Beri beri

Etiology
1- Deficiency of vitamin B1 (Thiamin)
2- Pathogenesis
- Accumulation of pyruvic and lactic acid → peripheral VD → failure to
form TPP (thiamine pyrophosphate which is a coenzyme for the
decarboxylation of pyruvate to acetyl coenzyme A – bridge between
anaerobic glycolysis and krebs cycle) → hyperdynamic circulation
- So, the cells can't metabolise glucose aerobically, this is likely to affect
the nervous system first since it depends entirely on glucose
3- Risk factors
- High CHO diet
- Heavy alcohol intake
- Intravenous glucose infusions
4- The word "beri beri"
- Comes from Sinhalese language and means I cannot said twice
signifying that the patient is too ill to do anything
Clinical features
1- Peculiar changes in peripheral nervous system, GIT and CVS:
- Peripheral polyneuritis with numbness, tender calf muscles and muscle
wasting (dry beri beri)
- Edema
- Palpitation and high cardiac output heart failure
- GIT disturbances e.g. anorexia, nausea and vomiting
2- Wernicke's encephalopathy
- Acute onset of confusion, ophthalmoplegia and ataxia
- Responds to thiamin, but memory disorders (Korsakoff's psychosis)
may persist which characterized by impaired memory + confabulations

1
Diagnosis
1- Measurement of transketolase activity in red cells (TPP is a coenzyme for
transketolase)
2- Elevated plasma pyruvate and lactic acids (in acute form)
Treatment
1- Diet rich in thiamin
- Wheat, nuts, oatmeal, white bread, legumes and yeast
2- Thiamin 50 mg IM for 3 days then 10 mg 3 times daily oral until convalescence
is established
3- Treatment of Wernike's encephalopathy
- It should be treated without delay by 50 mg thiamine IV followed by 50
mg IM daily for a week

Pellagra

Etiology
1- Deficiency of niacin (nicotinic acid)
2- Source and absorption
- Liver, kidney, fish, meat, peanuts, yeast and coffee
- Additional source is by synthesis from the amino acid tryptophan in
body (60 mg tryptophan can give rise to 1 mg nicotinic acid)
3- Pellagra occurs in maize eating population due to
- Maize is deficient in nicotinic acid
- Maize is deficient in tryptophan
- Maize contains nicotinic acid antagonists
Clinical features
1- Skin (erythema resembling severe sunburn)
- Affects skin exposed to sunlight and subjected to pressure, heat and
other types of trauma or irritation e.g. face, neck, dorsal surfaces of the

2
 wrist and forearms. Also the skin over the greater trochanter can be
affected
- The skin is erythematous, later it becomes brown, thickened, rough and
scaly
2- Alimentary tract
- Diarrhea
- Anorexia, nausea, vomiting and abdominal pain
- Achlorhydria (40% of cases)
- Stomatitis with reddening of the tip and margin of tongue (glossitis)
3- Nervous system
- Delirium → in the acute form of the disease
- Dementia → in the chronic form of the disease
- Other manifestations like SCD but without posterior column tract lesion
 Peripheral neuropathy mainly sensory (glove and stoke
hypothesia)
 Early paraplegia and late quadriplegia due to pyramidal tract
degeneration
- The presence of pyramidal tract lesions with peripheral neuropathy →
exaggerated knee reflexes with lost ankle jerks
- The distribution of vibration sense by tunning fork can discriminates
deep sensory loss due to PC tract lesion (sensory ataxia) from deep
sensory loss due to peripheral neuropathy
Dermatitis, diarrhea, delirium and dementia

Diagnosis
1- Assay of RBCs nicotinic acid
Treatment
1- Diet rich in niacin
2- Nicotinamide 100 mg / 6 hrs orally

3
Traveler's diarrhea

Definition
Defined as 3 or more unformed stools per day in a person traveling to a developing
nation
Etiology
1- Mode of infection → feco-oral through contaminated water or food
2- Pathogens
- Enterotoxigenic E.coli is the most common (1/3 of cases)
- Salmonella, shigella, campylobacter and enteroinvasive E.coli
- Viral causes include noroviruses and rotavirus
- Parasites are less common and usually seen in long term travelers
Clinical features
1- Diarrhea, anorexia, nausea, vomiting and cramping abdominal pain can occur
2- May be low grade fever
3- Postdiarrhea IBS may develop in some patients
4- The illness is self limited, usually lasting 3-5 days
Treatment
1- Fluid replacement is important
2- Symptomatic treatment
- Loperamide or bismuth subsalicylate is effective when there is no
bloody stool or fever > 38.5 C
3- Antibiotic treatment
- Usually not required
- Indications
 Severe symptoms (> 4 stools in 24 h) associated with fever,
blood, mucus or pus in stool
- Drugs
 Ciprofloxacin 500 mg bid for 3 days is the usual treatment

4
  In fluoroquinolones resistant campylobacter (southeast Asia and
Indian subcontinent) → Azithromycin 1 g PO single dose
 Recently, Rifaximin, a nonabsorbable gut specific antibiotic has
been approved by the FDA for the treatment of traveler's diarrhea
at a dose of 200 mg one tablet t.i.d. for 3 days
4- Prophylaxis
- Antibiotic prophylaxis breeds resistance and is recommended only for
patients at high risk for morbidity and mortality from diarrhea or
persons who are on a special "business" trip [should be restricted to 2-5
days only]
- Administration
 Start drugs at the 1st day of travel
 Continued for 1-2 days after returning home
 No drug should be taken > 3 weeks
- Drugs and dosage
 Bismuth subsalicate → 60 mL q.i.d.
 Doxycycline → 100 mg daily
 Trimethoprim/sulfamethoxazole → 160-800 mg daily
 Ciprofloxacin → 500 mg daily
 Norfloxacin → 400 mg daily
 Aztreonam → 100 mg daily
5- Prevention
- Avoid raw fruits, vegetables, water and ice cubes
- All water should be boiled or bottled

5
Acute infectious diarrhea

Definition → see diarrhea

Causes → see acute diarrhea
Inflammatory Non-inflammatory
(The majority of cases )
Symptoms Abdominal pain, tenesmus, fever and chills Abdominal pain, nausea, vomiting.
Fever is not a major feature.
Stool Frequent, small volume, blood-stained with pus Less frequency, voluminous, watery,
& mucous no blood or fecal leukocytes
Site Distal ileum & colon Proximal small intestine
Mechanism Enterocyte invasion, mucosal damage & Osmotic or secretory [enterotoxic
inflammation [exudative] bacterial, viral or non invasive
parasitic process]
Causes Bacterial → Shigella, nontyphoid salmonella, Viruses → rotavirus, norovirus and
campylobacter, shiga toxin producing E.coli, coronavirus
C.difficile Bacterial → E.coli (enterotoxigenic
Less commonly → Aeromonas spp., noncholera and enteroaggregative or
vibrio and yersinia enterocolitica enteroinvasive), salmonella,
Protozoa → E histolytica and B. coli campylobacter, C. perfringens,
Helminthes → Schistosoma spp bacillus cereus, vibrio (cholera and
parahaemolyticus)
Protozoa → giardia,
cryptosporidium, cyclospora,
microsporidia, isospora
Helminthes → strongyloids

Risk factors for death

1- Malnutrition
2- Extremes of age
3- Immunosuppression
4- Development of complications
- Dehydration
- Acidosis
- Electrolyte disturbances
- Acute renal failure
- Sepsis
- Pneumonia
6
 - Hemolytic uremic syndrome
Differential diagnosis [non-infectious causes of diarrhea] as
1- Drugs
2- Food allergy
3- Inflammatory bowel diseases
4- Malabsorption e.g. celiac disease
5- Irritable bowel syndrome
6- Diverticular disease
7- Hyperthyroidism
Investigations
1- In nonhospitalized patients with mild to moderate symptoms (< 5 stools/d)
and no fever, nausea, vomiting or cramps
- Supportive therapy is indicated
- Stool culture is not helpful (but may help to identify outbreaks)
2- Stool examination for leukocytes and occult blood
- Indicated in any patient with fever and moderate to severe diarrhea esp.
if bloody
- Numerous leukocytes → invasive enteric pathogen
- Mononuclear cells → typhoid fever or amebic dysentery
3- Stool examination for ova and parasites
- Indicated in all patients who have had diarrhea > 2 weeks, have traveled
to developing countries, drink well water, have sex with men or are HIV
positive
- Special stains are needed for amebic trophozoites
- Cryptosporidium associated with community swimming pools
4- Stool culture
- Indicated if stool positive for leukocytes
- Identify common bacterial pathogens as campylobacter, salmonella and
shigella spp.

