated macrophages and activated CD4+T cells
▲ Inflammatory cytokines; reactive oxygen species
produced by activated neutrophil
▲ Epithelial injury, vasodilation, enhanced permeability
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The normal gut wall is in a state of controlled inflammation. Increased

permeability of the intestinal wall allows access of luminal dietary and
bacterial antigens to immune effector cells...
PDFelement
Within gut wall, luminal antigens activate mononuclear cells and stimulate
the activated cells to produce proinflammatory cytokines, and histamine, and
perpetuating the inflammatory process...
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Ulcerative colitis
 Definition: Ulcerative colitis is a chronic
idiopathic inflammation limited to the rectum
and colon, up to now the disease’s origin has
not been cleared.
 Histological: Inflammation confined to
mucosa and submucosa, nongranulomatous.
 Distribution: Confined in
colon(sigmoid),sometimes involve rectum,
terminal ileum, continuous.
 Clinical characters: diarrhea,
mucopurulent bloodystool ,abdominal pain.
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Epidemiology
 Incidence and prevalence:
 Prevalence: all suffered
 Incidence: new suffered
 UC: incidence 2-10 /100,000; prevalence
35-100 /100,000; Europe and North
America
 Vary greatly with geographic location
 High in developed countries
 Uncommon in Asia but increasing
PDFelement
 Age
 Peak age: 20-40 yrs old
 Can occur in childhood or old age
 Gender
 Most show equal in males and females
PDFelement
Pathology
 General characteristics
 Diffuse, continuous
 Superficial mucosal or submucosal inflammation
 Large bowel
 Can begins in the rectum and extends to any
contiguous colon
 small intestine is seldom involved(terminal ileum)
 Macroscopic test :mucosal congestion, edema,

erosion,ulcer.
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 Microscopic test
■ Gland body is out of shape, disorganized,
decreased (atrophy)
■ Goblet cell ↓, Paneth cell metaplasia
■ Inflammatory polyp
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UC-Clinical manifestations
 Typically insidious rather than abrupt

 Chronic, recurrent
 Causes/aggravating factors:
diet,tired, mental, infection
PDFelement
Manifestations of digestive system
 Diarrhea:
■ mucopurulent bloodystool
■ Increased or decreased stool frequency
 Abdominal pain
■mild,moderate
■ left lower abdomen , lower abdomen , the
whole abdomen
■ paroxysmal;
persistent, drastic →toxic megacolon?

■ pain---diarrhea---anesis
■ tenesmus
PDFelement
 Others
■ abdominal distension
■ severe cases: anorexia,nausea,vomit
 Signs
■ tenderness in the left lower andomen
■ obvious tenderness, intestinal pattern
■ muscle guarding,rebound terderness,bowel
sound↓(toxic megacolon?perforation?)
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Extraintestinal manifestations
 Arthritis
 Osteoporosis
 Renal complications
 Dermatological manifestations
 Eye complications
 Thromboembolic complications
 Hepatobiliary compications
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PDFelement
Systemic symptoms
 Severe and fulminant UC
 Accompanied by diarrhea
 Fever
 Weight loss
 Weak
 Anemia
 Hypoproteinemia
 Electrolyte disturbance
 Nausea and vomiting
 Night sweats
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Classification
 Clinical types
 Symptomatic criteria for severity
of UC
 Activity
 Distribution
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Classification
 Clinical types:
 Initial onset
 Chronic recurrent: most common
 Chronic persistent
 Acute fulminant: seldom,severe,
complications
 Above types can transform to each other
PDFelement
Classification
 Symptomatic criteria for severity of UC

◆ Mild
◆ Moderate
◆ Severe
◆ Fulminant
PDFelement
Classification
 Symptomatic criteria for severity of UC
◆Mild
 <4 bowel movements per day
 No fever,tachycardia
 ESR (Erythrocyte sedimentation rate ):normal
 Bloodystool,anemia: no or mild
 Able to proceed with daily-life activities
PDFelement
□ Symptomatic criteria for severity of UC

◆Moderate
 4-6 stools per day
 Severity between the mild and severe
PDFelement
◆ Severe
■ >6 stools daily
■ Obvious mucopurulent bloodystool
■ T>37.5℃,persist for 2 days at least;
pulse>90bpm
■ HB<100g/L ,ESR>30mm/h
PDFelement
◆ Fulminant
 >10 stools daily
 Severe pain
 Relentless tenesmus
 Rebound tenderness
 Distention with tympanic bowel sounds
 Prostration, high fever, hypotension
 Radiography: Mucosal edema, Intramural air,
Colonic dilation
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PDFelement
Classification
 Activity
◆ Period of onset (active)
◆ In remission(quiescent)
PDFelement
Classification
 Distribution
■Proctitis (Rectitis )
■Proctosigmoiditis or Left-sided colitis
■Pancolitis or extensive colitis
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Ulcerative proctitis
 Limited to distal 15-20cm of rectum
 The most common and mildest UC
 25-30% of cases
 Typical presentation
 Hematochezia
 Constipated bowel movements
 Systemic symptoms uncommon
 Extraintestinal symptoms can occur
 Prognosis
 Usually remains confined to rectum
 Advance in 30-40%
PDFelement
Proctosigmoiditis or left-sided colitis
 40% of UC cases
 Intermediate syndrome presentation
 Either constipation or diarrhea
 Accompanied by tenesmus, bleeding
 Colicky left lower quadrant pain is more
common than proctitis
 Extraintestinal symptom is also common
 Prognosis
 The proximal margin usually fixed
PDFelement
Extensive colitis (pancolitis)
 Diagnosed when extends to transverse or

right colon
 Presentation
 More likely presenting with diarrhea
 Diminished absorptive capacity of colon
 Accompanied by rectal bleeding, tenesmus
 Diffused or localized cramping abdominal pain
 More likely having weight loss, systemic or
extraintestinal symptoms, anemia
PDFelement
Complications
 Toxic megacolon
■ Most severe manifestation of UC,5% of the severe
■ Diagnosed when inflammation extends from superficial
mucosa into submucosa and muscular layers

■ More common in extensive colitis but also in severe distal
colitis
■ Manifestation:Fever, prostration, severe cramps,
abdominal distention and tenderness ,etc.

■ Prognosis:bad, perforation.
PDFelement
Complications
 Canceration
■ rectum ,colon
■ pancolitis
■ juvenile-onset, chronic
PDFelement
Complications
 Others:
Bleeding :3%
Perforation
Intestinal obstruction:seldom
PDFelement
UC-Diagnosis
 History and physical examination
 Laboratory investigations
 Endoscopy
 Histology
 Imaging studies
PDFelement
Laboratory investigations
 Blood test
 Leucocytosis (WBC ↑)
 Anemia (RBC ↓)
 ESR elevation
 Hypoalbuminemia
 Electrolyte imbalance
 Fecal markers
 Fecal leukocytes-inflammatory diarrhea
mucus , pus ,blood;RBC, pyocyte , macrophage
 Exclude infectious diarrhea
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Endoscopy
 Establish the diagnosis
 Appearance
 Diffuse, continuous inflammation
 Beginning in rectum, extending to different
proximal locations
 Healthy colonic mucosa
 Smooth and glistening
 Inflammatory mucosa
 Edematous, erythematosus, more granular,
breaking apart the light reflection
 Mucosal granularity may be fine or coarse
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Histology
 Histological features parallel the
endoscopic appearance
 Principle components
 Disruption of glandular architecture
 Inflammatory infiltrate
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Imaging studies
 Conventional barium radiography
 Largely been supplanted by endoscopy
 Valuable in specific clinical situations
 Plain abdominal radiograph
 Severe UC
 Air-filled colon
 Extralumenal gas under diaphragm
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haustra of colon disappear, lead-pipe colon,mucosal granular,

round or oval filling defect ,small niche.
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 Chronic bacillary dysentery:
dysentery bacillus (feces,culture)
 Amoebiasis: entamoeba histolytica trophozoite
 Schistosomiasis :contact history ,
schistosomeovum
 Crohn’s disease (introduce later)
 Colorectal cancer: digital examination of the rectum
endoscopy,biopsy
 Irritable bowel syndrome: no pus or blood, no
disorder of organs,
 Others:pathogens,causes.
PDFelement
Treatment
 General measures
 Drugs
 Surgical
 Medical management of UC
PDFelement
General measures
 Rest
 Diet, Fasting
 Nutrition
 Total parenteral nutrition,TPN
 Correct electrolyte disturbance
 Transfusion
 Transfuse albumin
 Antibiotics: infection
PDFelement
Drugs
 Sulfasalazine(SASP)
 Mesalamine
 Corticosteroids
 Immunomodulators
PDFelement
■ Consist of 5-ASA(active component) and
sulfapyridine (toxic effects are due to this
moiety)
colonic bacteria
■ SASP colon 5-ASA+ sulfapyridine
It is activated in the colon by colonic bacteria,
so it is ineffective for small bowel.
PDFelement
■ How it works in IBD is unknow(because

other NSAIDs do not work).
■ On the concept of providing
▲Antibacterial: sulfapyridine
▲Antiinflammatory: 5-aminosalicylic acid
(5-ASA)
PDFelement
 Mesalamine:
■ 5-aminosalicylic acid (5-ASA)
■ Like sulfasalazine but active in small bowel if
taken orally;active in colon if given by
Suppositories or enema.
■ Few side effects
Rare and idiosyncratic reactions
Two Potential: Worsening of colitis ,Hypersensitivity
PDFelement
☆Sulfasalazine and 5-ASA are

primary therapies for mild to
moderately active UC and
maintaining remission
PDFelement
 Corticosteroids
■ For acute cases,espacially for the severe and fulminant
■ For mild,moderate cases failed to the treatment of
sulfasalazine and 5-ASA .
■ May be given as enemas (decrease systemic absorption,
“Budesonide”) or orally.
PDFelement
■ Work better in UC than CD.

■ If unable to taper steroid, this is indication
for antimetabolite and/or infliximab
■ Monitor: bone mineral density, ophtho
exam, adrenal insuff, glucose intolerance.
PDFelement
■ Used in refractory cases.
■ Include:
▲Antimetabolites
 Azathioprine and 6-mercaptopurine
 methotrexate
▲Calcineurin inhibitors
 Cyclosporine and Tacrolimus
▲Anti-tumor factor agents
PDFelement
■ Azathioprine and 6-MP:

▲ Azathioprine is prodrug conversed to
6-mercaptopurine.
▲ Inhibits purine metabolism and DNA
synthesis and repair, inhibiting
cellular proliferation.
PDFelement
■ Cyclosporine and Tacrolimus :

▲ Inhibit calcineurin, required for activation of T
lymphocytes
▲ Cyclosporine
 Induction in UC
 Severe steroid-refractory UC
 Concomitant steroids used in severe UC
 Goal to bridge to AZA or 6-MP as maintenance tx
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Surgical
 Emergency operation’s indications:
-Acute massive bleeding
-Acute perforation
-Severe cases threaten the life,failed
to the drug treatment.
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Surgical
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Medical management of UC
 Medical therapeutic decisions made
based on
 The extent of colitis
 The severity of colitis
 Prior clinical course, previous response
to therapies, concomitant medical
conditions
 Treat symptoms alone or long-term
therapy still debated hotly
PDFelement
Ulcerative proctitis
 Limited to rectum, good response to topical
therapy
 Mesalamine suppositories be mainstay
 Induction
 Nightly dosing (may twice or more)
 Maintenance
 Alternative-daily or twice-a-week dosing
 Topical corticosteroids
 Also effective, sometimes less irritating
 Oral mesalamine
 Many patients or physicians prefer to use
 Not effective as topical agents
PDFelement
Ulcerative proctosigmoiditis
 Many principles of proctitis can be

applied
 Topical therapy being mainstay
 Mesalamine-based
 Corticosteroid-based
 Combination with oral agents
PDFelement
Pancolitis
 30% with extensive colitis
 Most likely to undergo surgery
 At a higher risk for colorectal cancer
 Medical therapies decrease the risk
 Mild desease
 Oral mesalamine agents
 First-line therapy
 Combined with topical agents often helpful
 Sulfasalazine used decreasingly because of high
rates of intolerance
 Standard daily dose 2-3g
 High daily dose 4-4.8g
PDFelement
 Moderate disease
 Some response to high-dose oral mesalamine
 Topical mesalamine and corticosteroid helpful
 Corticosteroid
 Fro ones failed to above therapy
 Prednisone
 Typically starting with 40-60mg daily
 When remission induced
 Slowly taper therapy
 Mesalamine oral or topical
 Purine anologues
 Repeatedly relapse on corticosteroid taper
 Purine analogue or infliximab
PDFelement
 Severe disease
 Immediate evaluation and treatment
 Avoid progression to fulminant or toxic state
 Full assessment
 Starts with intravenous corticosteroids
 Divided dose or continuous infusion
 Combination with other therapies helpfull
 Oral mesalamine
 Topical mesalamine or corticosteroids
 Nutritional assessment
 Surgical consultation
 Show no response to corticosteroids within 3days, hard
to avoiding surgery
 Trying addition of infliximab or iv cycloporine
PDFelement
 Fulminant colitis and toxic megacolon

