2. Lower GI Tract
• Extends from the
duodenojejunal
junction (ligament
of Treitz) to the
anal canal just
above the dentate
line.
3. TERMINOLOGY
• Lower GI Bleeding: hemorrhage into the lumen of the bowel
from a source distal to the ligament of Treitz.
• Bleeding Per Rectum: blood coming though the rectum, doesn’t
indicate the source of blood.
• Rectal Bleeding: blood coming though the rectum, the source
of blood is the rectum.
• Hematochezia: defecation in which feces are bloody.
(Etymology: Gk, haima + chezo, feces) also called BRBPR: bright red blood per
rectum.
4. Ligament of Treitz
• The suspensory muscle of duodenum is a fold of
peritoneum containing thin muscle fibers
connecting the junction between the duodenum,
jejunum, and duodejunal junction to connective
tissue surrounding the superior mesenteric
artery and celiac artery. The suspensory muscle
most often connects to both the third and fourth
parts of the duodenum, as well as the
duodenojejunal flexure, although the attachment is
quite variable.
6. ANATOMY
• The suspensory muscle arises from the right crus of
the diaphragm as it passes around the esophagus,
continues as connective tissue around the stems of
the celiac trunk and superior mesenteric artery,
passes behind the pancreas, and enters the upper
part of the mesentery, inserting into the
duodenojejunal flexure. Here, the muscles are
continuous with the muscular layers of the
duodenum.
7. Functions
• When contracting, it widens the angle of the
duodenojejunal flexure, allowing movement
of the intestinal contents.
• Embryological role in fixating jejunum during
gut rotation.
9. EPIDEMIOLOGY
accounts for approximately 20-33% of episodes of gastrointestinal
(GI) hemorrhage.
with an annual incidence of about 20-27 cases per 100,000
population in Western countries.
LGIB that requires hospitalization represents less than 1% of all
hospital admissions in the United States.
Most of pt are old and already have other problems. with a mean age
at presentation of 63 to 77 years.
Although 80-90% of cases will stop bleeding spontaneously, as many
as 25% will re-bleed either during or after their hospital admission.
reported mortality ranges from 2-4%.
More common in men than in women.
11. Lower Gastrointestinal
Bleeding in Adults
Percentage of Patients
Diverticular disease
•Diverticulosis /diverticulitis of small intestine
•Diverticulosis/diverticulitis of colon
60%
Inflammatory bowel disease
•Crohn disease of small bowel, colon, or both
•Ulcerative colitis
•Noninfectious gastroenteritis and colitis
13%
Benign anorectal diseases
•Anal fissure
•Fistula in ano
•Hemorrhoids
11%
Neoplasia
•Malignant neoplasia of small intestine
•Malignant neoplasia of colon, rectum, and
anus
9%
Coagulopathy4%
Arteriovenous malformations (AVMs)3%
TOTAL100%
12. Lower Gastrointestinal Bleeding in Children and Adolescents
Intussusception
Polyps and polyposis syndromes
•Juvenile polyps and polyposis
•Peutz-Jeghers syndrome
•Familial adenomatous polyposis (FAP)
Inflammatory Bowel Syndrome
•Crohn disease
•Ulcerative colitis
•Indeterminate colitis
Meckel diverticulum
15. Massive Lower GI Bleeding
• Passage of a large volume of red or maroon
blood through the rectum.
• Hemodynamic instability and shock (systolic
blood pressure of less than 90 mm Hg).
• Initial decrease in hematocrit level of 6 g/dl or
less.
• Transfusion of at least 2 unite of PRBC.
• Bleeding that continues for 3 days.
• Significant rebleeding in 1 week.
16. DIVERTICULOSIS
Diverticulum:
•is a saclike protrusion
of the colonic wall
that develops at a
small point of
weakness where the
penetrating vessel
has perforated
through the circular
muscle fibers.
20. Symptoms
Most patients with diverticulosis have few or no
symptoms.
• The most common symptoms of diverticular
disease include:
Bleeding.
Cramping.
Bloating.
Flatulence.
Irregular defecation.(constipation/diarrhea).
21. Diverticula are most
commonly located in
the sigmoid and
descending colon,
Rectum Is not affected
by diverticular disease.
Its related to high
intraluminal pressure.