7
 - The 3 day role → patients who develop diarrhea after 3 days of
hospitalization are unlikely to have a non C. difficile bacterial or
parasitic cause of diarrhea and stool for cultures and/or ova and
parasites is not recommended
- Exceptions are → age ≥ 65 y, comorbid diseases, neutropenia and HIV
infection, who may need culture despite diarrhea onset ≥ days after
hospitalization
5- Stool toxin assays
- Detect clostridium difficile toxin
- Detect shiga like toxin
6- Stool antigen assays detect
- E.histolytica, giardia, isospora and cryptosporidium
7- Blood culture
- In severely ill patient suspected to have salmonellosis
- In any immunocompromised patients
8- Colonoscopy and biopsy
- Diagnose amoebiasis
- Exclude IBD
9- Electrolytes assay
Treatment
1- Fluid and electrolyte replacement → the mainstay of therapy
- Oral rehydration solution in mild cases effective in repletion of fluid
losses and prevention of hypoglycemia
- IV fluids preferably ringer lactate is indicated in severe cases with
dehydration
2- Diet
- Cereals, starches, lactose free diet, crackers and soup
3- Zinc supplementation → beneficial esp. in children (14 days)
4- Adsorbents

8
 - E.g. Kaopectate, aluminum hydroxide don't influence the course of the
disease but help produce solid stools
5- Antisecretory agents
- Drug → Bismuth subsalicylate (pepto-Bismol)
- Effect → block the secretory effects of v.cholerae, enterotoxigenia
E.coli and shigella. Also can prevent infection by these pathogens if
given prophylactically
- Therapeutic dose → 30 mL every 30 min for 8 doses
- Prophylactic dose → 60 mL or 2 tablets q.i.d. for the duration of
prophylaxis e.g. for travelers
6- Opiate derivatives (antimotility agents)
- Contraindicated in patients with
 Fever
 Bloody diarrhea
 Systemic toxicity
- May be used in acute diarrhea with moderate symptoms (< stools/day)
or in chronic diarrhea
- Drugs → loperamide and diphenoxylate
- Loperamide (Imodium) has 2 advantages over lomotil in that it does not
contain atropine and it has fewer central opiate effects
7- Antimicrobial agents
- Indications
 Severe or bloody diarrhea associated with fever and systemic
toxicity
 Traveler's diarrhea → rifaximin ®
 Antibiotic associated diarrhea → metronidazole ± vancomycin ®
[other drugs include cholestyramine 4 g PO t.i.d. for 7 days or
rifaximin 200 mg PO bid for 3 days]
 Protozoal infection → metronidazole ® (amoeba and giardia)
 Cholera → doxycycline ®

9
  HIV patients → cotrimoxazole, metronidazole and nitazoxanide
- Drugs → given according to specific pathogen detected by stool culture
- Empiric therapy must have activity against shigella and campylobacter
 Ciprofloxacin → 500 mg PO bid for 3 days (also effective against
E.coli and - salmonella - 5-7 days)
 Azithromycin → single dose of 1 g PO is recommended for
quinolone resistant campylobacter infection (or erythromycin 250
mg PO q.i.d. for 5-10 days)
- Trimethoprim/sulfamethoxazole
 160/800 mg PO bid for 5 days → in shigella, E.coli
 160/800 mg PO bid for 10 days in salmonella
- 3rd generation cephalosporins, chloramphenicol, amoxicillin
 Esp. important in salmonella infection
- Contraindications
 Enterohemorrhagic E.coli (as O157:H7) → may increase the risk
of HUS

11
Leprosy

Key facts

1- Leprosy is a chronic granulomatous disease affecting mainly the skin, the

peripheral nerves, mucosa of the upper respiratory tract and also the eyes and
characterized by:
- Anaesthetic skin lesions
- Peripheral neuropathy
- Peripheral nerve thickening
2- The clinical form of the disease depends on cell mediated immunity
- High levels of CMI → tuberculoid leprosy
- Absence of CMI → lepromatous leprosy
3- Leprosy is curable and treatment provided in the early stages averts disability.
4- Untreated, leprosy can cause progressive and permanent damage to the skin,
nerves, limbs and eyes.
Causative organism

1- Mycobacterium leprae
2- Obligatory intracellular acid fast bacilli multiplying mainly inside the
macrophages of the skin and nerves
3- It has a highly resistant cell wall composed of lipids, carbohydrates and proteins
[phenolic glycolipid M. leprae is species specific]
Source of infection
1- Nasal discharge or ulcerating skin lesions → either via inhalation or through the
skin (break in normal skin)
2- Breast milk
3- Transplacental

11
Pathogenesis
1- Probably defective cell mediated immunity specific for leprosy
2- The earliest tissue response → is a non specific inflammatory cellular reaction
(indeterminate) which if not overcome at this stage → will pass into any of the
3 determinate types depending on the cell mediated immunity response of the
individual
Classifications and types
1- Indeterminate type
- Skin macule is the earliest manifestation → small ill defined
depigmented lesion which may occur anywhere in the body
- No sensory abnormality
- Skin lesion usually heals spontaneously
2- Tuberculoid type
- Immunity → high immunity keeping the infection localized in the
nerves and dermis
- Pathology → non caseating epithelioid cell granuloma
- Bacilli → very scarce and so it is probably non infectious
- Lepromin skin test → positive
- Clinically
 Anaesthetic macules with raised edges or plaques
 They are depigmented in black races but reddish or coppery in
white skins
 Thickened nerves are characteristic
 The commonly affected nerves are → ulnar (claw hand), median
(Ape hand), superficial radial, common peroneal and great
auricular nerves with corresponding motor and sensory changes
3- Lepromatous type
- Immunity → no cell mediated immunity (represents the other extreme
of clinicopathological spectrum)
- Lepromin skin test → negative

12
 - Bacilli → fill the macrophages (this is the infectious form of the
disease)
- Pathology → macrophages are full of bacilli and proliferate in the
dermis around the nerves and blood vessels and gradually invade the
peripheral nerves, mucous membranes of the respiratory tract, eyes,
muscles and the small bones of the hand, feet and face
- Clinically
 Skin lesions → numerous, symmetrically distributed and can be
macular, plaque form or nodular
 The skin becomes progressively thickened from the lepromatous
infiltration with characteristic swelling of the ear-lobes, lips and
nose and deepening of the facial lines (Leonine face)
 Nasal congestion and discharge
 Keratitis
 Widespread peripheral neuritis and loss of tissue and eatening of
bones due to anaesthesia leading to disfigurement and ambutation
may occur
4- Borderline or dimorphic type
- Falls between the 2 types with the host reaction varying from near
tuberculoid to near lepromatous depending on the immune status of the
patient and may vary in the same patient from time to time
- Clinically → lesions show a mixed picture of tuberculoid and
lepromatous types with either type dominating depending on the
immune status
Diagnosis
1- Clinical diagnosis
2- Bacteriological diagnosis
- Skin slit smear → for lepromatous and borderline cases
- Nasal scraping → for lepromatous and borderline cases
3- Histopathological diagnosis