 Surgical emergency
 Dilation of the colon on radiograph
 Signs of systemic compromise
 Fever
 Tachycardia
 Hypotension
 Broad-spectrum antibiotics
 Rescuscitation
 Supportive therapies
PDFelement
Maintenance of remission
 Agent used to induce remission is often the
one to initially try to maintain remission
 With exception of corticosteroid-containing
therapy
 Maintenance starts when steroids weaned off
 The rate of steroids weaning
 Oral mesalamine-based maintenance
 Start with inducing dose
 Then decrease
 Purine analogues maintenance
PDFelement
Road
map
for
UC
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Crohn’s disease
 Definition: A chronic granulomatous inflammation that
may affect any portion of the GI tract, up to now the disease’s
origin has not been cleared.
 Histological: Inflammation extends through intestinal

wall from mucosa to serosa, granulomatous.
 Distribution: Involving entire GI tract potentially

(terminal ileum, proximal colon), skip lesions.
 Clinical characters: abdominal pain, diarrhea,

abdominalmass , fistula , intestinal obstruction .
PDFelement
Epidemiology
 Incidence and prevalence:
CD: incidence 1-6/100,000; prevalence 10-
100/100,000; Europe and North America
 Vary greatly with geographic location

 High in developed countries
 Uncommon in Asia but increasing
PDFelement
 Age
 Peak age: 15-30
 Can occur in any age
 Gender
 Most show equal in males and females
PDFelement
Pathology
 Focal, asymmetric, transmural inflammation
of GI tract
 Patchier (focal, discontinuous)
 Any segment of GI tract (From mouth to anus)
 50% affect terminal ileum and proximal right
colon
 Transmural nature
 Complications of stenoses (strictures) and
fistulae
 Histological Noncaseating granulomas-hallmark
 But only 30%, not necessary for diagnosis
PDFelement
PDFelement
CD-Clinical manifestations
 Presentations determined by site, extent,
severity, complications of intestine and
extraintestinal disease.
 Usually chronic but can be acute
 Symptoms:
 Digestive system’s symptoms
 Systemic symptoms
 Extraintestinal presentations
PDFelement
Manifestations of digestive system
 Abdominal pain
■ most common symptom
■ right lower abdomen , Periumbilial pain
■ intermittent onset
■ after meal ↑,after defecation or pass gas ↓
■ spasm? stenosis? obstruction? perforation?
 Diarrhea:
■ intermittent→ chronic,persistent
■ pasty stool,seldom with mucus ,pus,or
blood
■
PDFelement
 Abdominalmass:
■ 10-20%
■ right lower abdomen , periumbilical

area
 Fistula:
■ internal fistula→ diarrhea↑, malnutrition↑
■ external fistula→discharge stool,gas
 Lesions around the anus: perianal abscess ,
anal fissure ,etc.
PDFelement
Perirectal abcesses and fistulae

PDFelement
Extraintestinal manifestations
 Arthritis
 Acropachy
 Joint erythema
 Canker sore
 Eye complications
 Thromboembolic complications
 Hepatobiliary compications
PDFelement
Systemic symptoms
 Any more and more obvious
 Fever
 Malnutrition
 Weight loss
 Anemia
 Hypoproteinemia
 Vitamin deficiency
 Developmental delay (preadolescence )
PDFelement
Complications
 Intestinal obstruction: most common
 Intra-abdominal abscess:less common
 Fistulae
 Malabsorption syndrome
 Acute perforation,massive bloodystool
 Canceration
 Toxic megacolon:seldom seen
 Cholelithiasis
 Lithangiuria
 Fatty liver
PDFelement
Obstruction
 Signs and symptoms
 Depend on location of blockage
 Pyloric obstruction
 Jejunal obstruction
 Small obstruction
 Colonic obstruction
 Treatment
 Kept Nil by mouth
 Intravenous hydration
 Nasogastric suctioning
 Medical therapy
 Surgery
PDFelement
Abscesses and fistulae

 1/3 CD having penetrative complications
 Abscesses
 20% CD patients
 Intraabdominal abscesses:
 Pain, fever, chills, rigors
 Abdominal-pelvic CT scan or ultrasound
 Drainage-surgical resection
 Fistulae
 20-40% patients
 Any portion of the bowel affected by CD
 Medical therapy
 Surgery
PDFelement
CD-Diagnosis
 History and physical examination
 Laboratory investigations
 Endoscopy
 Histology
 Imaging studies
PDFelement
Laboratory studies
 Blood test
 Anemia(RBC↓)
 Leukocytosis(WBC↑)
 Thrombocytosis(PLT↑)
 Elevated erythrocyte sedimentation rates(ESR↑)
 Elevated C-reactive protein(CRP↑)
 Electrolyte disturbances
 Hypoalbuminemia
 Stool examination
 Fecal leukocytes,OBT(+)
 Stool volume↑---- Malabsorption syndrome
 Fecal fat ↑---- Malabsorption syndrome
PDFelement
Endoscopy
 Endoscopy and radiography are
complementary in the CD diagnosis
 As the primary diagnosis tool
 With ability to visualize directly and obtain
biopsies
 Distinguishing features of CD
 Rectal sparing areas of active disease
interspersed with normal mucosa
 Sharp, punched-out ulcerations surrounded by
normal mucosa
 Cobblestoning or nodular mucosa intersected by
crossing linear ulcerations
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 Endoscopies
 Colonoscopy
 Wireless capsule endoscopy
 Upper GI endoscopy
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Histology
 Reflecting the gross pattern of focal and
asymmetric intestinal involvement
 Aphthous ulcer
 Minute erosions overlying lymphoid
aggregates
 Crypt abscesses
 Noncaseating granulomas
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Imaging studies
 Air-contrast radiography
 Mucosal detail, colonic distensibility, and
strictures
 CT scan
 Urgent conditions
 Extralumenal complications
 Abscess
 Obstruction
 CT enterography
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 Enterophthisis
 Malignant lymphoma of small intestine
 Acute appendicitis
 UC(ulcerative colitis)
 Others
PDFelement
Comparison: CD VS. UC
CD UC
Pus and blood stool seldom commom
Distribution Patchy,noncontino continous
us
Affect rectum seldom commom
Affect Terminal ileum commom seldom
Enteric cavity stenosis commom seldom
Fistula commom rarely seen
Endoscopic appearance Linear ulcer, cobblestone Small ulcer, congestion,
appearance edematous,granular
Histology Inflammation involves all Inflammation confined to

bowel wall layers, mucosa and submucosa,
granulomas crypt abscess
PDFelement
Treatment
 General measures
 Drugs
 Surgical
 Medical management of CD
PDFelement
General measures
 Rest
 Diet, Fasting
 Nutrition ★
 Correct electrolyte disturbance
 Transfusion
 Transfuse albumin
PDFelement
 Five factors leading to malnutrition in

CD
 Diminished oral intake
 Increase in caloric requirements
 Malabsorption of nutients
 Loss of proteins and electrolytes in GI
lumen
 Drug therapy
PDFelement
 For most CD-adequate well-balanced diet

 Limited diet for some CD
 Some foods be eliminate
 consistently, reproducibly cause symptoms
 Lactose intolerance
 Avoiding lactase-containing food
 With strictures
 Avoiding fibrous, high-residue foods
PDFelement
 More CD nutritional therapy

 Treating nutritional deficiencies
 Supplementing specific nutients
 Iron, calcium, magnesium, zinc
 Multivitamin
 Fatty acid
 Defined formula diets
 Anorexia patients
 Oral or enteral therapy
 Parenteral nutrition
 Obstruction
 Massive intestine resection
PDFelement
Drugs
 Mesalamine
 Corticosteroids
 Antibiotics
PDFelement
■ Used in refractory cases,especially in CD on
chronic steroids.
■ Methotrexate
■ Cyclosporine and Tacrolimus
■ Infliximab (Remicade)(antibody to TNF-α ) is
used in severe CD.
PDFelement
Methotrexate
 Competitive inhibitor of dihydrofolate reductase
 Preventing DNA synthesis and purine production
 Decrease levels of many proinflammatory cytokines
 Methotrexate:
 IV MTX for induction in active CD or maintenance of
remission in inactive CD
 Induction steroid withdrawal in active CD
 Weekly IM MTX is effective for chronic active CD
 Insufficient evidence for induction or maintenance in
UC
 Monitor: CBC, LFT（Liver Function Test）
PDFelement
Cyclosporine and Tacrolimus
 Both bind specific proteins

 Inhibit calcineurin, required for activation of
T lymphocytes
 Cyclosporine
 Efficacy for CD w/ high doses (toxicity)
 Fistulizing CD w/ IV cyclosporine
 use in luminal CD
 Fistulizing CD with bridge to AZA or 6-MP
PDFelement
Anti-tumor factor agents
 Anti-TNF therapy is an exiting new pathway

 Most of them still under investigation
 Commercially available
 Infliximab
 Adalimumab
 Side effects
 Rare opportunistic infection
 Not be used in known or suspected infections,
neoplasm, demyelinating disease, or moderate
to severe heart failure
PDFelement
 Infliximab (TNF-α antibody)

 CD with inadequate response to conventional tx
 If used for induction, continue w/ maintenance
 Fistulizing CD
 UC patients without adequate response to
conventional tx
 Withdraw or taper concomitant steroids
 Avoid: active infection, demyelinating d/o, CHF,
malignancy, screen for TB
PDFelement
 Antibiotics
■ Metronidazole has been used to induce
disease remission with some success.
■ Fistulizing CD
■ Postop recurrence
■ No evidence in UC
■ Pouchitis
■ Infectious complications
PDFelement
Surgical indication
 Complete intestinal obstruction
 Fistula
 Abscess
 Acute perforation
 Massive bleeding uncontrolled
PDFelement
Medical management of CD
 Most recommendations in UC are
carried over to CD
 Location and severity of CD guide
therapeutic management
 Lumenal disease
 Fistulous disease
 Two stages of therapy
 Induction
 Maintenance
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Mild to moderate CD
 First-line therapy
 Mesalamine agents
 Antibiotics
 Failed to first-line thrapy
 Budesonide
 Azathioprine
 Methotrexate
PDFelement
Moderate to severe disease
 Steroids
 Budesonide
 Prenisone
 Anti-TNF
 Infliximab
 Adalimumab
PDFelement
Fistulous CD
 Combined medical and surgical

approach
 Antibiotics
 Drainage
 Azathioprine
 Methotrexate
 Infliximab
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Road map for CD

PDFelement
Gastrointestinal Bleeding
Xinjing Han

PDFelement
Introduction
 Definition
 Any bleeding that starts in the gastrointestinal tract,
which extends from the mouth to the anus.
 Bleeding amount:
 Microscopic bleeding (occult): only detected by
laboratory testing
 Overt bleeding: feces or vomit appearing special
blood-related color
 Massive bleeding: pure blood, acute, massive, and
life threatening
 Manifestations depend on the location and rate of
bleeding
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 Bleeding sources:
 Any site along the GI tract
 Two parts divided by Treitz ligament
 Upper GI bleeding
 Between the mouth and the upper part of the
small intestine
 Lower GI bleeding
 Between the upper part of the small intestine
and the anus, includes the small and large
bowels
 The bleeding manners are different
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Jejunum
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GI bleeding significance
 May point to many significant diseases and
conditions
 Prolonged microscopic bleeding
 leading to loss of iron, causing anemia
 Acute, severe, massive bleeding
 leading to hypovolemia, shock, and even death
 For patients with liver cirrhosis
 precipitating hepatic encephalopathy or hepatorenal
syndrome
 For patients with underlying ischemic heart
disease
 developing angina because of hypoperfusion
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Epidemiology
 Overall prevalence of GI bleeding
 very common clinical problem
 Over 300,000 hospitalizations annually in US
 Resulting in significant morbidity, mortality, and cost
 Overall incidence of Upper GI bleeding
 100/100,000, 76% of all GI bleeding
 Most common cause:
 Peptic Ulcer: 50-75%
 Predominance not affected by antisecretory drugs use
 Followed causes:
 Variceal bleeding, acute erosive and hemorrhagic
gastritis, and gastric cancer are followed
 Elderly patients accounting for 35-45% and increasing
steadily
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 Overall incidence of Lower GI bleeding

 Far less common, 20-27/100,000, 24% of all GI
bleeding
 Most common causes:
 Hemorrhoids
 Diverticulosis: 42-55% of lower GI bleeding
 Angiodysplasia: 30% of lower GI bleeding
 Neoplasia: colorectal neoplasia
 Less common causes:
 Colonic ischemia
 Inflammatory bowel diseases
 Infectious causes etc.
 Higher in men than women, for unknown reason
 The elderly are at increasing risk
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 Overall mortality of GI bleeding

 Overall mortality rate 5-12%
 Mortality from upper GI bleeding remained stable at 10%
 Mortality from lower GI bleeding decreased dramatically,
now below 5%
 Obscure Gastrointestinal Bleeding (OGiB)
 Bleeding from the GI tract that persists or recurs without
an obvious etiology after standard bidirectional endoscopy
and radiological evaluations
 5-10% of all cases of GI bleeding
 Among OGiB, 27-40% have lesions in small bowel
 The most common cause is vascular lesions, 70-80%
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Etiology
 Bleeding Location
 Upper GI (above the ligament of Treitz)
 Lower GI (below the ligament of Treitz)