22. • diverticular bleeding
originates from vasa rectae
located in the sub mucosa,
which can rupture at the
dome or the neck of the
diverticulum.
•
• Although about 75% of the
diverticula occur on the
left side of the colon, right-
sided diverticula are
responsible for
approximately 50-90% of
the bleeding.
• Painless bleeding.
23. • Up to 20% of patients with diverticular disease
experience bleeding, which stops spontaneously in
80% of patients; however, in 5% of patients with
diverticular disease, the bleeding from diverticular
disease can be massive.
24. Complications
• The most common complication is diverticulitis. Which
results in infection in the tissues that surround the
colon.
• Diverticulitis may lead to infection, which often clears
up after a few days of treatment with antibiotics. If the
infection gets worse, an abscess may form in the wall of
the colon.
• Infected diverticula may develop perforations.
• Sometimes the perforations leak pus out of the colon
and form a large abscess in the abdominal cavity, a
condition called peritonitis.
• Fistula Formation.
• Intestinal Obstruction: Scarring caused by infection may
lead to partial or total blockage of the intestine.
25. When diverticulitis-related
infection spreads outside the
colon, the colonic tissue may
stick to nearby tissues. The
organs usually involved are
the bladder, small intestine,
and skin.
The most common type of
fistula occurs between the
bladder and the colon.
This type of fistula affects
men more often than
women. It can result in a
severe, long-lasting infection
of the urinary tract.
Single-contrast barium enema
study demonstrates sigmoid
diverticulitis with a colovesical
fistula. Note the contrast material
in the bladder.
27. Treatment
• Diverticulosis should be treated with high-residue dirt
containing roughage in the form of wholemeal bread
,flour, fruits and vegetables. Bulk formers such as bran
and Isogel may be given. painful disease may require
antispasmodics.
• Diverticulitis is treated by bed rest and IV
antibiotics(cefuroxime and metronidazole).
• The ideal operation is one-stage resection(resection
with end to end anastomosis)
• If there is obstruction, inflammatory edema or
adhesions Hartman’s operation is the procedure of
choice.
29. Meckel's Diverticulum
A true congenital diverticulum, is a small bulge in the small
intestine present at birth. It is a vestigial remnant of
the omphalomesenteric duct
It’s the most common congenital abnormality of the GIT.
A memory aid is the rule of 2s:
2% of the population.
2 feet from the ileocecal valve.
2 inches in length.
2 types of common ectopic tissue (gastric and
pancreatic).
2 years is the most common age at clinical
presentation.
2:1 male: female.
30. Symptoms
• Abdominal pain
• Painless rectal bleeding.
• Vomiting.
• Ulceration (acid production by ectopic gastric
mucosa).
• Small bowel obstruction.
• Perforation.
• Umbilical anomalies.
• N.B: It should e sought when a normal
appendix is found at surgery for suspected
appendicitis.
34. Inflammatory Bowel Disease
• IBD include a group of chronic relapsing disorders
that cause inflammation or ulceration in the small
and/or large intestines. IBD is classified as:
Ulcerative colitis (UC)- causes ulceration and
inflammation of the mucosa of the colon and
rectum.
Crohn's disease (CD) - an inflammation that
extends into the deeper layers of the intestinal
wall, and may affect other parts or layers of the
digestive tract.
35. Epidemiology of IBD
Ulcerative colitis Crohn’s disease
Incidence (US) 11/100 000 7/100 000
Age of onset 15-30 & 60-80 15-30 & 60-80
Male:female ratio 1:1 1,1-1,8:1
Smoking May prevent disease May cause disease
Oral contraceptive No increased risk Relative risk 1,9
Monozygotic twins
concordance
8% 67%
36.
37. UC: Clinical Presentation
• Patients with proctitis usually pass fresh blood or
blood-stained mucus either mixed with stool or
streaked onto the surface of normal or hard stool;
tenesmus is a feature.
• When the disease extends beyond the rectum, blood is
usually mixed with stool or grossly bloody diarrhea may
be noted.
• When the disease is severe, patients pass a liquid stool
containing blood, pus, fecal matter.
• Other symptoms in moderate to severe disease include:
anorexia, nausea, vomitting, fever, abdominal pain,
weight loss.
38. Classification
• UC classified by the extent of involvment
• Proctitis : involvement of the rectum
• Proctosigmoditis : involvment of rectosigmoid
colon
• left sided colitis: involvement of descending
colon and the beginning of transverse colon .