13
 - Skin biopsy → including the full depth of the dermis
- Nerve biopsy → from the thickened nerves
4- Immunological diagnosis
- Lepromin skin test (non specific antigen)
 Highly positive in tuberculoid leprosy
 Negative in lepromatous leprosy
- ELISA for detection of specific antibody responses in leprosy patients
- Dot ELISA for detection of antigenaemia
Main clinical characters of polar leprosy [Ridley-Jopling classification]
Tuberculoid Lepromatous
Skin and nerves
Number and distribution One or a few sites, asymmetrical Widely disseminated
Skin lesions
Definition
Clarity of margin Good Poor
Elevation of margin Common Never
Colour
Dark skin Marked hypopigmentation Slight hypopigmentation
Light skin Coppery or red Slight erythema
Surface Dry, scaly Smooth, shiny
Central healing Common None
Sweat and hair growth Impaired early Impaired late
Loss of sensation Early and marked Late
Nerve enlargement and Early and marked Late
damage
Bacilli (bacterial index) Absent (0) Many (5 or 6 +)
Natural outcome Healing Progression

Type 1 (reversal) reactions

Cause → sudden delayed hypersensitivity towards M.leprae antigens in skin and
nerve
Risk
1- All borderline patients (BT, BB, BL-in 30% of cases-) and tuberculoid type
2- Women in the postpartum period
Clinical features
1- Onset → the peak time during the first 2 months of treatment

14
 2- The previously flat lesions suddenly become hot, painful, tender, erythematous
and raised (swelling)
3- Pain and tenderness of peripheral nerves
4- Loss of sensory and motor function
5- Rapid severe nerve damage may occur, so patients must be warned about
symptoms and advised to return for treatment if they develop new weakness or
numbness
Treatment
1- Prednisolone 40 mg/day reducing by 5 mg/day every month (must be given to
all reactions esp. those with acute neuritis)
2- Physiotherapy for affected hand, foot and eye muscles

Erythema nodosum leprosum reaction

Cause → immune complex deposition (→ acute vasculitis), T cell dysregulation and
overproduction of TNF
Risk → affects 50% of LL (lepromatous leprosy) and 10% of BL patients

Clinical features
1- Onset → usually starts in the first year of chemotherapy and may relapse
intermittently over several years
2- Systemic illness with malaise, fever and ↑ TLC and ESR
3- Wide spread erythema nodosum (painful red skin swellings- crops of tender
nodules which may pustulate)
4- Neuritis, iritis, arthritis, orchitis and nephritis
5- Lymphadenopathy and renal disease
Treatment
1- Hospitalization for severe cases
2- Both physical and mental rest
3- Salicylates 600 mg 4 times/day
4- High dose prednisolone 60-80 mg/day or
15
 5- Thalidomide
- The drug of choice in male and postmenopausal females
- Very effective in relieving the symptoms and signs and give better long
term control and avoids the adverse effects of long term steroid
treatment
- Dose → 100 mg /6 hrs daily for 48-72 hours then the dose reduced to
maintenance of 100 mg daily (usually the reaction controlled within 48-
72 hours)
6- Increasing dose of clofazimine up to 300 mg daily for 3 months may also ↓
inflammatory responses
7- Chloroquine → has anti-inflammatory effect. Dose 150 mg base 3 times/day for
2 weeks
8- Colchicine 0.5 mg twice/day for 1-2 months
9- Iritis → 1% atropine and 1% steroid eye drops
10- Continue antileprosy drugs and reassured the patient that the reaction will settle

Neuritis
1- Onset → >60% of patients who present with nerve damage at diagnosis are at
risk of developing further nerve damage during and after treatment esp. during
the first 12 months of treatment
2- Acute and chronic nerve inflammation that may occur without evidence of
either a type 1 or type 2 reaction
3- Silent neuropathy → development of functional deficit of a major nerve
without a manifest neuritis [nerve function should be checked carefully during
treatment so that silent neuropathy can be detected]
4- Treatment → as reversal reaction
N.B all types of leprosy are seen in childhood usually > 5 years. Reactions in children are treated
with prednisolone 0.5 mg/kg/day

16
Treatment
1- Education of the patient → the key to successful management
- Low infectivity of the disease
- Importance of treatment adherence and/ or compliance
- Warnings about reactions
- Care of anaesthetic hands and feet
- Support with social issues
2- Rifampicin
- Effect → potent bactericidal for M.leprae (4 days after a single 600 mg
dose, bacilli are no longer viable)
- Action → inhibit DNA- dependent RNA polymerase → interfering with
bacterial RNA synthesis
- Side effects → hepatotoxicity and resistance to M.leprae so, should be
given in combination with other drugs
3- Dapsone
- Structure → DDS; 4,4 diaminodiphenylsulphone
- Mode of action → blocking folic acid synthesis
- Effect → weak bactericidal but oral absorption is good with long half
life averaging 28 h
- Side effects
 Haemolytic anemia esp. patients with G6PD deficiency
 DDS syndrome → may start after 6 weeks after treatment and
manifests as exfoliative dermatitis associated with
lymphadenopathy, HSM, fever and hepatitis
 Rarely, agranulocytosis, hepatitis and cholestatic jaundice may
occur
4- Clofazimine
- Action
 It is a dye that has a weakly bactericidal action
 Also has anti-inflammatory effect and can prevent ENL

17
 - Side effects
 Skin discoloration → ranging from red to purple black, the
pigmentation usually clears up within 6-12 months of stopping
the drug, although traces of discoloration may remain for up to 4
years
 Characteristic icthyosis on the shins and forearms
 GIT effects ranging from mild cramps to diarrhea and weight loss
(crystal deposition in the wall of the small intestine)
5- Multidrug therapy
- Advantages
 Relapse rates are low (patients with high initial bacterial loads are
at greater risk of relapse -8 per 100 person-years)
 No drug resistance
 Toxicity is limited
 Duration of treatment is greatly shortened
 Rapid response
- All drugs should be given in full doses from the beginning and without
interruption even during the reactions if it occur
- Modified multidrug therapy regimens recommended by WHO

Monthly supervised and Daily self administered Duration

Type of leprosy

Paucibacillary (PB) Rifampicin 600 mg Dapsone 100 mg 6 months

Multibacillary (MB) Rifampicin 600 mg Clofazimine 50 mg 24 months*
Clofazimine 300 mg Dapsone 100 mg & until skin
smear becomes
-ve

Children
PB → Rifampicin 450 mg monthly and dapsone 50 mg daily
MB → Rifampicin 450 mg and clofazimine 150 mg monthly, clofazimine 50 mg
alternate days and dapsone 50 mg daily
2nd line drugs [if adverse effects or drug interactions]
Ofloxacin → 400 mg
18
Minocycline → 100 mg
WHO now recommend 12 months only for multbacillay type
Although there were no controlled trial data to guide this decision

- WHO classification for field use when slit skin smears are not available
Paucibacillary [TL & near tuberculoid borderline cases = -ve skin smears or
with few bacilli] up to 5 skin lesions
Multibacillary [LL & near lepromatous borderline cases] ≥ 6 skin lesions