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Common Causes of GI Bleeding

Upper GI tract
Duodenal ulcer (20–30%)
Gastric or duodenal erosions (20–30%)
Varices (15–20%)
Gastric ulcer (10–20%)
Mallory-Weiss tear (5–10%)
Erosive esophagitis (5–10%)
Angioma (5–10%)
Arteriovenous malformation (< 5%)
Gastrointestinal stromal tumors
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Lower GI tract (percentages vary with the age group
sampled)
Anal fissures
Angiodysplasia (vascular ectasia)
Colitis: radiation, ischemic, infectious
Colonic carcinoma
Colonic polyps
Diverticular disease
Inflammatory bowel disease: ulcerative proctitis/colitis,
Crohn's disease
Internal hemorrhoids
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Special:small bowel bleeding

Small-bowel lesions (rare)
Angiomas
Arteriovenous malformations
Meckel's diverticulum
Tumors
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1.Nonvariceal esophageal bleeding

 Esophagus is an important site of GI bleeding
 Typically presents with hematemesis or melena
 A careful history is essential in assembling an
accurate differential diagnosis
 Esophageal mucosa normally devoid of large
vessels
 In absence of varices or bleeding diathesis, acute
esophageal bleeding is caused by deep injury to the
esophagus or abnormally superficial arterial
branches
 Numerous causes of esophageal bleeding:
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Mallory-Weiss tear
 Mucosal laceration of
the gastric cardia or
gastroesophageal
junction
 First described in 1929
by Kenneth Mallory and
Soma Weiss
 Account for 5% to 15%
of upper GI bleeding
 Common in alcoholics
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Mallory-Weiss tear
 Classic presentation
 Repeated retching, vomiting or coughing
before hematemesis
 50% not give a history of antecedent
retching or vomiting
 Blood loss usually modest and 10% with
hemodynamic compromise
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Mallory-Weiss tear
 Typical endoscopic appearance
 A mucosal tear in the cardia
 Just below the gastroesophageal junction
 bridging the GE junction
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Reflux esophagitis
 GERD is a very common disorder

 causing monthly symptoms in up to 36% of
the U.S. population
 Reflux esophagitis
 Occurs in a subset of GERD
 Esophageal inflammation is visible as erosions
or ulcerations
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Linear ulcers (arrows) in the distal esophagus of a

patient with erosive esophagitis
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2.Peptic ulcer disease

 The most common cause of upper GI bleeding:
over 50% of all upper GI bleeding cases
 The number of hospitalizations for hemorrhage
associated with ulcers has remained unchanged
 Ulcer bleeding stops spontaneously in at least
80% of patients
 The overall mortality is also unchanged over the
last 30 years, ranging from 6 to 7% in the United
States
 Without specific hemostatic intervention, peptic
ulcer bleeding continues or recurs in
approximately 20% of patients
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Gastric ulcer bleeding

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3. Acute Gastropathy (acute mucosal lesions)

 Hemorrhagic gastric erosions
 lesions can be diffuse
 typically involve the gastric body and fundus
 bleeding can be massive
 Causes:
 NSAIDs, alcohol, stress
 Pathogenesis:
 imbalance between aggressive and protective mucosal
factors
 Diagnosis:
 readily made on endoscopy
 Treatment:
 Increase gastric pH
 H2RAs or PPIs
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Acute Gastropathy
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4.Portal Hypertensive GI Bleeding
 GI hemorrhage from portal hypertension

 Highest mortality, 30-40%
 High rate of recurrence
 Consequences of portal hypertension
 Vascular collaterals formation (varices)
 In stomach, esophagus, small bowel, and colon
 High risk of rupture and bleeding
 Vascular congestion
 Portal hypertensive gastropathy, enteropathy,and
colopathy
 Leading to mucosal bleeding
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Esophageal and gastric varices
 Development of varices in cirrhosis

 In 60% decompensated cirrhosis
 In 30% compensated cirrhosis
 Incidence of variceal bleeding in
cirrhosis
 Known esophageal varices is 10-15%
per year
 Large varices is 20-30%
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Esophageal varices Gastric varices

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Bleeding esophageal varix (arrow)

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Portal hypertensive gastropathy
 Mechanism:
 Increased mucosal blood flow and passive
congestion of the submucosa
 Gastropathy
 accounts for 8% to 20% of acute bleeding in
patients with portal hypertension
 can also lead to chronic blood loss
 Many patients presenting with bleeding from
portal hypertensive gastropathy have recurrent
bleeding
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Portal hypertensive gastropathy

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5. Obscure upper GI bleeding
 Prevalence:
 5% in patients with upper GI bleeding
 Two clinical forms:
 obscure-overt
 with recurrent passage of visible blood
 obscure-occult
 as manifested by recurrent IDA and/or
recurrent positive FOBT results.
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Obscure upper GI bleeding
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Gastric Antral Vascular Ectasia(GAVE)
 Increasingly recognized as cause of occult

bleeding
 Most common in elderly women
 Generally experience occult bleeding and anemia
 Higher frequency with autoimmune disorders and
atrophic gastritis, hypergastrinemia, cirrhosis, or
portal hypertension
 Typical endoscopic appearance:
 resembles stripes on a watermelon
 rugal folds containing a column of vessels that
converge at the pylorus.
 Treatment:
 has not yet been established
 Supportive treatments with blood transfusions,
steroid use, endoscopic ablation, or surgical
treatments
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Gastric antral vascular ectasias are large, dilated

veins running linearly along the stomach in a
pattern resembling a watermelon.
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Dieulafoy’s Lesion
 A large artery very close to the mucosal surface

 Possibly as a congenital lesion.
 Traditionally refers to lesion in proximal stomach
 1/3 lesions found elsewhere in GI tract
 most in duodenum, also in esophagus, jejunum,
and colon
 Bleeding is frequently life threatening
 Bleeding mechanisms
 Not well characterized
 Spontaneous thrombosis and perforation
 An abnormally large (1–3mm), tortuous,
submucosal artery
 Through the center of a solitary 2–5mm gastric
mucosal defect.
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Dieulafoy's lesion is a large artery that penetrates

the gastric wall
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 Presentation:
 Hematemesis, usually
 Hematochezia, 1/3
 Diagnosis:
 37% of patients, more than one
endoscopic procedure
 Endosonography is useful
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6. Lower GI bleeding
 Bleeding from a site distal to Treitz
 Less common than upper GI bleeding
 More from colonic rather than small bowel
source
 The most common diagnoses
 Hemorrhoidal bleeding
 Diverticular
 Vascular anomalies
 Colorectal cancer
 Infectious or inflammatory colitis
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Hemorrhoids
 The most common cause of lower GI

bleeding
 Hemorrhoidal bleeding manner
 Typically small volume and intermittent
 Bright red blood on surface of stool or paper
 Occasionally bleeding is severe
 Confirmed diagnosis
 Anoscopy
 Flexible sigmoidoscopy
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Colonic diverticulum
 The second most common cause

 Develop as a result of increased intraluminal
pressure and occur at sites of natural weakness
in the colonic wall where transmural arteries
are located.
 Manner
 brisk but usually self-limited bleeding
 Rarely massive
 Diagnosis is often made by finding diverticular
on colonoscopy
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Vascular anomalies
 Angiodysplasia
 Sporadic and secondary, are a common cause of
bleeding from the small bowel and colon
 Dieulafoy lesions
 rarely lead to bleeding from the small bowel and
colon
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Various appearances of colonic angiodysplasia

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Colorectal neoplasm
 Colorectal cancer
 most commonly with occult blood loss
 rectosigmoid lesions may with hematochezia
 Diagnosis
 digital examination of the rectum
 readily made on endoscopy.
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Colon Cancer
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Strategy for diagnosis and

management of GI bleeding
 Assessment of patient
 GI bleeding recognition(realy GI bleeding?)
 How much blood lost
 Bleeding ongoing or ceased?
 Resuscitation
 Dire consequences are shock.
 Determine the source of bleeding
 Brief history and physical examination
 Upper or lower GI tract
 Urgent vs elective endoscopy
 Urgent endoscopy proposed for all patients
 Empirical medical therapy before endoscopy
 Specific therapy
 When a definitive diagnosis made
 Medical, endoscopic, angiographic, or surgical
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Step 1: GI bleeding recognition
1. GI bleeding manifestations
2. Hypovolemia or shock
3. Anemia and blood abnormality
4. Fever
5. Azotemia
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1.Manner of GI bleeding presentation
 Hematemesis
 Vomiting of red blood
 Indicates upper GI bleeding
 Acute
 Coffee-ground vomitus
 vomiting of dark brown, granular material that like
coffee grounds
 From upper GI bleeding that has slowed or stopped
 Conversion of red Hb to brown hematin by gastric
acid
 Distinguish:Hemoptysis? Nosebleeding?
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 Hematochezia
 Bright red or maroon blood from the rectum
 pure blood
 blood intermixed with formed stool
 bloody diarrhea
 Usually indicates lower GI bleeding
 May result from vigorous upper GI bleeding
 rapid transit of blood through the intestines
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 Melena
 Shiny, black, sticky, tarry stool
 At least 50 to 100ml blood from upper GI tract
 Degradation of blood in intestine
 May persist for several days
 Typically indicates upper GI bleeding, may also

from small bowel or right colon
 Black stool with negative occult blood
 Exogenous stool darkeners mistaken for
melena
 Ingestion of iron, bismuth, or various foods
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 Chronic occult bleeding
 Occur from anywhere in the GI tract
 Detectable by testing stool sample with
McAb(monoclonal antibody) for human
hemoglobin
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2.Hypovolemia or shock
 Speed and volume of blood loss

 Symptoms
 Weakness
 Giddiness
 Oliguria
 Cold (feet,hands)
 Sweating
 Signs:
 Blood pressure↓
 Pulse↑
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 Vital signs:
 Postural hypotension
(orthostatic hypotension)
---- early physical finding
A postural drop in blood pressure of 10 to 15 mm Hg
 tachycardia
---- greater loss, compensate
 recumbent hypotension
---- final results
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3.Anemia and blood abnormality
 Syptoms
 Pale
 dizziness
 palpitation
 fatigability
 Dyspnea
 Blood abnormality
 RBC count, Hb (hemoglobin), Hct (hematocrit)
 Early stage of bleeding: may appear normal, not diluted
by tissue fluid
 Anemia occurs after 3-4 hrs, reaches peak at 24-72hrs
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4.Fever
 Acute massive GI bleeding

 Found within 24 hrs
 <38.5℃
℃
 Continuing for 3-5 days
 Mechanism
 Not clear
 Related to hypovolemia
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5.Azotemia
 blood urea nitrogen(BUN) ↑

 As a result of breakdown of blood proteins
by bacteria to urea and reuptake of this
from the gut
 Starting from several hours after bleeding
 Peaking at 24-48 hrs
 Normalizing after 3-4 days
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6.Misleading factors for GI bleeding
 Often misleading
 Bleeding outside GI tract: nasopharynx
 Food or drugs
 History and physical examination suggest a
diagnosis in about 50% of patients
 Confirmatory testing is required
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Step 2: Patient assessment
 Bleeding amount and speed evaluation

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Amount and speed evaluation

 postural hypotension
 10–20% volume loss
 Resting Hypotension and tachycardia
 30% loss of blood volume
 Syncope
 rapid blood loss of as little as 10% volume
 Hematochezia
 at least 1000 ml in the setting of upper GI hemorrhage
 Red hematemesis and concomitant hematochezia
 massive brisk bleeding in the UGI tract
 with a 30% mortality before and during diagnostic
evaluation
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Step 3: Resuscitation
 Several findings suggest hypovolemia or

hemorrhagic shock.
 Syncope
 Hypotension(BP↓)
 Pallor (face)
 Sweating
 Tachycardia(HR↑)
 Stabilization with airway management;
IV fluids, or blood transfusions is
essential
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Step 4: The source of bleeding
 Hematemesis/coffee-ground emesis
/melena
 more proximal to UGI
 Hematochezia
 more distal colorectal lesion
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Step 5: The causes of bleeding
Diagnostic approach to GI bleeding

1. History and physical examination
2. Endoscopy
3. Barium radiography
4. Angiography
5. Radionuclide scans
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1. History and physical examination