• Pan colitis : involvement of the entire colon
from rectum to the cecum
39. UC
Disease Distribution at Presentation
Ulcerative colitis extends proximally from the anal verge in an uninterrupted pattern
to involve part or the entire colon. The rectum is involved in more than 95% of cases.
46%
37%
17%
40. Histology
Biopsy of the mucosa is considered the
definitive diagnostic test .
The pathology in UC typicaly involve:-
• Distortion of crypt architecture
• Crypt abcess
• Cryptitis
• Inflamatory cell in lamina propria
41.
42. Endoscopic finding :-
• Loss of vascular appearance of the colon
• Erthyma and friability of the mucosa
• Superficial ulceration
• Pseudopolyp
• The colon is affected in continuity so …. No
skip lesion
43.
44. This appearance is typical of colonic
pseudopolyps, or "false polyps." They are
not the kind of true polyps that can lead to
colon cancer, but rather just bands of scar
tissue that have developed due to prior
ulcerations due to severe colitis. As the
ulcers heal they sometimes leave these little
bands of scar tissue inside the colon.
Pseudopolyps do not have the same high
cancer risks as true polyps and usually do
not cause any symptoms
45. • The most common cause of death of patients with ulcerative colitis is toxic megacolon.
46. Treatment
Medical:
supportive, good rehydration, anti inflammatory( steroids,
sulfasalazine , infliximab).
Surgical:
1-Total proctocolectomy with ileostomy.
2- total proctocolectomy ,, ileal pouch ,, pouch anal
anastomosis
indicated when there is:
Massive bleeding, perforation.
Prophylaxis against malignant changes.
No response to medical treatment.
47. Chron’s Disease
•Etiology is unknown ,it appears to be multifactorial
and polygenic.
•Remission and relapses.
• can affect any part of the GI tract, commonest site
is ilieocecal region.
•It is characterized by skip lesions.
•transmural disease affecting all the layers of the
GIT and this will lead to stricture formation.
•granuloma formation, fistula, creeping of fat
,Intestinal obstruction.
48. Crohn’s Disease: Anatomical Distribution
Segmental from mouth to anus…
Small bowel
alone
(33%)
Ileocolic
(45%)
Colon alone
(20%)
Frequency of involvement
Most Least
49. On microscopic examination at high
magnification the granulomatous
nature of the inflammation of Crohn
disease is demonstrated here with
epithelioid cells, giant cells, and many
lymphocytes. Special stains for
organisms are negative.
51. Clinical Presentation
• Abdominal pain, often postprandial.
• Diarrhea, usually watery.
• Rectal bleeding.
• Weight loss.
• Right lower quadrant pain/palpable mass.
• Fever.
• Growth retardation in children.
• Perirectal fistula/fissure/abscess.
52.
53. MRI showing an enterocutaneous fistula
(arrow) in a patient with ileocolic Crohn's
disease.
contrast enema shows a contracted ulcerated
rectum (large arrow), with stricture formation
involving the distal rectum (smaller arrows).
The contrast is seen to fill the vagina (v) via a
very low fistula (thin arrows) connecting the
anal canal with the posterior margin of the
vagina.
54. Treatment
Medical:
anti-inflammatory drugs in acute attacks , prednisone,
immunomodulators such as azathioprine, methotroxate
,natalizumab.
Surgical:
controlling symptoms and treating complications.
Unlike ulcerative colitis, Crohn disease has no surgical
cure.
small bowel obstruction (Stricturoplasty).
perforation, abscesses, fistulae, toxic megacolon, and
massive hemorrhage.
57. Colonic adenocarcinoma develops in 3-5% of patients with
ulcerative colitis mostly in pancolitis and onset of the
disease occurs before the age of 15 years.
58. Indications for Surgery
Majority will need surgery: 78% over twenty
years.
• Intestinal obstruction (most common).
• Intractability/steroid dependence.
• Non-healing fistula/Abscess.
• Toxic megacolon/Free perforation.
• Uncontrollable GI bleeding.
• Severe perianal disease.
• Cancer.
• Growth retardation (children).
• Severe uncontrollable extraintestinal
manifestations.