- Careful follow up for 5 years after stopping the treatment is essential. If

relapse occurs give another course
- In case of indeterminate leprosy
 If the bacilli are found in the skin smears → treat as in
multibacillary leprosy
 If no bacilli are found → treat as paucibacillary leprosy
5- Treatment of type 1 (reversal) reactions ®
6- Treatment of erythema nodosum leprosum reaction ®
7- Treatment of neuritis ®
8- General care of hands and feet
- Self care training
 Inspect for injury
 Understand why injuries happen
 Soak feet and oil
 Remove callus
 Exercise hands and feet
 Treat injuries promptly
- Hands
 Problems with heat/pressure/sharp objects
- Feet
 Planter ulcers occur at pressure sites
 Either walk less or use protective shoe insoles
- Footwear
 Check shoe fittings
 Provide insoles
 Arch supports, metatarsal pads
 Orthopedic footwear
- Management of planter ulcers
 Clean wound
 Bed rest, walking plaster
19
  Check footwear
 Find out why it happened
9- Reconstructive surgery
- Tarsorrhaphy or temporalis muscle transfer → for lagophthalmos
- Appropriate tendon transfers → can reduce the effects of ulnar and
median nerve paralysis and improves drop foot and claw toes
- Cosmetic surgery esp eyebrow replacement, nasal reconstruction and
reduction of gynaecomastia is important in rehabilitation of severely
deformed patients
10- Treatment during pregnancy and lactation
- Rifampicin, dapsone and clofazimine are safe during pregnancy, but
ideally pregnancies should be planned for when leprosy is well
controlled
- Women may breast feed while on multidrug therapy but should be
warned that low levels of clofazimine are excreted in the breast milk and
may cause some skin discoloration in the infant
11- Prophylaxis to contacts
- BCG vaccination → confer variable protection (cross reactivity)
- Dapsone 50 mg/day for one year or Acedapsone 225 mg IM every 3
months for 3 years

21
Cerebral amoebiasis

[® The same pathogenesis, investigations, history of C/P of amoebiasis with stress on the following]

Etiology
1- Extraintestinal amoebiasis [E. histolytica]
- Amoebic brain abscess
- Amoebic meningitis
2- Pathogenic free living amoeba
- Acute primary amoebic meningoencephalitis [Naeglaria fowleri]
- Chronic primary amoebic meningoencephalitis [Acanthamoeba species]
Naeglaria fowleri
Pathogenesis
1- Infective stage → trophozoite (swimming) , cyst (air-borne)
2- Source → fresh water lakes and ponds
3- Mode of transmission
- While swimming in contaminated water, trophozoite invades the nasal
mucosa and reach cranial cavity (the most common way)
- Sniffing contaminated water
- Inhalation of contaminated air
4- Pathology
- Amoebae are the only forms detectable in brain tissue (flagellates and
cysts are never found in tissues or CSF)
- Diffuse meningoencephalitis with haemorrhagic inflammation and
necrosis of brain tissue
Clinical features [acute 1ry amoebic meningoencephalitis]
1- Acute fulminant rapidly fatal disease affects mostly children and young adults
2- Fever, headache, vomiting
3- Sore throat
4- Disturbance in the sense of smell or taste may occur
21
 5- Signs of meningitis ® neck stiffness, convulsions
6- Coma
7- Death in 4-6 days
Investigations
1- History of swimming within the preceding days is suggestive
2- LP
- Microscopic examination reveals amoeba form
- Culture on suitable medium
- Suspension in fresh water incites transformation into flagellate forms
that confirm the diagnosis
- CSF and under tension
3- Film and culture on non-nutrient agar enriched with E.coli and intracerebral
inoculation in mice
Treatment
1- No complete satisfactory treatment
2- IV amphotericin B → 1-1.5 mg/kg/day for 3 days followed by 1 mg/kg daily for
6 days
3- Amphotericin B can additionally be given intrathecally

Acanthamoeba species
1- Mode of infection
- GAE → 1ry infection occurs in the lower respiratory tract, ulcerated
skin or ulcerated mucosa → hematogenous spread carries the parasite to
the CNS and possibly other organs as kidney, uterus and pancreas → in
AIDS disseminated infection can develop
- Acanthamoeba keratitis → amoeba introduced through corneal trauma,
exposure to contaminated water and wearing of contaminated contact
lenses
2- Pathology
- Focal granulomatous lesions in the brain, skin and internal organs
22
 - Single or multiple focal space occupying lesions are produced
3- Clinical features
- Chronic granulomatous amoebic encephalitis
 Lasting from weeks to months or years
 Same C/P of Naegleria
- Keratitis, corneal ulcer and endophthalmitis (AIDS) → severe ocular
pain and blindness
- Granulomatous lesions of the skin and internal organs
4- Investigations
- CSF examination reveals the parasite
- Identification of trophozoites and cysts in corneal scraping directly and
after culture
5- Treatment
- No satisfactory treatment
- Granulomatous encephalitis
 Excision of the focal lesion and treatment with ketoconazole
 Penicillin and chloramphenicol
- Keratitis
 Oral itraconazole + topical miconazole
 Corneal transplant

Amoebic meningitis ®
Amoebic brain abscess
Features
1- Fever , headache
2- Focal manifestations e.g. hemiparesis, aphasia, epilepsy
3- ↑ ICT
4- Investigations
- CT, MRI
- LP is dangerous and unhelpful

23
Treatment
1- Parenteral metronidazole 500 mg IV/8 hrs + gentamicin + 3rd generation
cephalosporins or ampicillin
2- Dehydrating measures for cerebral edema
3- Surgical decompression may be required for brain abscess
4- Treatment of invasive amoebiasis ®

Intracorpuscular infections

Organisms found inside RBCs

1- Malaria
2- Babesia

Babesiosis

Pathogenesis
1- Infective stage → sporozoites
2- Definitive host
- B. divergens → in cattle
- B. microti → in rodents
3- Mode of infection
- Bite of hard ticks
- Blood transfusion
4- Parasites invade RBCs where they multiply by budding → the cells rupture
and the released organisms infect other RBCs
Clinical features
1- Asymptomatic or mild and in most cases it is self limited
2- Mild form characterized by
- Fever, chills, headache, myalgia and backache.
- Fever not show periodicity as in malaria

24
 - Mild to moderate hemolytic anemia → jaundice
3- More severe form [malaria like picture]
- Rapidly progressive
- Fever, hemolytic anemia, jaundice, HSM and renal failure may also
develop
4- In splenectomized patients the course is more fulminant (opportunistic
parasite)
Investigations
1- Blood film examination
- Parasites appear inside RBCs as ring stage of P.falciparum (multiple
small rings in RBCs)
- Differentiated from P.faciparum by absence of pigment and gametocyte
stage
2- Serological
- IHA, IFA
- Useful esp. in presence of low parasitaemia
3- PCR → detect babesia DNA accurately
Treatment
1- Combination of Clindamycin 600 mg 3 times daily orally + Quinin 650 mg 3
times daily orally for 7 days
2- Pentamidine → 3 mg/kg/day IM for 15 days
3- Exchange blood transfusion → in severe cases reduces parasitemia and anemia

25
Corona virus

Pathogenesis
1- The virus
- Enveloped RNA viruses with surface projections look like a crown
- 3 major strains
 Human corona viruses (HCoV) 229E and OC43
 Severe acute respiratory syndrome corona virus (SARS- CoV)
2- Mode of transmission
- HCoV → by aerosols
- SARS-CoV → by close contact, droplets and possibly faecal-oral route
3- Distribution
- HCoV → worldwide and infection occur throughout the year affecting
all age groups
- SARS-CoV → an epidemic started in 2002 in southern China and
spread to other parts of the world → the epidemic ended in 2003
affecting 8500 patients (95% in Asia) with a mortality rate of 9.5%
Clinical features
1- I.P.
- 2-5 days for HCoV
- 2-10 days for SARS-CoV
2- Common cold
- Caused by HCoV and responsible for 25% of cases of colds
3- Severe acute respiratory syndrome [Atypical pneumonia caused by SARS-
CoV]
- Fever, malaise, headache, cough, dyspnea, hypoxemia, pneumonia and
diarrhea
- Acute respiratory failure and death occurred in 10% of cases