 50% of bleeding causes can be guessed after
careful history and physical examination
 History raises specific diagnostic possibilities
 Peptic ulcer or dyspepsia
 Liver cirrhosis
 Malignancy---Weight loss/change in bowel habit
 Mallory-Weiss---Vomiting/retching before hematemesis
 Physical examination provides diagnostic clues
 Stigmata of cirrhosis
 Hepatic or splenic enlargement
 Hereditary vascular anomalies
 Abdominal tenderness
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2. Endoscopy
 Diagnostic endoscopy
 Locate precisely site and stigmata of bleeding
 Safe and simple
 The timing of the diagnostic endoscopy:
 Depends on the severity and suspected
cause
 Urgent endoscopy(within 24-48 hr)
 fail to stop bleeding with simple supportive care
 underlying cirrhosis
 For most patients whose bleeding ceases
 can be postponed for 24 hr
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 Major endoscopy
 Upper GI endoscopy
 examination of the esophagus, stomach, and duodenum
 Colonoscopy
 colon
 Double-balloon enteroscopy
 Small intestine
 Capsule endoscopy
 Small intestine
 Intraoperative enteroscopy
 Small intestine
 Therapeutic potential
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Upper endoscopy is generally performed first, and if no

bleeding source is located, then lower endoscopy is performed
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Wireless Capsule endoscopy (WCE)
 Developed in the late 1990s

 Allowing imaging of entire small intestine
 The best way for seeing the small
intestinal mucosa
 Procedure:
 The capsule is ingested
 Images are downloaded as a video file
 be reviewed and interpreted at a
convenient time
 Absolute contraindications
 GI obstruction
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Intraoperative enteroscopy
 Gold standard of small bowel imaging

 High sensitivity:
 The yield of detecting bleeding lesions in the
small intestine reaches 83%–100%
 Last choice:
 At the cost of marked invasiveness
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3. Barium radiography
 Upper GI barium x-rays have no role in

acute bleeding
 Bleeding stopped for 3 days at least
 The contrast used may obscure subsequent
attempts at angiography
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4. Angiography
 Only if endoscopy has failed

 The bleeding must be arterial
 Achieve a rate of at least 0.5–1 ml/min
 Diagnose difficult cases of recurrent GI
bleeding from an unknown source.
 A therapeutic alternative
 Delivery of intraarterial vasopressin in stress
gastropathy
 Embolization of bleeding ulcers or neoplasms
in inoperable patients
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Positive mesenteric angiogram in patient with a

bleeding colonic diverticulum
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5. Radionuclide scans
 Reveal bleeding
 even when the rate of blood loss is as low as 0.5
ml/min
 Major disadvantage:
 localize the bleeding to an area of the abdomen
 do not diagnose the specific location or the
responsible lesion
 Often used in
 Determining which patients have sufficient
ongoing bleeding to warrant angiography
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A positive (arrows) tagged red blood cell scan in a

patient with bleeding from the sigmoid colon
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Treatment
1. Emergent and intensive care
 Secure airway if needed
 Fluid resuscitation
 Blood transfusion if needed
2. Specific hemostasia therapy
 Causes and hemostasis
 Four types of methods
 Medical
 Endoscopic
 Angiographic
 Surgical
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1. Emergent and intensive care
 Emergent situation:
 Hematemesis ,hematochezia, melena
 Syncope,hypotension(BP↓),pallor(face),s
weating,tachycardia(HR↑)
 Admission to ICU
 All patients with severe GI bleeding
 General treatment
 Fasting,bed rest,oxygen uptake
 Maintenance of airway
 Restoration of circulating volume
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Airway
 Aspiration of blood
 Major cause of morbidity and mortality
 Prevention
 Endotracheal intubation
 in patients who have inadequate gag
reflexes or are obtunded or unconscious
 Particularly undergoing upper endoscopy
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Fluid resuscitation
 For any patient with hypovolemia or hemorrhagic

shock
 Normal saline
 until signs of hypovolemia remit
 Transfusions
 type and cross,CBC
 Packed RBCs
 Until intravascular volume is restored
 In older patients or those with coronary artery disease
may be stopped when Hct is stable at 30
 Younger patients or those with chronic bleeding are
usually not transfused unless Hct is < 23
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2.Specific hemostasia therapy

 Some key points for hemostasis :
 GI bleeding stops spontaneously in 80% of
patients
 The remaining patients require some type of
intervention
 Specific therapy depends on the bleeding site.
 Early intervention to control bleeding is important
to minimize mortality, particularly in elderly
patients.
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 Three types of causes of bleeding

 Nonvaciceal upper GI bleeding
 Variceal bleeding
 Lower GI bleeding
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(1) Nonvariceal upper GI bleeding
 Main Causes:
 Peptic ulcer
 Gastric erosions or gastropathy
 NSAIDs, alcohol, portal, stress
 Other common causes:

 Mallory-Weiss tear
 Esophagitis and esophageal ulcers
 Erosive duodenitis
 Neoplasms
 Dieulafoy disease
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 Four types of methods

 Medical management
 Endoscopic methods
 Surgery
 Angiography
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A. Medical management
 PPIs
 Therapeutic goal
 Prevent clot dissolution
 Allow healing of underlying lesion
 How to achieve the goal

 Maintaining gastric pH above 6.0
 Favoring coagulation pathways
 Improving platelet adhesiveness
 High-dose PPIs
 Omeprazole or pantoprazole administration
 80mg bolus injection followed by 8mg/h
continuous infusion
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 Octreotide
 Analogue of somatostatin: inhibitory
neuropeptide
 Inhibits portal venous and arterial blood flow
to stomach and duodenum
 Reducing the risk of continued bleeding and
need for surgery
 Not recommended for routine treatment of
nonvariceal upper GI bleeding
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B. Endoscopic methods
 For patients with persistent or recurrent

hemorrhage
 Safer than emergency
 Divided into thermal and nonthermal types
 Injection sclerotherapy,titanclip
 Thermal methods
 Bipolar electrocoagulation
 Heater probes
 Laser
 Argon plasma coagulator (APC)
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C. Surgery
 When endoscopy and medical therapy fail

 Be used in patients with continued bleeding
 Localization of the bleeding site is very
important
 Blind hemicolectomy carries a much higher
mortality risk than does directed segmental
resection
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D. Angiographic hemostasis
 Methods above are ineffective or unfeasible

 Angiography with embolization
 requires significant expertise
 causes complications
 collateral blood flow to the bowel is limited
 risk of bowel ischemia or infarction, < 5%.
 Angiography with Vasopressin infusion
 80% success rate for stopping bleeding
 but bleeding recurs in about 50% of patients
 risk of hypertension and coronary ischemia
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(2) Variceal bleeding
 Most rapid type of upper GI hemorrhage

 Two types
 Esophageal varices
 Gastric varices
 Special management
 Medical therapy
 Endoscopic therapy
 Balloon tamponade
 TIPS
 Surgery
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 Urgent endoscopy
 For patient with suspected variceal bleeding
 Half to two-thirds of patients with cirrhosis
 Bleeding sources are nonvariceal
 Variceal bleeding treatment is different
from bleeding with other causes
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A. Medical therapy
 Extensively studied, the benefit remains

uncertain
 Vasopressin and analogues
 reduced early rebleeding rates
 But significant toxicity from systemic
vasoconstriction
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 Somatostatin and analogues (octreotide)

 Replacing vasopressin in treatment of variceal
hemorrhage
 Reducing portal pressure by decreasing
splanchnic blood flow
 Combination with endoscopic therapy
significantly lowers rebleeding rates
 Continuing for a duration of 5 days
 A loading dose of 50 mcg(microgram ) IV is
given, followed by an infusion of 25 mcg to 50
mcg per hour for a duration of 5 days.
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B. Endoscopic therapy
 The mainstay of therapy of esophageal variceal

bleeding
 Two types
 Endoscopic sclerotherapy of varices
 Endoscopic variceal band ligation
 Risk of rebleeding is significantly reduced
 50% with sclerotherapy and 35% with band ligation
 Band ligation has supplanted sclerotherapy
 Repeated sessions until varices are eradicated
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Bleeding esophageal
varix undergoing
sclerotherapy
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Endoscopic variceal band

ligation
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图例
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C. Balloon tamponade
 An important therapeutic tool

 Brisk variceal hemorrhage cannot be controlled on
initial endoscopy
 Gastric balloon should not remain inflated for
more than 48 hours at one time
 Esophageal balloon should be inflated
 only if bleeding continues despite inflation of the
gastric balloon
 for no more than 8 hours at a time due to the high
risk of tissue necrosis
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D. TIPS
 Transjugular intrahepatic portosystemic shunt

(TIPS)
 Portal decompression
 A bridge to liver transplantation
 An expandable metallic stent is placed between
the hepatic and portal veins within the liver by
means of an angiographically guided catheter
 10%–15% procedure complication rate and a 5%
incidence of hepatic encephalopathy
 In one-third of patients, TIPS stenosis or
occlusion develops by 1 year of follow-up
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E. Surgery
 Patients
 Continuing to bleed
 Having more than one rebleeding episode
 Child’s cirrhosis
 Shunting surgery
 Shunting portal blood to the systemic circulation
 portal decompression
 Several types
 End-to-side portacaval
 Side-to-side portacaval
 Mesocaval
 Splenorenal shunts
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 Esophageal transection with paraesophagogastric

devascularization
 Splenopneumopexy
 Hepatic transplantation
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Prevention of recurrent variceal bleeding
 Repeat outpatient endoscopic therapy

 Until varices are eradicated
 Endoscopy is repeated every 3 to 6 months in
order to monitor for recurrent varices
 Oral beta-blocker (βRB) therapy
 Used in combination with endoscopic therapy
 Non-selective beta-blockers are preferred
 splanchnic vasodilation and decreased cardiac
output
 The dose is titrated to reduce the resting pulse
by 25%
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(3) Lower GI bleeding

 Two major causes of acute bleeding
 Diverticulosis
 Angiodysplasia
 80% spontaneously stop
 Treatment
 Endoscopic treatment
 Angiographic intervention
 Urgent surgery
 Medical therapy
 Vasopressin and analogues
 somatostatin and analogues
 Thrombin clyster
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Etiology of UGI bleedings:Mallory’s

Vices Gave (her) An Ulcer.
 Mallory-Weiss tear
 Varices
 Gastritis/Gastric cancer
 Arteriovenous malformation
 Ulcer(peptic)
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Etiology of LGI bleedings: Can U Cure

Aunt Di’s Hemorrhoids?
 Cancer or polyps
 Upper GI bleeding(need to rule it out)
 Colitis
 Angiodysplasia
 Diverticulosis
 Hemorrhoids
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THANKS!
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BLEEDING DISORDERS
重庆医科大学第二医院血液内科
邓建川
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Petechiae &
Purpura
(typical of platelet disorders)
Do not blanch with

pressure
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Ecchymoses
(typical of coagulation factor
disorders)
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Normal hemostasis
Definition of hemostasis
• Haemostasis – capacity to minimise loss
of blood following injury to blood vessel.
• The arrest of bleeding by repair of vessel
wall
• Maintaining a balance
– Coagulation
– Fibrinolysis
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Haemostasis overview:
BV Injury
Contact/
Neural Tissue
Factor
Blood Vessel Platelet Coagulation

Constriction Aggregation Cascade
Primary hemostatic plug
Reduced Platelet
Activation Fibrin
Blood flow formation
Stable Hemostatic Plug

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Normal hemostasis
Systems Involved in hemostasis
• Vascular system
– Injured vessel initiates vasoconstriction
• Platelet System
– Injured vessel exposes collagen that initiates
platelet aggregation and help form plug
• Coagulation System
– protein factors of intrinsic and extrinsic
pathways produce a permanent fibrin plug
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Coagulation System
Secondary hemostasis
• Intrinsic Pathway
– All components required for initiating this
pathway are circulating in the blood
– triggered by contacting with collagen or glass
• Extrinsic Pathway
– Initiated by the release of tissue factor and
calcium from damaged tissue
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Coagulation factor
• Fibrinogen FI
• Prothrombin F II
• Tissue factor ( tissue thromboplastin) F III
• Ca2+ F IV
• Antihemophilic factor F VIII , coexisted with VWF
• F II , F VII , F IX , FX , vitamin K dependent
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Coagulation cascade
Intrinsic system (surface contact) Extrinsic system (tissue damage)
XII XIIa Tissue factor
XI XIa
IX IXa VIIa VII
VIII VIIIa
X Xa
Vitamin K dependant factors
V Va
II IIa (Thrombin)
Fibrinogen Fibrin
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Waterfall sequence
XII XIIa
for
Intrinsic Pathway
XI XIa
IX IXa
VIIIa+Ca+Pl
X Xa
Va+Ca+Pl
II IIa
Fibrinogen Fibrin
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Extrinsic Pathway
X Xa
Va+Ca+Pl
II IIa
TF / VIIa
Fibrinogen Fibrin
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Activation of the Common Pathway
INTRINSIC EXTRINSIC
Collagen Tissue Factor
XII
XI VII
IX
VIII
V FIBRINOGEN (I)
PROTHROMBIN THROMBIN
(II) (III) FIBRIN
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The Hemostatic Balance
Coagulation Fibrinolysis
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Clot inhibition/lysis
• Anticlotting mechanisms are activated to allow
clot disintegration and repair of the damaged
vessel
- Activated protein C
- Antithrombin III
- TFPI (Tissue factor pathway inhibitor )
- Fibrinolytic system
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Fibrinolytic system
• Definition: temporary fibrin clot systematically
and gradually dissolved as the vessel heals
• Key components
– Plasminogen (inactive form)
– Plasminogen activators
– Plasmin
– Fibrin
– Fibrin Degradation Products (FDP)
– Inhibitors of plasminogen activators and plasmin
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LABORATORY EVALUATION
Screen tests
• Platelet Count
• Bleeding Time (BT)
• Prothrombin Time (PT)
• Activated Patial Thromboplastin Time
(APTT)
• Thrombin Time (TT)
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Bleeding Time
Provides assessment of platelet count and

function
NORMAL VALUE
2-8 MINUTES
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Prothrombin Time
 Measures Effectiveness of the Extrinsic
Pathway
NORMAL VALUE
10--15 SECS
10
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Activated Partial Thromboplastin