59. Feature Crohn's Disease Ulcerative Colitis
Involvement of terminal
ileum
Commonly Seldom
Involvement of colon Usually Always
Involvement of rectum Seldom Usually
Peri-anal involvement Commonly Seldom
Bile duct involvement Not associated
Higher rate of Primary sclerosing
cholangitis
Distribution of Disease Patchy Continuous
Endoscopy
Linear and serpiginous (snake-
like) ulcers
Continuous ulcer
Depth of inflammation transmural mucosal
Fistulae Commonly Seldom
Biopsy Can have granulomata No granulomata
Surgical cure
Often returns following removal
of affected part
Usually cured by removal of colon
Smoking Higher risk for smokers Lower risk for smokers
Cancer risk Lower than ulcerative colitis Higher than Crohn's
60. Agiodysplasia
• Agiodysplasia is a small vascular malformation
of the gut. It is a common cause of otherwise
unexplained gastrointestinal bleeding and
anemia. Lesions are often multiple, and
frequently involve the cecum or ascending
colon, although they can occur at other places.
They are usually asymptomatic , but their only
clinical manifestation is bleeding so will be
presenting with anemia , melena or
hematochezia . 80 , 15
61. Pathophysiology
• Histologically, it resembles telangiectasia and development is
related to age and strain on the bowel wall. It is a
degenerative lesion, acquired, probably resulting from chronic
and intermittent contraction of the colon that is obstructing
the venous drainage of the mucosa. As time goes by the veins
become more and more tortuous, while the capillaries of the
mucosa gradually dilate and precapillary sphincter becomes
incompetent. Thus is formed an arteriovenous malformation
characterized by a small tuft of dilated vessels.
• the risk of bleeding is increased in:
1. disorders of coagulation.
2. Heyde's syndrome
62. Diagnosis
endoscopy, either colonoscopy or
esophagogastroduodenoscopy (EGD). Although the lesions
can be notoriously hard to find, the patient usually is
diagnosed by endoscopy. A new technique, pill enteroscopy,
has been a major advance in diagnosis, especially in the small
bowel which is difficult to reach with traditional endoscopy.
With this technique a pill that contains a video camera and
radio transmitter is swallowed, and pictures of the small
intestine are sent to a receiver worn by the patient. Recently,
multiphase CT angiography (without positive oral contrast)
has been shown to play a promising role in the diagnoses of
small and large bowel angiodysplasia, especially when
associated with active hemorrhage
63. • Angiodysplasiae in the small bowel can also be
diagnosed and treated with double-balloon
enteroscopy, a technique involving a long endoscopic
camera and overtube, both fitted with balloons, that
allow the bowel to be accordioned over the camera.
• In cases with negative endoscopic findings and high
clinical suspicion, selective angiography of the
mesenteric arteries is sometimes necessary, but this
allows for interventions at time of the procedure. An
alternative is scintigraphy with red blood cells labeled
with a radioactive marker; this shows the site of the
bleeding on a gamma camera but tends to be unhelpful
unless the bleeding is continuous and significant.
64. Treatment
• If the anemia is severe, blood transfusion
• Endoscopic treatment is an initial possibility, where cautery or
argon plasma coagulation (APC).
• angiography and emolization.
• Resection of the affected part of the bowel may be needed if the
other modalities fail
• If the bleeding is from multiple or inaccessible sites, systemic
therapy with medication may be necessary. First-line options
include the antifibrinolytics tranexamic acid or aminocaproic acid.
Estrogens can be used to stop bleeding from angiodysplasia.
Estrogens cause mild hypercoaguability of the blood.
• In severe cases or cases not responsive to either endoscopic or
medical treatment, surgery may be necessary to arrest the
bleeding.
65.
66. Mesenteric ischemia
• Definition :Decreased intestinal blood flow results in ischemia
and subsequent reperfusion damage at the cellular level that
may progress to the development of mucosal injury, tissue
necrosis, and metabolic acidosis.
• Occurs in old ages 60 years .
• can be divided into arterial and venous etiologies, but more
are arterial causes .
• acute and chronic ischemia.
• The superior mesenteric vessels are most likely to be affected
by embolisation or thrombosis , but inferior mesenteric
vessels is usually silent because of a better collateral
circulation .
67. Acute mesenteric ischemia
• Three progressive phases of ischemic colitis have been described :
1. A hyper active phase occurs first, in which the primary symptoms
are severe abdominal pain and the passage of bloody stools. Many
patients get better and do not progress beyond this phase.