26
Investigations
1- Growth in tissue culture
2- Electron microscopy
3- Serology → IFA, EIA and immunoblot
4- PCR for nucleic acid detection
5- Chest X ray → interstitial "ground glass" infiltrates
Treatment → symptomatic
Prevention → no specific vaccine

AIDS

Definition → AIDS is the end stage manifestation of a long standing infection with a
retrovirus HIV
Types of the virus
1- HIV 1 → predominant in Europe and America (more aggressive)
2- HIV 2 → predominant in Africa (carrier rate about 30%)
Risk groups
1- Homosexuals and heterosexuals
2- IV drug abusers
3- Hemophilics
4- Blood transfusion recipients
Mode of transmission
1- Sexual esp. homosexuals
2- Blood born
- IV drug abuse
- Blood transfusion
- Organ donation
- Accidental

27
 3- Vertical transmission from mother to infant during delivery. Also by breast
feeding
4- Dental procedures
Pathogenesis [immunological abnormalities]
1- T4 (T-helper cells) lymphocytes decreased in number with abnormal function
(the virus has a characteristic cytopathic tropism for lymphocytes)
2- Abnormal function of monocytes and macrophage
3- Abnormal function of B lymphocytes
Incubation period
1- About 4-6 weeks up to years after infection
2- After 4-6 weeks → the patient may present as group A
3- After months or years → the patient may present as group B or C
Clinical presentation, classification and sequelae
1- Group A
- Asymptomatic carrier or
- IMN like + Persistent generalized lymphadenopathy (enlarged lymph
nodes > 1 cm in diameter in 2 anatomically distinct sites for > 3 months)
2- Group B
- AIDS related complex (constitutional symptoms + minor opportunistic
infections)
 Fever
 Diarrhea
 Weight loss
 Oral candida
 Herpes zoster in more than one dermatome
 LN enlargement
 Peripheral neuropathy
 ITP

28
 3- Group C [defining features of AIDS]
- HIV associated infections (major opportunistic)
 Disseminated CMV, CMV retinitis
 Disseminated candidiasis, herpes virus
 Mycobacterium avium, tuberculosis
 Extraintestinal strongyloidiasis
 Pneumocystis carinii (commonest opportunistic infection in
AIDS)
 Toxoplasmosis of brain
- HIV associated malignancy
 Kaposi's sarcoma
 Lymphoma
 Non Hodgkin's lymphoma
 Primary brain lymphoma
Manifestations and effects on different systems
1- Skin
- Kaposi's sarcoma
 Diagnoses 25% of AIDS cases
 Violaceous lesions as bruises which gradually darken
 Initially flat but later most of the lesions become raised firm nodules
 Lesions develop at several sites simultaneously, initially, they are not painful
or itchy and they are widely distributed
- Mucocutaneous herpes simplex persisting for at least one month
- Fungal infections
- Herpes zoster
- Seborrhea
- Secondary syphilis
- Folliculitis, cellulitis, impetigo
- Drug eruption
- Non hodgkin's lymphoma
2- GIT
- Mouth
 Oral candidiasis
 Angular stomatitis
 Aphthous ulcers

29
  Kaposi's sarcoma → may occur on the hard palate, soft palate, gingival and
buccal mucosa. Color is red blue or purple and may be flat or raised, solitary
or multiple
 Hairy leukoplakia → specific for HIV. It is asymptomatic whitish lesion
found on the lateral margin of the tongue. Its surface may be smooth,
corrugated or markedly folded
 Herpes simplex virus → recurrent painful ulcerations mostly on the palate
 Human papilloma virus → multiple and recurrent oral papillomas and
condylomatas
 Lymphoma → may present as firm painless swelling in the mouth which
may ulcerate (may be the 1st presentation)
- Esophagus
 Infectious esophagitis → candida, CMV, herpes (dysphagia, odynophagia)
 Kaposi's sarcoma
- Stomach
 Kaposi's sarcoma
 CMV
 Bleeding due to associated hepatitis B,C and ethanol intake
 Hypochlorhydria → which lead to reduced absorption of acid soluble drugs
as ketoconazole
- Small bowel
 Chronic diarrhea → the commonest manifestation (50-90% of cases) →
weight loss, severe malnutrition, abdominal pain and may be bowel
perforation and bleeding per rectum. Causes include: 1- cryptosoridum
(50%) 2- isospora belli (15%) 3- giardia 4- CMV 5- HSV 6- salmonella 7-
shigella flexneri 8- campylobacter 9- mycobacterium avium 10- kaposi's
sarcoma 11- strongyloids
 Malabsorption
- Colorectal
 CMV colitis
 Tenesmus
- Hepatobiliary (no direct effect on the liver but ↑ susceptibility)
 Viral hepatitis → A,B,C,D, and rarely CMV, EBV, HSV, VSV
 Disseminated mycobacterium avium complex infection
 Peliosis hepatis
 Disseminated fungal and protozoal infections (infiltrate the liver)
 Lymphoma
 Kaposi's sarcoma
 HCC
 NAFLD
 Antiretroviral induced hepatotoxicity
 AIDS cholangiopathy
 Acalculous cholecystitis

31
3- Respiratory
- Pneumocystis carinii pneumonia
 The presenting feature in 50% of cases
 Fever, malaise, fatigue, non productive cough, dyspnea and cyanosis.
Auscultation often normal
 X-ray shows bilateral diffuse shadows
 Diagnosis by bronchoscopy with biopsy or lavage and examination using
silver staining technique
- Bacterial pneumonia
 10% of cases
 Cause → streptococcus, staphylococcus and H.influenzae
 No typical radiographic features
- Pulmonary lesions may be caused by
 Kaposi's sarcoma
 Lymphoma
 Cryptococcus, aspergillus and candida
 M.avium and tuberculosis
 CMV
Main features of tuberculosis in HIV
Most cases due to reactivation
Extrapulmonary TB is common
TB may accelerate HIV disease
Tuberculin test is –ve (anergy)
6-9 months therapy is recommended but INH prophylaxis should continue
for life to prevent relapse

4- Nervous system (30% of cases)