Time
 Measures Effectiveness of the Intrinsic
Pathway
NORMAL VALUE
25--40 SECS
25
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Laboratory Evaluation of the

Coagulation Pathways
Partial thromboplastin time Prothrombin time
(APTT) (PT)
Surface activating agent Thromboplastin
(Ellagic acid, kaolin) Tissue factor
Phospholipid Phospholipid
Calcium Calcium
Intrinsic pathway Extrinsic pathway
Thrombin time
(TT) Common pathway
Thrombin
Fibrin clot
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o
Initial Evaluation of a Bleeding Patient -
1 b
Normal PT h
Abnormal APTT
n
Test for factor deficiency: s

Isolated deficiency in intrinsic pathway (factors VIII, e
IX, XI)
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Initial Evaluation of a Bleeding Patient -

2
Abnormal PT
Normal APTT
Test for factor deficiency:

Isolated deficiency of factor VII (rare)
Multiple factor deficiencies (II,VII,X, common)
(Liver disease, vitamin K deficiency, warfarin, DIC)
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Thrombin Time
 Time for
Fibrinogen Fibrin
 A Measure of Fibrinolytic Pathway
NORMAL VALUE
9-13 SECS
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Causes of prolonged Thrombin Time
• Heparin
• Hypofibrinogenemia
• Dysfibrinogenemia
• Elevated FDPs or paraprotein
• Thrombin inhibitors (Hirudin)
• Thrombin antibodies
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Classifications of bleeding
disorders
• Vessel defects
anaphylactoid purpura
• Platelet disorders
Idiopathic thrombocytopenic purpura
• Factor deficiencies
Hemophilia A, B,
• Other disorders
Oral anticoagulants, liver disease,
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FACTOR DEFICIENCIES
 HEMOPHILIA A (Classic Hemophilia)
• 80-85% of all Hemophiliacs
• Deficiency of Factor VIII (Coded by HEMA gene)
• X-linked disorder
• Inheritence of the disorder occurs with a frequency of 1:5,000 to
1:10,000 males in all populations
• joint and muscle hemorrhage, easy bruising and prolonged
bleeding from wounds
• Lab Results - Prolonged APTT
• Treatment of hemophilia A is accomplished by
infusion of factor VIII concentrate
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 HEMOPHILIA B
(Christmas Disease)
• 10--15% of all Hemophiliacs

10
• Deficiency of Factor IX
• Lab Test - Prolonged APTT
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Diarrhea and pancreatitis
Xia Zhang
Professor
Department of Gastroenterolgy and Hepatology
The Second Affiliated Hospital of CQUMS

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 Normal intestinal movement

 Volume of stool: 200-300g/d
 Frequency: 1 or 2-3 times a day
 Diarrhea
 Volume: > 200g/d
 Frequency: > 3 times a day

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Chronic diarrhea
 Duration: above two months

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Etiology
 Osmotic diarrhea
 Malabsorptive conditions
 Secretory conditions
 Inflammatory conditions
 Motility disorders
 Chronic infections
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Osmotic diarrhea
 Fecal osmolality = Serum osmolality

 Increased osmotic gap
 diarrhea
is caused by ingestion or
malabsorption of an osmotically active
substance
 Common reasons
 lactase deficiency
 laxative abuse
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Malabsorptive conditions
 Major causes
 Small intestinal mucosal diseases
 Intestinal resections
 Lymphatic obstruction
 Small intestinal bacterial overgrowth
 Pancreatic insufficiency
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 Hallmarks of malabsorption
 Weight loss
 Osmotic diarrhea
 Nutritional deficiencies
 Laboratory abnormalities
 Anemia (microcytic or macrocytic,
vitamins or minerals deficiencies)
 Hypoalbuminemia
 Low serum cholesterol
 Hypocalcemia
 Prolonged prothrombin time
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Secretory conditions
 Watery diarrhea
 large volume but normal osmotic gap
 dehydration and electrolyte imbalance
 Causes
 endocrine
tumors (pancreatic carcinoma,
gastrinoma)
 bile salt malabsorption
 cholera
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Inflammatory conditions
 IBD
Crohn’s disease, ulcerative colitis
 Other symptoms
abdominal pain, fever, weight loss, hemato-
chezia
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Motility disorders
 IBS
 Hyperthyroidism
 Surgery
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Chronic infections
 Protozoans giardia
 Entamoeba histolytica
 Cyclospora
 Intestinal nematodes
 AIDS:
microsporida, cryptosporidium,
cytomegalovirus, isospora belli, cyclospora
mycobacterium avium complex
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Acute pancreatitis
 Definition
 Acute
 Chemical inflammatory process
 (an autodigestive process, pancreatic
enzyme)
 Mild and severe
 Mild: edema, self-
self-limited
 Severe: bleeding and necrosis,
complications, high mortality
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Causes and mechanism
 Common causes (70%

(70%--80% of cases)
 excessive alcohol use
 (western country)
 gallstone disease
 (China)
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 Less common causes

 hyperlipidemia (serum triglyceride level)
 hypercalcemia (hyperparathyroidism,
calcification of pancreatic duct, stricture)
 pregnancy (hyperlipidemia
hyperlipidemia))
 obstruction of pancreatic duct (stone, tumor)

 pancreatic cancer, ampullary tumor
 surgery (pancreas, gallbladder, stomach)
 abdominal trauma (blunt or penetrating)

 ERCP (contrast medium, pancreatic duct pressure)
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 infection (AIDS) (ascariasis, clonorchiasis,

mumps, cytomegalo-
cytomegalo-virus, cryptosporidiosis,
cryptococcosis, toxoplasmosis)
 sphincter of Oddi dysfunction
 medications (azathioprine, thiazide diuretics,
sodium valproate)
 idiopathic acute pancreatitis

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Idiopathic acute pancreatitis
 occult gallstone disease (10-

(10-30%)
biliary microlithiasis
gallbladder sludge
 hyperlipidemia
 the sphincter of Oddi dysfunction
 pancreatic cancer, ampullary tumor
 cystic fibrosis (genetic testing)
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Mechanism (pathophysiology)
 Autodigestive process
 Inflammatory media
 Abnormality in pancreatic
microcirculation
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Metabolism of pancreatic enzyme

(exocrine function)
 Active enzymes
 pancreatic amylase
 lipase
 Inactive enzymes: zymogens

 trypsogen
 chymotrypsinogen
 prophospholipase A
 proelastase
 prokininase
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 Normal:
zymogens (duodenum
duodenum/enterokinase)
/enterokinase)
activate
active enzymes
trypsogen (first one),
one), then other zymogens
 Acute pancreatitis:
zymogens (pancreas/
pancreas/enterokinase,
enterokinase,
pancreatic acinar cell/lysosomal
cell/lysosomal hydrolases)
activate
active enzymes
lipase, phospholipase A, kininase, elastase
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lipase, phospholipase A, kininase, elastase
 digest pancreatic and peripancreatic

tissues (proteolysis)
 digest cellular membranes
 vascular damage
 fat necrosis
 edema
 hemorrhage
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The autodigestion theory
 Common channel
 Hypersecretion and obstruction

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Common channel
 Stones, roundworm,
inflammation
(obstruction, sphincter
of Oddi dysfunction, bile
and duodenal juice
reflux)
 Vomit after heavy

alcohol
(duodenal juice reflux)
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Hypersecretion and obstruction

 Hypersecretion
 alcohol
 CCK, secretin￪
secretin￪ pancreatic juice￪
juice￪
 heavy meal
 stimulate pancreatic juice secretion
 Obstruction
 heavy alcohol or meal
 duodenal papilla edema
 heavy alcohol
 more protein in pancreatic juice
 pancreatic stone or tumor
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 Autodigestive process
 Inflammatory media
 PAF (platelet active factor); PG (prostaglandin)
IL--2,6,8; TNF (tumor necrosis factor)

IL
 Abnormality in pancreatic
microcirculation
 (severe pancreatitis)
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Pathological and clinical classification
 Pathological  Pathological
*edematous pancreatitis *necrotizing pancreatitis
 Clinical  Clinical
*mild *severe
(self--limited)
(self (high mortality)
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Clinical findings
 Symptoms
 abdominal pain
 cardinal manifestation (95% pts)
 epigastrium, or left or right, or whole
(severe)
 clonic
 constant, dull and boring
 radiate to the back, the chest and flanks
 worse when supine, lessen when sitting
or fetal position (why?)
 heavy meal or drinking binge triggers
the pain
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 nausea, vomiting
 abdominal distention
 paralysis, hypopotassemia, peritonitis
 fever
 shock (SAP)
 vomiting, blood vessels dilation, GI
bleeding
 hypocalcaemia
 fat necrosis, fat acid
 hyperglycemia
 DM and its complications
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 Signs
 abdominal tenderness
 jaundice
 severe acute pancreatitis:
 muscular guarding
 rebound tenderness
 GreyTurner's sign ( flank discoloration,
due to catabolism of Hb )
 Cullen's
sign ( blue discoloration around
the umbilicus )
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 mass (abscess, pseudocyst)
 ascites
 pleural effusion
 tachycardia
 tachypnea
 hypotension
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Complications
 Acute complications
 secondary infection
 organ failure
 cardiovascular complications
bleeding, vascular resistance decreased
 pulmonary complications
atelectasis, ARDS
 renal complications
acute renal failure:
secondary to cardiovascular collapse and
hypotension acute tubular necrosis
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 GI bleeding
stress ulcer
 Brain complications
pancreatic encephalopathy
 DIC
 MOF
 DM
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 Chronic complications
3 weeks later
 abscesses (in 1 to 4 percent of cases)
 pseudocysts (in 1 to 8 percent of cases)
 chronic pancreatitis (severe)
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 case history, PE findings—

findings—nonspecific
 laboratory tests, abdominal imaging—

imaging—
necessary
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Laboratary tests
 WBC count
 serum amylase
 urine amylase
 lipase
 hepatic function studies
 serum calcium and glucose

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WBC count
 increases (leukocytosis)
 neutrophil counts increase

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Serum amylase
 start increasing: 6 hours after onset
 peaks:12--48 hours
peaks:12
 return to normal: within 7 days
 3 times above the normal

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 nonpancreatic conditions (increase

amylase levels)
serum amylase: less than 3 times above
the normal
 cholangitis
 gastrointestinal perforation or ischemia

 ruptured ectopic pregnancy
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Urine amylase
Rise:: later than serum amylase

Rise
Remains elevated:
elevated: for 7 to 10 days
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Lipase
 increase peak: within 4 to 8 hours of the

onset
 decrease: 8-
8-14 days (amylase: 7 days)
Specificity and sensitivity of lipase measurement

(better than those of amylase in detecting
alcoholic pancreatitis)
pancreatitis)
expensive, complexible, not be widely used
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Hepatic function studies
 hepatic transaminase and serum
bilirubin levels increase (some pts)
 not sufficiently reliable for diagnosing
acute biliary pancreatitis

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Serum calcium and glucose
 hypocalcemia
 fat — fatty acid — fatty acid calcium
 <1.75mmol/L (bad prognosis)
 hyperglycemia
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Radiologic (imaging) studies
 abdominal plain radiographs
 ultrasonography
 computed tomography
 ERCP
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Abdominal plain radiographs
 A gas-
gas-filled duodenum
 secondary to obstruction
 none of the radiologic abnormalities on
plain films can be used for specific
diagnostic purposes
 Subdiaphragmatic free air

 perforation of peptic ulcer
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Ultrasonography
 Suspect biliary diseases

 Advantages
 noninvasive
 inexpensive
 performed at the bedside

 Disadvantage
obscured secondary to bowel gas
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Computed tomography
 The contrast-
contrast-enhanced CT scanning
 provide the best imaging of pancreas and
surrounding structures
 When suggest to take CT scanning?

 other diagnostic studies are inconclusive
 suspect SAP
 assess complications
 following up
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 What can we find from the CT

scanning?
 diffuse or segmental enlargement
 necrosis
 peripancreatic and retroperitoneal edema

 well
well--defined fluid collection (pseudocyst,
abscess)
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Peripancreatic and retroperitoneal edema (large arrows) and

stranding. The pancreas itself (small arrow) appears
relatively normal
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Peripancreatic and retroperitoneal edema. Large non-

non-enhancing areas
of necrosis are visible in the body and neck of the pancreas (arrows)
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a well-
well-defined fluid collection in the retroperitoneum (arrow) just below
the level of the pancreas
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ERCP
 limited role in the management of AP

 be used in pts suspected biliary
obstruction
 be sometimes done to finish
endoscopic sphincterotomy and
remove impacted stone
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Treatment
 Goals
 provide supportive care
 decrease pancreatic inflammation and its
results
 prevent and treat complications
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Mild acute pancreatitis
 Self--limited course
Self
 bed rest
 nooral intake (food, hydrochloric acid,
cholecystokinin, secretin)
 nasogastric suction (not as a routine
treatment, but having vomiting or
obstruction)
 intravenous hydration and electrolytes
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 analgesia (meperidine,, morphine