2. A paralytic phase can follow if ischemia continues; in this phase,
the abdominal pain becomes more widespread, the belly becomes
more tender to the touch, and bowel motility decreases, resulting
in abdominal bloating, no further bloody stools, and absent bowel
sounds on exam.
3. Finally, a shock phase can develop as fluids start to leak through
the damaged colon lining. This can result in shock and metabolic
acidosis with dehydration, low blood pressure, rapid heart rate,
and confusion. Patients who progress to this phase are often
critically ill and require intensive care.
68. • abdominal pain in 95%.
• nausea in 44%
• vomiting in 35%
• diarrhea in 35%
• heart rate > 100 in 33%
• blood per rectum in 16%
• Constipation in 7%
69. • Etiology :
• Acute mesenteric arterial embolism :
• Cardiac emboli - myocardial infarction, mitral stenosis and atrial
fibrillation, or septic emboli from valvular endocarditis .
• Emboli from fragments of proximal aortic thrombus due to a ruptured
atheromatous plaque.
• Atheromatous plaque dislodged by arterial catheterization or surgery (eg,
aortic aneurysm resection).
• Acute mesenteric arterial thrombosis
• Atherosclerotic vascular disease (most common).
• Aortic aneurysm.
• Aortic dissection.
70. • Nonocclusive mesenteric ischemia:
• Hypotension from CHF, MI, sepsis, aortic insufficiency, severe liver or renal
disease, or recent major cardiac or abdominal surgery.
• Vasopressors.
• Cocaine.
• Mesenteric venous thrombosis:
• Hypercoagulability: from protein C and S deficiency,antithrombin III
deficiency, abnormal plasminogen, polycythemia vera (most common),
thrombocytosis, sickle cell disease, factor V Leiden mutation, pregnancy,
and oral contraceptive use.
• Tumor causing venous compression.
• Infection, usually intra-abdominal (eg, appendicitis, diverticulitis, or
abscess).
• Venous congestion from cirrhosis (portal hypertension).
71. Diagnosis
• Blood tests
1. White blood cell count >10.5 in 98%
2. Lactic acid elevated in 91%
• During endoscopy
• Plain x-ray
Plain X-rays are often normal or show non-specific findings.
• Computed tomography (Mesenteric edema,Bowel dilatation,Bowel wall thickening,Intramural
gas)
• Angiography
As the cause of the ischemia can be due to embolic or thrombotic occlusion
of the mesenteric vessels or nonocclusive ichemia, the best way to
differentiate between the etiologies is through the use of mesenteric
angiography. Though it has serious risks, angiography provides the
possibility of direct infusion of vasodilators in the setting of nonocclusive
ischemia
72. Treatment
• NG tube decompression, angiogram for diagnosis and treatment,
heparin anticoagulation. Papaverine to decrease arterial
vasospasm.
• "Surgical revascularisation remains the treatment of choice for
mesenteric ischaemia, but thrombolytic medical treatment and
vascular interventional radiological techniques have a growing
role".
• If the ischemia has progressed to the point that the affected
intestinal segments are not savable, a bowel resection of those
segments is called for. Often, obviously dead segments are removed
at the first operation, and a second-look operation is planned to
assess segments that are borderline that may be savable after
revascularization.
73. Chronic mesentric ischemia
• usually results from long-standing atherosclerotic disease of 2
or more mesenteric vessels ( 95% of patients ).
• Clinical features :
• Postprandial pain, generally epigastric or periumbilical.
• Fear of eating (sitophobia).
• Weight loss.
• Non-specific symptoms : nausea , vomiting , diarrhea , constipation .
• Etiology :
• Factors that predispose to atherosclerosis are associated with increased
risk for CMI : smoking , hypertension , D.M. , Hypercholesterolemia.
74. Management :
management of LGIB has 3 components, as
follows:
Resuscitation and initial assessment
Localization of the bleeding site
Therapeutic intervention to stop bleeding at
the site
75. Resuscitation :
2 large-bore intravenous (IV) catheters and isotonic
crystalloid infusions.