- Encephalopathy
 Caused by direct HIV infection of the brain
 Subcortical dementia → cognitive and behavioral changes as mental
slowness and apathy. Depressive symptoms and organic psychosis with
hallucinations may occur. Hyperreflexia in 50% of cases
 The condition may progress to severe global dementia
 CT scan shows diffuse cerebral atrophy in 75% of cases
- Myelopathy and acute transverse myelitis
 Caused by vacuolation in the spinal white matter
 Spastic paraparesis which may be asymmetrical associated with bladder
dysfunction and signs of sensory ataxia
- Neuropathy mostly peripheral, sensory neuropathy causing painful paraethesia in the
lower limbs
- Inflammatory demyelinating polyneuropathies mimicking Guillain Barre syndrome
and mononeuropathies are recorded
- Encephalitis and retinitis → HIV, HSV, CMV, HZV and atypical mycobacteria
31
 - Meningitis → cryptococcal and TB meningitis
- Space occupying lesions → 1/3 of cases developed cerebral toxoplasmosis which
causes multiple necrotic abscesses
- Primary lymphoma of CNS → in 5% of cases
5- Blood
- ITP, lymphoma
- Anemia
 BM infiltration by lymphoma or TB
 Blood loss from kaposi's sarcoma
 ↓ B12 due to malabsorption on top of intestinal infections
6- Renal
- HIV nephropathy
- Drug nephropathy
7- Heart → myocarditis, pericardial effusion
8- Endocrine → CMV adrenalitis
9- Psychiatric → anger, guilt, anxiety with panic attacks and depression
Diagnosis
1- Clinical suspicion [at least 2 major + 1 minor manifestation]
- Major manifestations
 Unexplained fever > 1 month
 Unexplained diarrhea > 1 month
 Unexplained weight loss > 10% of previous weight
- Minor manifestations
 Presence of maculopapular rash
 Persistent Oral candidiasis or thrush
 Herpes zoster or shingles
 Aggressive uncontrolled herpes simplex
 Unexplained cough > 1 month
 Enlarged lymph nodes in more than one extra inguinal site
2- Laboratory diagnosis
- Positive HIV antibodies → by ELISA (has some false positive results)
- Positive HIV antibodies → by Western blot (confirmatory for the
diagnosis)
- PCR → very specific for DNA replication
- Lymphopenia esp. T cell lymphopenia
32
 - ↓ CD4 count < 400/mm3. Patients with counts < 200 at a very high risk
- T4 (helper ↓) : T8 (suppressor ↑) ratio < 1 (severely reduced)
- Detection of viral antigens [p24 by ELISA]
 The only marker in the window period early in infection when
antibodies are not detected
 Donated blood should be tested for this antigen to ensure its
safety
- Anemia, leucopenia and thrombocytopenia
- ↑ serum immunoglobulin level (abnormal function of B lymphocytes)
- ↑ ESR
- Cutaneous anergy
Treatment [no specific drug or vaccine until now]
1- HAART [highly active antiretroviral therapy]
- Action
 Drugs used act by stopping virus cell fusion, intracellular
synthesis by inhibiting the RT enzyme or by inhibiting the
protease enzyme
 These drugs inhibit production of infectious viral particles but not
affect the proviral DNA
- Reverse transcriptase inhibitors
 Nucleoside/nucleotide RT inhibitors
© Zidovudine (AZT) ↓
© Didanosine (ddI) → as AZT but less toxic
© Lamivudine (3TC) and stavudine (d4T) → used in cases
intolerant or resistant to AZT or ddI
© Emtricitabine (FTC)
© Abacavir (ABC)
© Tenofovir (TDF) → the only nucleotide analogue RT inhibitor
 Non nucleoside RT inhibitors e.g. Nevirapine (NVP), Efavirenz
(EFV)

33
 - Boosted Protease inhibitors
 Lopinavir/ ritonavir
 They are inhibitors of the protease encoded by HIV thus
inhibiting cleavage of precursor polypeptides required for viral
replication
 The main side effect → deposition of fat in the back of the neck
"buffalo hump" and in other parts of the body
- Fusion inhibitors
 Enfuvirtide [injection]→ it is a synthetic peptide that binds to
gp41 on the viral envelope thereby blocking the entry of HIV into
the cell [inhibit fusion of the viral envelope with the cell
membrane]
© 1st line regimen
2 NRTIs + 1 NNRTI [for example → AZT or d4T (or TDF or ABC) plus
3CT or FTC plus EFV or NVP
© 2nd line regimen
2 NRTIs not used in the first line + a boosted protease inhibitor [for
example → ddI or TDF plus ABC plus lopinavir/ritonavir

- Effect of this combination

 ↓ viral load to undetectable levels
 ↑ CD4 count and ↑ CD8 activity
 Prolongs and improves the quality of life
 Does not cure the latent infection
 Help in delaying the emergence of resistant variants
2- Antivirals
- Zidovudine (AZT)
 Effects → improves the survival, ↑ CD4 count, ↓ opportunistic
infections, improves general well being and increases the weight
of the patients
34
  Structure → nucleoside analogue reverse transcriptase inhibitor
(NRTI)
 Dose → 250 mg orally every 6 hours daily for 6 weeks. To
reduce the dose interferon may be added
 Side effects → nausea, headache and insomnia. Severe
macrocytic anemia and agranulocytopenia necessitating drug
stoppage and blood transfusion
- Immune therapy
 Interferons, interleukins, Isoprinosine and lymphocyte transfusion
- Ganciclovir
 The drug of choice for CMV infection
 Dose → 5 mg/kg IV every 12 hours for 2 weeks
- Acyclovir
 For herpes simplex virus infection. Also HZV
 Topically, orally or IV [200 mg orally every 4 hours per day]
- Desciclovir (acyclovir analogue)
 For hairy leukoplakia
3- Antiprotozoals
- Cryptosporidiosis
 Spiramycin 2-3 gm orally daily
 Hydration, correction of electrolyte imbalance and proper caloric
intake
- Pneumocystis carinii
 Co-trimoxazole 20 mg/kg daily IV for 2 weeks then given orally
[side effects → fever, nausea, rash and BM suppression]
 Pentamidine mesylate 25 mg/kg daily slow IV [hypoglycemia and
hypotension may occur]. May be used by inhalation
- Isospora belli → co-trimoxazole and metronidazole
- Toxoplasma → fansidar (pyrimethamine sulphadoxine) 25 mg/kg daily

35
4- Antigungals
- Cryptococcosis
 IV amphotericin B + flucytosine followed by fluconazole
 Side effects → nausea, rash, renal impairment and BM
suppression [response rate 60%]
- Candida
 Ketoconazole 200 mg 3 times daily orally
 Local agents as nystatin
 IV amphotericin B in disseminated disease
5- Antituberculous
- Standard quadruple therapy → INH+ pyrazinamide + rifampicin +
ethambutol
6- Anticampylobacter
- Erythromycin 1 gm orally every 6 hrs daily
7- Lymphoma → chemotherapy + irradiation
8- Kaposi's sarcoma
- Radiation therapy and laser surgery
- Immunomodulation as interferon
- Cytotoxic chemotherapy with vinblastine and/or pentamidine
9- Prevention
- Post exposure prophylaxis
 Combination of zidovudine + lamivudine given within 72 hrs of
accidental infection for 4-6 weeks
 Recommended following needle stick injuries or other parenteral
exposure with known HIV infected material
 Reduce but not remove the risk of infection
- Screening
- Counseling
- Condoms
- Glutaraldehyde 2% for 1 hr is effective for disinfection of instruments
used for patients
- Society education
36
 Peptic ulcer disease

Etiology and risk factors

1- H.pylori infection ®
2- NSAIDs → ↓ gastric and duodenal PG [PG → stimulate bicarbonate and mucus
secretion from the gastric mucosa. Also increase microvasculature of the
mucosa]
3- Smoking → ↓ ulcer healing and ↑ the incidence of recurrence
4- Reflux → ulcers at lower esophagus
5- Zollinger - Ellison syndrome
6- More common in men than women
7- More common with blood group O
8- Familial esp. in duodenal ulcer
9- Cirrhosis → due to ↓ destruction of gastrin and histamine by liver and ↓
mucosal viability due to congestive gastropathy
10- Uremia
Symptoms
1- Epigastric pain
- Character → burning, stabbing or dull ache
- Site : patient points to the epigastrium
 The patient can indicate its site with 2 or 3 fingers (the pointing
sign)
 Back pain suggests penetrating ulcer
- Relation to meals (variable)
 Duodenal ulcer: worse when the patient is hungry and at night
 Gastric ulcer : it occurs 0.5 – 1 hr after meals
- Night pain → pain wakes the patient from sleep suggests DU
- Pain relief
 Duodenal ulcer : food, antacids and vomiting
 Gastric ulcer : fasting, antacids and vomiting
37
 2- Nausea → may accompany the pain
3- Vomiting →infrequent but often relieves the pain
4- Appetite (variable)
- Duodenal ulcer
 It increases in most cases
 The patient may identify the pain as hunger pain and obtains
relief by eating, weight gain may occur
- Gastric ulcer
 Patient may suffers from sitophobia for fear of pain, weight loss
may occur
5- Heart burn → it occurs due to acid regurgitation. Water brash also may occur
6- Episodic pain (periodicity)
- Esp. in duodenal ulcer
- The pain occurs in episodes lasting 2-3 weeks at a time, 3 or 4 times in a
year and between episodes the patient feels well
7- Manifestations of complications [the presenting symptoms in some patients]
Signs
1- May be normal
2- Tender epigastrium
3- Signs of anemia
4- Signs of peritonitis with perforation
Complications
1- Bleeding → hematemesis, melena or anemia
2- Perforation
- Common in duodenal ulcer
- Generalized peritonitis or subphrenic abscess
- Plain X ray showing pneumoperitoneum
3- Fibrosis and obstruction
- Gastric outlet obstruction
- Hour glass stomach