(meperidine morphine--not used)
used)
 histamine receptor-2 blocker or PPI

receptor-
 antibiotics (quinolones, antibiotics for

anaerobe)
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Severe acute pancreatitis
 the same as those of MAP

 vigorous intravenous hydration and
electrolytes (critical)
 large volume, require careful attention to
monitoring of hemodynamics, urine
output, renal and respiratory function
 acute renal failure:
failure: dialysis
 acute respiratory failure (ARDS):
mechanical ventilation
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 Medications
 decrease pancreatic secretion (atropine,
somatostatin)
 reduce inflammation (indomethacin)
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 Nutritional management
 enteral feeding of an elemental diet into
the jejunum~total parenteral nutrition
(TPN)
 well tolerated
 less risk
 less cost
 decrease septic complications
 helping to maintain the integrity of the
intestinal mucosa
 preventing bacterial translocation across
the intestine
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Intake food
 Oral feedings should not be restarted

until
 any major complications have been
effectively treated
 the pt is free of pain and nausea
 serum amylase or lipase concentrations
have returned to normal
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 Management of gallstones
 ERCP with sphincterectomy and stone
extraction
 surgery
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 Management of pseudocysts
 open internal surgical drainage of the cyst into
the stomach, duodenum, or a Roux loop of
jejunum
 new alternative treatment:
 minimally invasive (laparoscopic) surgery
 percutaneous catheter drainage
 endoscopic drainage
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Chronic pancreatitis
 Definition
 irreversibly histological damage to
pancreas
 development of inflammation, fibrosis, and
destruction of exocrine and endocrine
tissue
 difficult to be diagnosed and classificated
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 Most commonly: alcoholism and idiopathic

causes
 Similar to AP: microlithiasis (implicated in
some cases of chronic pancreatitis)
 Rare: hereditary, hyperparathyroidism,
autoimmune chronic pancreatitis and
obstruction of the main pancreatic duct
caused by stenosis, stones, or cancer
 Rarely:
SAP sufficient pancreatic ductal stenosis
impair drainage chronic pancreatitis
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Symptoms (PMD) and Signs

 P: (pain)
 occasionallyno pain, severe epigastric
pain may last many hours or several days
 M: (malabsorption)
 steatorrhea, passing greasy stools or even
oil droplets, and creatorrhea
 D: (DM)
 glucose intolerance or DM
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Diagnosis
 Laboratory tests
 amylase and lipase (frequently normal)
 markers of inflammation: WBC count (generally
minimally elevated)
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 Imaging tests
 plain x-
x-ray of the abdomen
 calcification (intraductal stones)
 abdominal ultrasound or CT
 abnormalities in size and consistency of the
pancreas
 pancreatic pseudocyst
 dilated pancreatic ducts
 ERCP or MRCP
 abnormalities of the main pancreatic duct
and secondary branches
 EUS
 however, these imaging studies may be
normal in the first few years of disease
PDFelement
Pancreatic function tests

 assess endocrine and exocrine
function
 endocrine
 DM: 2--h PBG level > 11.1 mmol/L; FBG
2
level > 6.66 mmol/L
 exocrine
 the secretin test: unavailable in most
hospitals
 a 72-
72-h test for stool fat: not sensitive for
pancreatic exocrine dysfunction
 more sensitive tests: serum trypsinogen,
fecal chymotrypsin
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Treatment
 a relapse of CP: treatment similar to that of
AP
 eschew alcohol
 IV fluids and fasting (beneficial) – no diet
 small feedings restricted in fat and protein
(to reduce secretion of pancreatic enzymes)
 an H2 blocker or antacids (to reduce acid-
acid-
stimulated release of secretin, which can
increase the flow of pancreatic juice)
 these do not relieve pain, requiring
increased amounts of narcotics
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 medical treatment of CP pain (unsatisfactory),

while endoscopic or surgical treatment (drain
persistent pseudocysts, treat other complications
or relieve pain)
 use of potent pancreatic enzymes recommended

dose of oral pancreatic enzymes: 30,000 U of lipase
(eg, six tablets of pancrelipase) with each meal
 Octreotide
 a long-
long-acting somatostatin analog
 "rest" the pancreas
 pain relief appears minimal
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 Steatorrhea
 with four to six tablets of potent pancreatic extracts
with meals (each contains lipase >= 5000 U)
 If steatorrhea is particularly severe

 medium chain triglycerides
 provided as a source of fat absorbed without
pancreatic enzymes
 reducing dietary fat proportionally
 supplementation with fat-
fat-soluble vitamins (A, D, K)
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 DM
 Oral hypoglycemic drugs rarely used
 Insulin
 Pancreatic cancer
CP: at increased risk for pancreatic
cancer
 an examination for malignancy
 brushing of strictures for cytologic
analysis
 measurement of serum markers (eg, CA
19
19--9, carcinoembryonic antigen)
PDFelement
PDFelement
Case records
 30yrs, pregnant woman (34 weeks), acute

onset
 High fat diet several hours before onset
 Severe epigastric pain,
pain, no intermission,
worse when supine, temporarily relieved by
meperidine
 Lateral crisped position,
position, can’t distinguish the
abdominal signs, can confirm this pain is not
the uterine contraction
PDFelement
 What diagnosis?
 diagnosis
 differential diagnosis
 What tests?
 What treatment?
PDFelement
 Serum amylase: normal
 Urine amylase: 750

750--1000u
 WBC: 14
14××109/L (neu:91%)
 Serum calcium: 1.92 (2.12-

(2.12-2.92)
 Serum glucose: normal
 B ultrasound
 CT scanning
PDFelement
 Diagnosis:
severe acute pancreatitis
 Differrential diagnosis:
 peptic ulcer perforation
 appendix perforation
 intestinal obstruction
 myocardiac infarction
 Treatment:
 surgery
 other treatments
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Thanks!
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Key Points
1.GERD: to control the clinical manifestation , diagnosis ,
differentialdiagnosis and therapeutic principle
Gastritis: Updated Sydney System;

Etiology of chronic gastritis
2.Peptic Ulcer: Complications; Diagnostic tests for HP ; Eradication of H.pylori ;
3.GI bleeding: Common Causes of Upper GI Bleeding ;

Common Causes of Lower GI Bleeding ;
Strategy for diagnosis and management of GI bleeding;
4.Inflammatory Bowel Disease (IBD): Comparison: CD VS. UC

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INTERNAL MEDICINE IMPORTANT
TERMS:
1. Peptic Ulcer Disease - Peptic Ulcer is ulceration which may occur at any site in
the gastrointestinal tract that is exposed to acid-pepsin secretion ("no acid, no
ulcer"). Defects in the gastrointestinal mucosa extend through the muscularis
mucosae into the submucosa or muscularis.
2. Extravascular Hemolytic Anemia - Hemolytic anemia is a disorder in which

the red blood cells are destroyed faster than the bone marrow can produce them.
The term for destruction of red blood cells is hemolysis. In Extravascular
hemolysis, the RBCs are removed from circulation by the phagocytes, in the spleen,
liver or bone marrow.
3. What is the MIC classification of Acute Leukemia?
Classification:
• Acute Leukemia:-
 Acute lymphocytic Leukemia (ALL)
 Acute myelogenous Leukemia or Acute non-lymphocytic Leukemia
(AML，ANLL)
• Chronic Leukemia - Chronic Granulocytic Leukemia (CGL, CML)
• Chronic lymphocytic Leukemia (CLL) - Leukemia uncommon in clinic
4. Primary Hypopituitarism - Impairment of anterior pituitary, leads to

hyposecretion of anterior pituitary hormone which presents itself with target gland
hypo-function. The primary hypopituitarism is caused by anterior pituitary
hypofunction.
5. Somogyi Phenomenon - In Somogyi Phenomenon, there is hypoglycemia in the

night and secondary hyperglycemia. Monitoring midnight blood glucose level
helps to detect the cause of morning hyperglycemia.
6. Updated Sydney System -

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non-atrophic(superficial)
Chronic multifocal atrophic (B)

Gastritis atrophic
autoimmune (A)
special forms
7. Etiology of Chronic Gastritis - Defined as chronic inflammation of gastric

mucosa. Mucosal infiltration of lymphocytes and plasmocytes is a histopathologic
feature. It is most commonly caused by Helicobacter pylori.
ESSAY TYPE:
1. What are the characteristics of epigastric pain in patients with peptic ulcer?
• Chronic: recurrence; weeks, months, years.
• Periodically: Clusters of pain lasting a few days or weeks or months,

followed by pain-free periods of weeks or months
• Rhythmically:
 DU:
 hunger (2-3hours after meals): when acid is secreted in the absence of
food buffer
 At night(11pm-2am)/nocturnal pain : when the circadian stimulation
of acid secretion is maximal
 Relieved when intaking alkali, food, antisecretory agents
 GU:
 Less likely to be relieved by food or antiacids
 More likely to display food provocation(within 1 hour after meals)
• Located at epigastric portion
• Character: dull pain, hungrily pain, gnawing, etc.
• Degree: mild,moderate,severe
• Frequency : paroxysmal , persistent
• Relieve / enhance factors.
2. How to recognize gastrointestinal bleeding? Simply describe the clinical

presentations involved in GI bleeding.
Recognition:
• GI bleeding manifestations
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• Hypovolemia or shock
• Anemia and blood abnormality
• Fever
• Azotemia
Clinical Manifestations:
• Hematemesis - vomiting of red blood/coffee-ground vomitus (Upper GI

bleed)
• Hematochezia - bright red or maroon blood from the rectum (Lower GI
bleed)
• Melena - Shiny, black, sticky, tarry stool (Typically upper GI bleed)
• Chronic occult bleeding - occurs anywhere in the GI tract
3. What are the similarities and differences between Ulcerative Colitis and
Crohn's Disease?
Ulcerative Colitis Crohn's Disease

Pus and blood stool Seldom Common
Distribution Patchy, non-continuous Continuous
Affect rectum Seldom Common
Affect terminal colon Common Seldom
Enteric cavity stenosis Common Seldom
Fistula Common Seldom
Endoscopic appearance Linear ulcer, cobblestone Small ulcer, congestion,
appearance edematous, granular
Histology Inflammation involves all Inflammation confined to
bowel wall layers, mucosa and submucosa,
granulomas crypt abscess
4. How to treat Iron Deficiency Anemia?
• Treatment of the underlying disease

• Iron therapy
• Oral iron therapy
 Preparations: ferrous sulfate tablets, ferrous gluconate
 Iron absorption
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 is enhanced: vitamin C, meat, orange juice, fish

 is inhibited: spinach, tea, milk, coffee
 Duration of treatment: 3 - 6 months
 Expected response: brisk reticulocytosis within 5 to 10 days
• Intramuscular iron therapy
 Indication: intolerance to oral iron or disorder of GI tract
 Dosage: iron to be injected (mg = (15 - Hb/g%/) x body weight (kg) x 3
 Adverse effects: pain at the injection site, anaphylactic reaction (5%)
5. How to treat NHL (Non-Hodgkin Lymphoma)?
The treatment for NHL is:
• Alkalinize urine (sodium bicarbonate)

• Hyper CVAD
• Rituximab
• Auto HSCT, Allo HSCT
• Mesna 600 mg/m2 iv 24-hour*3 days after last dose of cy.
6. How to treat Thyrotoxic Crisis (Thyroid storm)?
• Inhibit the release of hormone from the gland.(solution of potassium iodide )

• Inhibit the biosynthesis of thyroid hormones: Antithyroid drugs in large
doses (600 mg - propylthiouracil or 60 mg methimazole stat and half this
dose q6h)
• Inhibit the sympathetic blockade: Propranolol in large oral doses
• Antagonism to stress: hydrocortisone
• Symptomatic and supportive treatment: fluid replacement, O2, temperature
control, anti-infection
7. Please answer the diagnostic tests for HP?
The diagnostic tests for H. pylori are:
Noninvasive modalities
• Serology: Anti-Hp IgG antibodies

• Carbon 13 or 14 urea breath test (UBT)
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• Stool antigen test
Invasive (endoscopic biopsy require)
• Rapid urease test (RUT)：