Meanwhile, rapid assessment of vital signs” H.R, P.R, B.p,
urine output”
- Orthostatic hypotension (ie, a blood pressure fall of >10
mm Hg) is usually indicative of blood loss of more than
1000 mL.
lab (CBC) , electrolyte levels, and coagulation studies,
blood type and cross-matched.
Red cell transfusion should be considered after loss of 30%
of the circulating volume.
the patient may require invasive hemodynamic monitoring
to direct therapy.
The Pt. must be kept NPO.
76. Initial Assessment :
Signs of hemodynamic compromise include postural
changes with dyspnea, tachypnea, and tachycardia.
- An orthostatic drop in systolic blood pressure of more
than 10 mm Hg or
- An increase in heart rate of more than 10 beats per
minute
are indicative of at least 15% of blood volume loss.
A hematocrit level of less than 18% or a decrease of
about 6% is indicative of significant blood loss that
requires blood transfusions.
77. Localization of the Bleeding Site
• In about 10% of patients presenting with LGIB,
the source of bleeding is from the upper
gastrointestinal (GI) tract.
• Some patients with LGIB should have a
nasogastric (NG) tube placed, and if the aspirate
or lavage does not show any blood or coffee
ground–appearing material but dose show bile,
bleeding originating from the upper GI tract is
unlikely. In case of high suspicion, obtain an
esophagogastroduodenoscopy (EGD) evaluation.
78. Cont’ :
• In patients who are hemodynamically stable
with mild to moderate bleeding or have had a
massive bleed that has stabilized.
Colonoscopy should be performed initially.
• Once the bleeding site is localized, therapeutic
options include coagulation and injection with
vasoconstrictors or sclerosing agents.
79. Colonoscopy
• In cases of diverticular bleeding, bipolar probe
coagulation, epinephrine injection, and
metallic clips may be used.
• In cases of angiodysplasia, thermal therapy,
such as electrocoagulation or argon plasma
coagulation, is generally successful.
• Neoplastic bleeding due to polyps requires
polypectomy.
80. Cont’
• In patients in whom the
1. bleeding site cannot be determined based on
colonoscopy and
2. in patients with active sever LGIB,
Angiography with or without a preceding
Radionuclide Scan should be performed to
locate the bleeding site as well as to intervene
therapeutically.
- In association with Vasoconstrictive Therapy
81. Vasoconstrictive Therapy:
• Initially, vasoconstrictive agents, such as vasopressin
(Pitressin), epinephrine with propranolol.
• Intra-arterial vasopressin infusions begin at a rate of 0.2
U/min, with repeat angiography performed after 20
minutes.
• The bleeding stops in about 91% of patients receiving intra-
arterial vasopressin but recurs in up to 50% of patients
when the infusion is stopped.
• If bleeding persists, the rate of the infusion is increased to
0.4-0.6 U/min.
• Once the bleeding is controlled, the infusion is continued in
an intensive care setting for 12-48 hours and then tapered
over the next 24 hours.
82. Complications of vasopressin infusion include:
- myocardial ischemia, arrhythmia,
hypertension, bowel ischemia, peripheral
vascular ischemia, and antidiuretic effect
83. Surgery :
• In patients with rebleeding after all the measures have
been taken, surgery should be considered.
- subtotal colectomy is recommended for the
management of colonic hemorrhage that is
uncontrolled by other procedures or recurrent
bleeding is present.
- Segmental bowel resection (following precise
localization of the bleeding point )is a well-accepted
surgical practice in hemodynamically stable patients.
- Total colectomy is considered if bleeding is from
unknown site “ R/O : S.I, U.G.I, Rectal causes”
84.
85. Distinguishing features between UC and CD
Feature Crohn's Disease Ulcerative Colitis
Terminal ileum
involvement
Commonly Seldom
Colon involvement Usually Always
Rectum involvement Seldom Usually
Peri-anal involvement Commonly Seldom
Bile duct involvement Not associated Higher rate of PSC
Distribution of Disease Patchy areas of inflammation Continuous area of inflammation
Endoscopy
Linear and serpiginous (snake-like)
ulcers
Continuous ulcer
Depth of inflammation
May be transmural ,deep into
tissues
Shallow, mucosal
Fistulae Commonly Seldom
Biopsy Can have granulomata No granulomata
Surgical cure Often returns following surgery Usually cured by removal of colon
Smoking Higher risk for smokers Lower risk for smokers(Protective)
Cancer risk Lower Higher