38
 4- Penetration
- Pain usually sudden and radiates to the back with rise of serum amylase
5- Malignancy → in gastric ulcers [malignant ulcer mostly malignant from start]
Investigations
1- Upper endoscopy
- Exclude GERD and malignancy
- Differentiate between benign and malignant gastric ulcers [all gastric
ulcers should be biopsied]
2- Barium meal :less commonly used
- Gastric ulcer
 Ulcer niche on the lesser curvature with serial films
 Notch on the greater curvature opposite the niche
- Duodenal ulcer
 Deformity of the duodenal cap with serial films
3- Investigations for H.pylori ® see before
Differential diagnosis
1- Cholecystitis
2- Pancreatitis
3- GERD
4- Gastric carcinoma
5- Inferior wall myocardial ischemia or infarction
Treatment
1- Dietary and life style changes → see GERD ® +
- Avoid NSAIDs or use selective COX2 inhibitors
- Avoid excessive milk intake as it may increase acidity due to its calcium
content
- Stop smoking
- Avoid irritant foods
- Encourage soft bland diet. It is better to be small and frequent

39
2- Medical treatment
- Aims → relief pain, induce ulcer healing and prevent complications and
recurrence
- H2 blockers
 Duration is 4-6 weeks to ensure ulcer healing
 They inhibit histamine receptors – inhibit both basal and
stimulated gastric secretion accelerating healing
 Ranitidine 300 mg/d
 Famotidine 20-40 mg/d
 Cimetidine 200 mg 4 times /day but may cause impotence and
gynaecomastia
- Proton pump inhibitors
 Duration is 6 weeks for duodenal ulcer and 8 weeks for gastric
ulcer
 The final phase of H+ secretion by parietal cells is helped by an
enzyme called (H+, K+-ATPase) which serves as a proton pump
exchanging potassium for hydrogen. PPIs are specific to inhibit
this enzyme so decreasing HCL secretion. It leads to
hypergastrinaemia
 Omeprazole 20 - 40 mg/d
 Pantoprazole 40 mg/d
 Lanzoprazole 30 mg/d
- Sucralfate
 It is a complex salt of sucrose sulphate and aluminum hydroxide
acting as a cytoprotective and coating agent
 It inhibits H diffusion to the base of the ulcer. Stimulates mucous
and bicarbonate secretion. Enhances mucosal defense and repair.
Increases endogenous tissue PG so help healing
 Dose → 1 gm 1 hr before each meal
 It is good for biliary gastritis

41
  Contraindications → chronic renal failure to prevent aluminum
induced neurotoxicity
- Misoprostol (PGE1 analogue)
 It stimulates mucosal blood flow. Increases mucosal defense and
repair. Increases mucous and bicarbonate secretion
 It is mainly used as a cytoprotective agent in prevention of
NSAIDs associated gastric ulcers
 Dose → 200 µg 2-4 times/day (Misotec)
 Side effects → diarrhea and abdominal pain
- Antacids
 Aim to increase PH > 4 so inhibits pepsin activity so relieves
pain, also they accelerate healing
 Mg hydroxide → reacts quickly but causes diarrhea
 Ca carbonate → reacts quickly to form CaCL which is
absorbable. It causes constipation and when combined with milk
→ milk alkali syndrome with hypercalcemia and
hyperphosphatemia
- Eradication oh H.pylori ® see before
3- Surgical treatment
- Indications
 Failure of medical treatment
 Recurrent uncontrollable bleeding
 Perforation or penetration
 Pyloric obstruction
 Possible malignancy
- Partial gastrectomy
 Billroth 1 → the lower part of the stomach is removed and
stomach remnant is connected to duodenum [reduction of parietal
cell mass]

41
  Billroth 11 → the remnant of the stomach is connected to the first
loop of jejunum [polyagastrectomy]
- High selective vagotomy
 Elimination of the cephalic phase of acid secretion by division of
the vagus
 Can be either a) truncal or b) highly selective with preservation of
the antral and pyloric innervations
- Complications → see later
4- Treatment of complications
- Perforation or penetration
 NGT suction
 IV fluids
 Antibiotics and analgesics
 Surgery to repair the perforation with omental patch and drain the
abdomen
- Bleeding
 I.V. PPIs bolus of 80 mg then drip at 80 mg/hr for 72 hr
© Has shown to accelerate resolution of bleeding and decrease need for
therapy during OGD
© The reduction of intraluminal acid may be effective in two ways. First, the
direct, harmful effects of acid and pepsin on the bleeding lesion are
diminished. Second, a less acid environment allows platelets to aggregate
and thus promotes clotting
 Blood transfusion if indicated

42
 Bleeding duodenal ulcer
- The bleeding artery is the gastroduodenal artery
- Mathods of stopping bleeding by endoscopy:
 Adrenaline 1:10000
 Cautery
 Argon plasma coagulation
 Hemoclip
 Hemostatic spry

- Combining injection therapy with electrocoagulation may have added benefits and is
currently being widely used
- The bleeding stops and the patient stays 1-2 days NPO, given PPIs for 6 weeks plus
eradication of H.pylori
- The patient can eat or drink after 1-2 days
Bleeding gastric ulcer
- The same modalities as duodenal ulcer but PPIs given for 8 weeks plus eradication
of H. pylori
- Peptic ulcer could be malignant, so biopsy recommended

- Pyloric obstruction
 Fluid and electrolyte replacement with nasogastric suction via a NGT
 Surgery
Complications of surgery
1- Early dumping syndrome (postprandial vasomotor symptoms)
- Nausea, distention associated with sweating, faintness, palpitation and
flushing that occur following gastrectomy
- It occurs particularly after sweet foods (after 30 minutes)
- It is due to rapid gastric emptying of food into jejunum, which is
followed by rapid influx of fluid to dilute the osmotic load, also release
of serotonin and VIP is incriminated
- Treated by symptomatic treatment and ingestion of small meals with
avoidance of fluids at meal time.

43
 - Surgery may be indicated e.g. Billroth 11 → Billroth 1
2- Late dumping syndrome
- Hypoglycemia in the 2nd hour after eating
- Due to rapid absorption of glucose causing hyperglycemia →
hyperinsulinemia
3- Chronic diarrhea
- Occur after vagotomy due to motility disorders
- May occur due to bacterial overgrowth in the blind loop of a
polyagastrectomy, antibiotics is helpful
- Treated by loperamide
- Cholestyramine helps in cases of increased excretion of bile acids
4- Vomiting
- Due to trapping of food as a result of altered anatomy
5- Nutritional complications (maldigestion and malabsorption)
- Iron ↓ anemia
- B12 ↓ with long term gastritis with ↓ IF
- Osteomalacia, protein malnutrition
6- Stagnant loop syndrome → see malabsorption
7- Bezoar
- Plant material present in the stomach in cases of gastroparesis or after
gastric surgery
- Pain, nausea and vomiting. May be palpable epigastric mass
- Diagnosed by plain X ray and endoscopy
- Treatment by disruption at endoscopy or by enzyme ingestion
8- Alkaline or bile acid gastritis (Biliary gastritis)
- Due to excessive reflux of bile and pancreatic and intestinal secretions
into the stomach
- It may result from gastric resection or bypassing the pylorus
- Unresponsive to antacids
- Sucralfate is better