 Simplest method when endoscopy is necessary
 Simple; rapid; sensitivity: 80 to 95%; specificity: 95 to 100%
 Invasive; false-negatives possible if testing is done too soon after
treatment with PPI, antimicrobials or bismuth compounds
• Histology
• Culture
8. Please describe the treatment principle of Diabetic Ketoacidosis.
The treatment principle of DKA is:
• Prevention - Education of diabetic patients to recognize early symptoms and

signs of ketoacidosis
• Emergency measures:
 Fluid replacement - Saline solution should be started in the emergency
room as soon as diagnosis is established
 Insulin replacement - Only regular insulin should be used initially in all
cases of ketoacidosis and this should be given immediately after
diagnosis is established.
 Electrolyte replacement - Potassium infusion should be given 2-3 hours
after therapy is started and earlier if the serum potassium level is
inappropriately low. Serum bicarbonate should be given if blood pH is
less than 7.1.
 Treatment of complications like, infection, cardiac failure, renal failure,
cerebral edema, etc.
9. If the fasting plasma glucose is always high, which causes need to be

considered?
• The insulin or oral drug of night is not enough

• Dawn phenomenon-The blood glucose in night is normal, but hyperglycemia
appears in dawn because of the anti-insulin
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• Somogyi phenomenon - There is hypoglycemia in night, and secondary

hyperglycemia. Monitoring mid-night blood glucose help to detect the cause
of morning hyperglycemia.
10. Describe the treatment of Hyperthyroidism.
The therapy for thyrotoxicosis is aimed at decreasing thyroid hormone formation

and secretion. Three different therapeutic approaches are used:
• Antithyroid drugs that inhibit the thyroid peroxidase enzyme involved in

thyroid hormone formation
 PTU and methimazole (MMI), are the preferred initial treatment options
 PTU is most useful for patients with severe thyrotoxicosis and for the
treatment of Graves' disease during pregnancy.
• Supportive therapies
 ß-Adrenergic blocking agents help to provide relief of symptoms such as
tachycardia, tremor, anxiety, and heat intolerance.
 Patients with a history of asthma or congestive heart failure should not
receive ß-Adrenergic blocking agents.
• Radioactive iodine
 RAI therapy (131 I) is used most frequently to treat hyperthyroidism in
adults in the United States
 RAI therapy is preferred for older patients with moderate
hyperthyroidism and thyroid enlargement
• Surgery (Surgical thyroidectomy)
 Surgical removal of a large part of the thyroid (subtotal thyroidectomy)
 Patients must be euthyroid before surgery is undertaken.
11. What is the difference between Severe Aplastic Anemia (SAA) and
Chronic Aplastic Anemia (CAA)?
SAA CAA
Onset Acute and quick Chronic and slow
Anemia Mild at first, aggravated Severe, major symptoms
gradually
Bleeding Severe GI bleeding, Mild petechiae, purpura
encephalorrhagia
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Infection Severe septicemia Mild flu

Prognosis Bad, high mortality Not too bad
12. Please discuss the treatment strategy of Acute Myeloid Leukemia.
The treatment strategy of AML is:
• Supportive care to treat infection, bleeding, etc.

• Chemotherapy
 M3(APL) induction remission therapy - ARTA and Anthracycline
AS2O3
 Induction of remission(non-APL) - DA3+7
 AML with multilineage dysplasia - FAT (Fludarabine and Cytarabine
and Topotecan)
• Consolidation therapy -
 Patients with t(8:21) or inv(16) - high dose cytarabine
 M3 (APL) - ATRA + D or ID AS2O3
 Chemotherapy or Stem cell transplantation
• Bone marrow transplantation
13. Peptic Ulcer complications.
14. Strategy for diagnosis and management of GI bleeding.
• Assessment of patient
 GI bleeding recognition (really GI bleeding?)
 How much blood lost
 Bleeding ongoing or ceased?
• Resuscitation
 Dire consequences are shock.
• Determine the source of bleeding
 Brief history and physical examination
 Upper or lower GI tract
• Urgent vs elective endoscopy
 Urgent endoscopy proposed for all patients
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 Empirical medical therapy before endoscopy

• Specific therapy
 When a definitive diagnosis made
 Medical, endoscopic, angiographic, or surgical
15. Eradication of H. pylori.
16. Causes of upper GI bleed.
• Duodenal ulcer (20–30%)

• Gastric or duodenal erosions (20–30%)
• Varices (15–20%)
• Gastric ulcer (10–20%)
• Mallory-Weiss tear (5–10%)
• Erosive esophagitis (5–10%)
• Angioma (5–10%)
• Arteriovenous malformation (< 5%)
• Gastrointestinal stromal tumors
17. Causes of lower GI bleed.
• Anal fissures
• Angiodysplasia (vascular ectasia)
• Colitis: radiation, ischemic, infectious
• Colonic carcinoma
• Colonic polyps
• Diverticular disease
• Inflammatory bowel disease: ulcerative proctitis/colitis, Crohn's disease
• Internal hemorrhoids
Peptic Ulcer Complications:

1Bleeding (hemorrhage)
①most common cause of UGI bleeding
②The most common cause of ulcer-related death
③symptom&sign.
2 Perforation
①Second most common complication of peptic ulcer
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②Typical clinical presentation:

Acute onset of severe, intolerable abdominal pain:-
-Unremitting & exacerbated by any movement
-Precisely identification of exact time the pain began
Peritoneal irritation sign:-
-Tenderness; Rebound tenderness; Muscle guarding
Bowel sound ↓
Free air underneath the diaphragm(abdominal X-ray)
3 Obstruction
Acute ulcers ⇒ obstruction due to edema ± motor dysfunction (functional
obstruction)
Chronic ulcer ⇒ obstruction occur secondary to scarring of an ulcer in pyloric
channel or duodenum (organic obstruction)
Presentation
gastric retention → frequent vomiting
→ succussion splash
4. Canceration
GU
-: 1%-2% of GU pts
Alert signals:
Chronic GU history
Above 45 ys
Recurrent ulcers
Continuing occult blood test (OB) pisitive
DU
-: No canceration tendency
Eradication of H.pylori?
①PPI–based triple therapy / Bismuth-based triple therapy
Double standard amount of PPI (bismuth subsalicylate) + two antibiotics
Antibiotics include:Clarithromycin 500 mg bid,Amoxicillin 1g bid, Metronidazole
400 mg bid, Tetracycline 500mg bid, Furazolidone 100 mg bid , Fluoroquinolones,
Tinidazole, Rifabutin.
7-14 days, 14 days was the preferred time
②Quadruple-therapy
When Triple-therapy failed
Triple-therapy + PPI / Bismuth subsalicylate
③ Confirmation of Hp cure
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It is important to wait a sufficient time after stopping antibiotics to avoid false-

negative result
-4 wks hiatus is preferable for histology, culture, or urea breath tests;
-8 wks is required for stool antigen test
PPIs should be stopped for 1 wk at least
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Peptic Ulcer
Xinjing Han

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Introduction
• Definition:
– PU is ulceration which may occur at any site in
the gastrointestinal tract that is exposed to acid-
pepsin secretion. (“no acid,no ulcer.”)
– Defects in the gastrointestinal mucosa extending
through the muscularis mucosae into the
submucosa or muscularis
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Histology of stomachwall
epithelium
mucosa lamina propria

muscularis
mucosae
submucosa
muscularis
serosa
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Erosion Acute ulcer Chronic ulcer

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Introduction
• Typical ulcers: Gastric ulcer (GU) ,
Duodenal ulcer(DU)
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Introduction
• Two major causes:
– Hp (helicobacter pylori)
– NSAIDs (nonsteroidal anti-inflammatory drugs)
• Main mechanism:
– Imbalance between aggressive factors and mucosal defenses
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Epidemiology
• Peptic ulcers (PU) occur in up to 10~15% of the
population at some time, and are more common in
men.
• Duodenal ulcers (DU) are more common than
gastric ulcers (GU). In DU and GU, men :
women=4.4~6.8:1 and 3.6~4.7:1 respectively.
• PU occur at different age .DU are about 10 times
more common than GU in young patients, but in
the older age groups the frequency is about equal.
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Etiology and Pathophysiology

1.How ulcers happen:
– When repair and healing mechanisms fail.(GU)
• Impaired healing of mucosal injuries differentiates
ulcer patients from non-ulcer ones exposed to same
risk factors.
– When defense mechanisms are compromised by Hp-
induced inflammation and NSAID-induced reduction of
prostaglandin synthesis,and so on.(DU)
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2. Normal mucosal defense and healing
– Regulation of acid-pepsin secretion:
• balance between neural, endocrine, paracrine, and
autocrine pathways
• involves both stimulatory and inhibitory
mechanisms
– Normal gastroduodenal mucosa has a
remarkable ability to defend and repair itself
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Mucosal defenses
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Mucosal repair and healing
Exogenous factors
Acid and pepsin
Endogenous factors
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3. H.Pylori and Peptic Ulcer
(1) Helicobacter Pylori (HP)
- Found in 1983 by Marshall and Warren.
- Lived under micro-oxygen and acidic condition.
- Main cause of chronic gastrtis and PU.
- Secretion of some inflammatory factors:
urease,vacuolating cytotoxin, lipopolysaccharide
endotoxin, proteinase, lipase and phospholipase A2.
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Barry J. Marshall
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J. Robin Warren
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(2) Two lines of evidence established HP as a crucial

causal factor for development of both DU and GU:
(i)the large majority of DU (＞90%) and GU (＞75%) are
associated with HP.
(ii)Several welldesigned, controlled studies and numerous
other less rigorous trials have consistently indicated that
successfully curing the HP infection predicts a markedly
reduced rate of ulcer recurrence.
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(3)Hp infection destroy the balance between

the aggressive factors and defensive/repairing
factors.
 Hp →inflamation &immune response →damage
the mechanism of mucosal defence and repair.
 Hp →gastrin ↑,acid↑.
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4. NSAIDs and Peptic Ulcer
(1)Mechanism:
① Damage directly gastric mucosal barrier.
② Inhibit the production of endogenous
postaglandin (PG).
• NSAIDs systemically inhibit gastric COX
• Reduces mucosal prostaglandin production
• Limits the ability of the mucosa to defend itself
against injury from superimposed factors
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4. NSAIDs and Peptic Ulcer

(2) Risk factors for NSAID ulcers
– Age: elderly individuals, above 60
– Previous history of ulcers or comlications
– Duration of therapy
– Dose and duration of action and use of multiple
NSAIDs
– Dyspepsia
– Cotherapy with corticosteroids
– Others:Hp infection,smoking,etc.
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5. Acid-pepsin and peptic ulcer
(1)Peptic ulcers formation are finally dependent
upon the acid-peptic activity in gastric juice
(2)Peptic activity is closely linked to gastric pH
– Precursor pepsinogen is converted into active protease
at low pH.
– Pepsin is inactivated when pH is elevated above 4,
accounts for the healing of refractory ulcers when the
pH is elevated above 4.
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(3)Adequate acid secretion is necessary for DU, GU
may occur in low acid concentrations
– Inhibiting acid secretion promotes healing DU and GU
– Average maximal acid secretory to stimulation is
greater in most of ulcers
– Specially in most GU, maximal gastric acid output
(MAO) and basal gastric acid output(BAO) are normal
or less than normal.
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(4)Causes of excess of gastric acid secretion in DU
patients
• Amount of parietal cells↑
mormal : 10 hundred million
DU: 19 hundred million
• Susceptibility of parietal cells to stimulators↑
e.g.:foods, five-peptide gastrin.
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(4)Causes of excess of gastric acid secretion in

DU patients
• Normal feedback inhibitory

Mechanism of gastric acid secretion has some
shortcomings.
• Tension of vagal nerve↑

acid↑,gastrin↑
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6.Other factors and PU

(1)Disturbance of gastric emptying and bile reflux.
(2)Genetic factors
Pre-Hp era: polygenic inheritance
(3) Infections other than Hp

– Herpes simplex virus type 1 (HSV-1)
– Cytomegalovirus (CMV)
(4) Stress and Psychological factors
Regulation
Stress , secretion, motility and mucosal
Psychological factors Vagal nerve
circulation of GI tract.
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(5) Drug exposures

– A number of drugs besides NSAIDs:
 Platelet-active agents
 Steroids
 Anticoagulants
 Sirolimus: patients undergoing transplantation
 Alendronate: prescribed to treat osteoporosis
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(6) Cigarette smoking

– Impairs ulcer healing, promotes recurrences, increases the
risk of complications
– Increased duodenal acid load by increasing gastric
secretion and impairing duodenal and pancreatic
bicarbonate secretion.
(7)Alcohol
– Damage the gastric mucosal barrier
– Stimulates acid secretion
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7. Comorbid ulcers:
• Chronic obstructive pulmonary disease (COPD)
– Peptic ulcers occur in up to 30% of COPD patients
• Cirrhosis
– Prevalence ranging 10-49% in cirrhosis patients
• Renal failure
• Organ transplantation
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Pathology
• Site
GU: Lesser curvature(antrum, incisura angularis )
DU: The anterior wall of duodenal bulb.
• Number: mostly solitary
• Size
GU: less than 2.0cm in diameter
DU: ＜1.5cm
• Depth
Extending through the muscularis mucosa into the
submucosa or muscularis
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1.Symptom
(1) Abdominal pain
Characteristics of pain:
①Chronic:
◆ recurrence;
◆ weeks,months,years.
②Periodically:
◆ Clusters of pain lasting a few days or weeks or months,
followed by pain-free periods of weeks or months
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③Rhythmically
– DU:
• hunger (2-3hours after meals): when acid is secreted in the
absence of food buffer
• At night(11pm-2am)/nocturnal pain : when the circadian
stimulation of acid secretion is maximal
• Relieved when intaking alkali, food, antisecretory agents
– GU:
• Less likely to be relieved by food or antiacids
• More likely to display food provocation(within 1 hour after
meals)
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④Located at epigastric portion

⑤Character: dull pain, hungrily pain, gnawing,
etc.
⑥Degree: mild,moderate,severe
⑦Frequency : paroxysmal , persistent
⑧relieve / enhance factors
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(2). Other dyspepsia symptoms and
complication’s symptoms :
acid reflux , belching, heartburn, epigastric
fullness and discomfort,bloating, early
satiety, nausea and vomiting, hematemesis ,
melena,weight loss, anorexia,etc.
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2. Signs
• Mild, localized epigastric tenderness, often
unremarkable.
• Signs of ulcer complications:

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Complications
1. Bleeding (hemorrhage)
①most common cause of UGI bleeding
②The most common cause of ulcer-related death
③symptom&sign
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Complications
2. Perforation
– Acute onset of severe, intolerable abdominal pain
• Unremitting & exacerbated by any movement
• Precisely identification of exact time the pain began
– Peritoneal irritation sign
• Tenderness; Rebound tenderness; Muscle guarding
– Bowel sound ↓
– Free air underneath the diaphragm(abdominal X-ray)
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2. Perforation
– Acute onset of severe, intolerable abdominal pain
• Unremitting & exacerbated by any movement
• Precisely identification of exact time the pain began
– Peritoneal irritation sign
• Tenderness; Rebound tenderness; Muscle guarding
– Bowel sound ↓
– Free air underneath the diaphragm(abdominal X-ray)
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Complications
3. Obstruction
• Acute ulcers ⇒ obstruction due to edema ± motor
dysfunction (functional obstruction)
• Chronic ulcer ⇒ obstruction occur secondary to scarring
of an ulcer in pyloric channel or duodenum (organic
obstruction)
• Presentation
gastric retention → frequent vomiting
→ succussion splash
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Complications
4. Canceration
• GU
– 1%-2% of GU pts
– Alert signals:
• Chronic GU history
• Above 45 ys
• Recurrent ulcers
• Continuing occult blood test (OB) pisitive
• DU
– No canceration tendency
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Special types of PU
• Silence ulcer: asymptomatic ulcer, more commom in elderly
• The aged ulcer: atypical,GU≥DU
• Complex ulcer :combined gastric and duodenal ulcers
• Pyloric channel ulcer: acid↑,vomit,obstruction
• Postbulbar ulcer :5% of DU,night pain ,back pain,bleeding.
• Giant ulcers: DU>2cm,GU>3cm
• Refractory ulcer: chronic, repeatedly
• Stress ulcer: Cushing’s,Curling’s
• Kissing ulcer : the anterior wall and back wall of duodenal
bulb.
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Pyloric channel ulcer

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Kissing ulcer
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Assistant test
1.Diagnostic tests for HP
⑴ Noninvasive :
· Serology: Anti-Hp IgG antibodies
· Carbon 13 or 14 urea breath test (UBT)
· Stool antigen test
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1.Diagnostic tests for HP
⑵Invasive (endoscopic biopsy required) :

• Rapid urease test (RUT)：
– Simplest method when endoscopy is necessary
– Simple; rapid; sensitivity: 80 to 95%; specificity: 95 to
100%
– Invasive; false-negatives possible if testing is done too
soon after treatment with PPI, antimicrobials or
bismuth compounds
• Histology
• Culture
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Assistant test
2.Fasting serum gastrin level : Gastrinoma
3.Gastric juice analysis: Gastrinoma
4. X-ray barium-Contrast meal
direct sign： niche
indirect sign
– Generally round or oval and may be surrounded by a
smooth mound of edema
– Secondary changes include folds radiating to the crater,
and deformities in the region secondary to spasm,
edema, and scarring
– Although endoscopy has replaced radiology, radiology
can occasionally be useful
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Lateral
Front
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Assistant test
5.Endoscopy and mucosal biopsy
• Provides a sensitive, specific, and safe method for
diagnosing PUD
• Allowing direct inspection and biopsy (gold standard for
determining benign or malignant)
– Benign ulcers：smooth, regular, and rounded edges; a flat
and smooth ulcer base often filled with exudate
– Malignant ulcers: an ulcerated mass that protrudes into
the lumen, surrounding folds that are nodular, clubbed,
fused, or stop short of the ulcer margin, or margins that are
overhanging ,irregular, or thickened
• Biopsy should be performed for all gastric ulcers, as
benign-appearing ulcers may harbor malignancy.
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benign Malignant
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Malignant
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Diagnosis
• Clinical feature(history,symptoms,signs)
• X-ray barium-Contrast meal
• Endoscopy and mucosal biopsy

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• Functional dyspepsia
• Chronic Cholecystitis and
Cholecystolithiasis
• Gastric cancer
• Gastrinoma
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Treatment
1.General measure
Diet
Emotion
Regular life
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Treatment
2. Drug therapy
(1) Eradication of H.pylori
①PPI–based triple therapy / Bismuth-based triple therapy
• Double standard amount of PPI (bismuth subsalicylate)
+ two antibiotics
• Antibiotics include:Clarithromycin 500 mg
bid,Amoxicillin 1g bid, Metronidazole 400 mg bid,
Tetracycline 500mg bid, Furazolidone 100 mg bid ,
Fluoroquinolones, Tinidazole, Rifabutin.
• 7-14 days, 14 days was the preferred time
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(1) Eradication of H.pylori

②Quadruple-therapy
• When Triple-therapy failed
• Triple-therapy + PPI / Bismuth subsalicylate
③ Confirmation of Hp cure
– It is important to wait a sufficient time after stopping
antibiotics to avoid false-negative result
• 4 wks hiatus is preferable for histology, culture, or urea breath
tests;
• 8 wks is required for stool antigen test
– PPIs should be stopped for 1 wk at least
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2. Drug therapy
(2) Antisecreroty drugs:
• H2 receptor antagonists (H2RAs)
• Proton pump inhibitors (PPIs)
• Anticholinergics
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Functional transformation
of secreting parietal cell
(acetylcholine)
Resting parietal cell with collapsed secretory canaliculi cytoplasmic tubulovesicles expressing H+,K+-ATPase
Stimulated parietal cell with formed secretory canaliculi expressing active H+,K+-ATPase pumps.
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(2) Antisecreroty drugs:

Available drugs:
– Cimetidine 800mg/d 4-6w (DU) 6-8w (GU)
– Ranitidine 300mg/d 4-6w (DU) 6-8w (GU)
– Famotidine 40mg/d 4-6w (DU) 6-8w (GU)
– Nizatidine 300mg/d 4-6w (DU) 6-8w (GU)
Available drugs: standard amount
– Omeprazole 20mg/d 4-6w(DU) 6-8w(GU)
– Lansoprazole 30mg/d 4-6w(DU) 6-8w(GU)
– Pantoprazole 40mg/d 4-6w(DU) 6-8w(GU)
– Rabeprazole 10-20mg/d 4-6w(DU) 6-8w(GU)
– Esomeprazole 20mg/d 4-6w(DU) 6-8w(GU)
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2. Drug therapy
(3) Antacids
• Neutralize gastric acid，increases gastroduodenal
pH, rapidly release ulcer pain or discomfort
• Have a long history in the therapy of peptic ulcer,
but inconvenient, requiring multiple doses per day
• Be outmoded for PUD
• Available drugs
– Calcium carbonate antacids
– Magnesium-containing antacids
– Aluminum-containing antacids
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2. Drug therapy
(4) Enhancement of mucosal defenses :
• Sucralfate
• Bismuth
• Prostaglandin E1 analogue (Misoprostol)

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2. Drug therapy
(5) Treatment of NSAID ulcers
• Critical steps in treating NSAID ulcers
– Whenever possible discontinue or at least reduce the NSAID dose
– Search for and cure Hp infection
– Appropriate course of standard ulcer therapy
• Antiulcer drugs:
– PPIs are prefered for ulcer healing in the presence of ongoing
NSAIDs
– Prostaglandins are generally not good alternative for the healing of
NSAID ulcers, only be used for prevention
– H2RAs, sucralfate and antacids are inadequate for treatment of
NSAID ulcers, especially continuing NSAID use
PDFelement
(5)Treatment of NSAID ulcers

• Prevention of NSAID ulcers
 Prostaglandins
– Misoprostol: 200mg, four times daily
 PPIs
– The lowest dose of the least expensive PPI is probably
sufficient
 Not H2RA
– Standard doses do not prevent NSAID-induced ulcers
PDFelement
2. Drug therapy
(6) Refractory and recurrent ulcers
• Most PUD respond to antimicrobial therapy for Hp or
withdrawal of NSAIDs, or heal with usual doses of potent
antisecretory drugs.
• Occasional ulcers are either refractory to treatment or
recur following initial healing.
• Ulcers are considered refractory if unhealed after 8-12wks
of treatment
• Causes of refractory and recurrent ulcers
PDFelement
PDFelement

• Treatment of refractory ulcers
 Reconsider the diagnosis and management
– Confirm: the patient is compliant with an adequate PPI
regimen
– Ensure: continued use of gastrotoxic drugs (NSAIDs)
has been confidently excluded
– Confirm: Hp has been cured and excluded
 If the above causes can be reversed, treatment usually
becomes easy
 For large or densely scarred ulcers, an extended treatment
period may be necessary to prevent recurrences and allow
mucosal remodeling to take place
PDFelement

• Prevention of ulcer recurrence
 Maintenance therapy is indicated to prevent recurrence in high-risk
subgroups
– A history of complications , frequent recurrences, or refractory,
giant or severely fibrosed ulcers
– After eradication of H.pylori
 When maintenance is indicated, sdandard doses of PPIs are reasonable
choices
 Half-dose of H2 Receptor antagonists are alternative choice
– cimetidine 400mg/d
– ranitidine 150mg/d
– famotidine 20mg/d
– usually use for one year
PDFelement
Treatment
3. Surgical
Indication：
☆Complications (bleeding,obstruction,
Perforation,canceration)
☆Refractory ulcers
PDFelement
Treatment
4.Strategy for treatment of peptic ulcer
• Hp infection?
• NSAIDs ?
• Maintenance therapy?
• Surgical?
PDFelement
Gastritis & PU
problem-based learning (PBL)
students divided to eight groups
each group focus on one word to prepare
every group should give a oral report on
next Monday afternoon

PDFelement
1. Abdominal pain And Gastritis / PU ？

Gastritis & PU
PDFelement
2. H.Pylori And Gastritis / PU ？

PDFelement
3. Drinking And Gastritis / PU ？

PDFelement
4.Smoking And Gastritis / PU ？

PDFelement
5.Gastric acid And Gastritis / PU ？

PDFelement
6.Mucosal defence And Gastritis / PU ？

PDFelement
7.Diagnosis And Gastritis / PU ？

PDFelement
8.Treatment And Gastritis / PU ？

PDFelement
THANK YOU ！

Internal Medicine (MERGED) (SEM2) - 2017 Batch

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Remove Watermark Wondershare

The second hospital of

The main subjects

Definition of Endocrinology (A)

• Endocrine: The term endocrine refers to

Definition of Endocrinology (B)

Types of hormone signalization

Pancreas: Adrenal cortex:

Hormone classification (A)

Form the great majority of all hormones.

Polypeptide and protein

Hormone classification (B)

Hormone classification (C)

Hormone classification (D)

Mechanism of hormone action

• There are two types of mechanisms of

Mechanism of hormone action (A)

Most peptide 、protein hormone and catecholamine

Mechanism of hormone action (A)

Figure1.The mechanism of action of peptides

Mechanism of hormone action (B)

Steroid hormones pass

The steroid hormone binds

The receptor bound steroid

The steroid hormone-

Central Roles of the

Regulation of hormone (B)

Regulation of hormone release

Regulation of hormone (C)

Regulation of hormone (D)

 Some stimuli decrease hormone

Regulation of hormone (E)

Regulation of hormone (E)

CRH secretion in hypothalamus

ACTH secretion in pituitary

cortisol secretion in adrenals

Regulation of hormone (E)

Regulation of hormone (E)

Disorders of the endocrine system

Disorders of the endocrine system

Disorders of the endocrine system

Disorders of the endocrine system

Disorders of the endocrine system

 Hyperfunction of Endocrine Glands

Disorders of the endocrine system

 Ectopic Hormone Production

Disorders of the endocrine system

Disorders of the endocrine system

Disorders of the endocrine system

Disorders of the endocrine system

 Secondary Hormone Hypersecretion

Disorders of the endocrine system

 Multiple endocrine deficiencies

Disorders of the endocrine system

cretinism, caused by severe iodine deficiency during pregnancy, is

Epiphyseal plate is closed

purple striae ; plethora ; acne

Treatment of endocrine diseases

Learning main points

The second hospital of

Anatomy and function of the

• The pituitary gland include the anterior lobe,

The main anterior pituitary hormones