44
 - Surgical diversion of pancreaticobiliary secretions away from gastric
remnant with a Roux-en-Y gastrojejunostomy
9- Recurrent ulcer after surgery
- Eradication of H.pylori is important
- Consider Zollinger-Ellison syndrome

Protein losing enteropathy

Definition → it is an increased protein loss across an abnormal gastrointestinal

mucosa causing hypoalbuminemia
Causes
1- Gastric carcinoma
2- Atrophic gastritis
3- Intestinal lymphangiectasia
4- Whipple's disease
5- Celiac and tropical sprue
6- Inflammatory bowel disease
7- TB enteritis
8- Cancer colon
9- Congestive heart failure
10- Constrictive pericarditis
11- Esophageal carcinoma
12- Scleroderma
13- Parasitic infections

45
 Diverticular disease

Definition
1- Generally refers to diverticulosis of the colon and its complications
2- However, diverticula can occur throughout the GIT
- In esophagus → may cause dysphagia
- In stomach → usually asymptomatic
- In the small intestine → predispose to bacterial overgrowth and
malabsorption

Diverticulosis

Definition
1- The presence of one or more diverticula (outpocketing from the bowel wall)
Pathogenesis
1- True diverticula
- Found occasionally in the colon
- In which the walls contain all layers of the bowel
2- Pseudodiverticula
- The most common
- These are herniations of mucosa and submucosa through the muscularis
propria at the sites of penetration of the nutrient arteries
3- Etiology
- Increased pressure within the lumen of the bowel which over time
causes the herniations
4- Site
- Most diverticula occur in the sigmoid and descending colon due to high
intraluminal pressure
- Also may found more proximally

46
 5- Risk factors
- Incidence increased with age
- More frequent in populations in which dietary fiber has been replaced
by refined CHO
- Long standing constipation
Clinical features
1- Old age with long standing constipation
2- Asymptomatic in most patients
3- Chronic or recurrent left lower abdominal pain
4- May be flatulence and dyspepsia
5- Examination → may reveal tenderness and a firm feces filled sigmoid colon
6- PR → the stool may be firm and tests for occult blood are usually negative
7- May be alternating constipation and diarrhea confuse the condition with irritable
bowel syndrome
8- Complications
- Diverticulitis
- Bleeding per rectum
- Diverticular bleeding and acute diverticulitis rarely coexist. However, it
is likely that some degree of peridiverticular inflammation is present in
patients who bleed from diverticula
Investigations
1- CT scan of the abdomen and pelvis → showing the diverticula
2- Barium enema x ray examination
- Shows one or numerous barium filled pockets protruding outside the
bowel lumen
- The distortion of the normal mucosal architecture by diverticulosis
sometimes makes it difficult to exclude carcinoma or polyp by barium
enema examination
3- Sigmoidoscopy or colonoscopy
4- Urinalysis and CBC

47
Differential diagnosis
1- Irritable bowel syndrome
2- Frank diverticulitis
3- Cancer colon
4- Crohn's disease or proctocolitis
5- Urologic and gynecologic disorders
Treatment [uncomplicated symptomatic = as IBS]
1- High fiber diet
- Alleviate the discomfort of diverticular disease
- Can be added in the form of unprocessed bran and other hydrophilic
bulk laxatives such as Metamucil
2- Antispasmodic anticholinergic drugs
- As dicyclomine HCL for crampy abdominal pain
3- In constipated patients
- Lubiprostone may be preferred to induce softer stools
- Cathartic laxatives should be avoided
4- Treatment of diverticular bleeding
- Stop spontaneously in 75% of cases
- Therapeutic colonoscopy
 Placement of metallic hemoclips
 Thermal coagulation (heater probe, argon plasma coagulation,
bipolar or multipolar coagulation)
 Injection of vasoconstrictors and sclerosants
5- Treatment of diverticulitis → see below

48
Diverticulitis

Etiology
1- Diverticulitis occur when feces obstruct the neck of the diverticulum →
stagnation → bacterial multiplication → inflammation
Clinical features
1- Symptoms evolve over several hours or days but the patient may be present with
an acute abdomen
2- Fever and tachycardia
3- Acute left lower abdominal pain
4- Tender abdomen and may be rebound tenderness
5- Mass in left iliac fossa → divericular abscess or inflammatory phlegmon
6- Bowel sounds
- Active → partial or complete obstruction
- Hypoactive or absent → peritonitis
7- PR → may localize the abscess or inflammatory mass
8- If chronic diverticulitis occurs → chronic inflammatory changes which may
resemble IBS or Crohn's disease
9- Complications
- Divericular abscess
- Perforation and peritonitis
- Fistula with urinary bladder (colovesical) with dysuria and pneumaturia
Differential diagnosis
1- Infectious C. difficile
2- Ischemic colitis
3- IBD
4- Cancer colon
5- Gynecologic disorders as ruptured ovarian cyst
6- Urologic disorders as renal colic

49
Investigations
1- Acute lower abdominal pain + fever + elevated TLC in a person with
demonstrated diverticula are sufficient for diagnosis of diverticulitis
2- CBC
- ↑ TLC with shift to the left
- Hb and Ht may reflect hemoconcentration
3- Urinalysis
- May show WBCs and RBCs
- In colovesical fistula → the urine contains large numbers of pus cells
and bacteria and possibly feces
4- Plain X ray abdomen (supine and erect)
- Air fluid levels → ileus or obstruction
- Free air in the abdomen → perforated diverticulum
5- CT scan and U/S of the abdomen and pelvis
- Identify diverticular abscess or inflammatory mass
- Exclude other DD as ovarian cyst
6- Sigmoidoscopy, colonoscopy and barium enema x ray examination
- Endoscopy may be performed cautiously if perforation is not suspected.
However, it is best to delay until symptoms have subsided
- Diagnosis by barium enema requires evidence of perforation of a
colonic diverticulum by demonstrating either a fistulous tract or an
abscess cavity [ unequivocal findings and not necessary to make
diagnosis]
Treatment
1- Medical treatment for severe cases
- Nil by mouth
- IV fluids and electrolytes correction
- Parenteral antibiotics for 10-14 days
 Combination of ampicillin + gentamicin + ciprofloxacin
 Or metronidazole + 2nd or 3rd generation cephalosporins

51
 - Most patients with uncomplicated diverticulitis recover with medical
treatment and don't have recurrences
2- Medical treatment for mild cases
- Oral antibiotics for 10-14 days
 Ciprofloxacin 500 mg PO bid or levofloxacin 500 mg qd +
 Metronidazole 250-500 mg PO tid
3- Diverticular abscess
- Percutaneous drainage under U/S or CT guidance + parenteral
antibiotics
4- Surgery (in few patients)
- Indications
 Complications as peritonitis, unresolved obstruction and
colovesical fistula
 Failure to improve after several days of medical therapy
 Recurrence after successful treatment
- Procedure
 A one stage procedure with resection of the diseased segment and
anastomosis is ideal
 If active infection is evident → primary resection with a proximal
colostomy followed several months later by reanastomosis
 Alternatively → the surgeon may elect to perform a proximal
diverting colostomy as the primary operation allowing the
infection and inflammation to resolve before proceeding at a later
date with the resection and anastomosis

51
 Vascular disease of the bowel

Diseases
1- Mesenteric vascular insufficiency
- Occlusive vascular disease
- Non-occlusive vascular disease
 Abdominal angina
 Ischemic colitis
2- Angiodysplasia
3- Vascular enteric fistulas

Angiodysplasia

Definition → ecstatic vascular lesions within the submucosa consisting of arterial,

venous and capillary elements
Site
1- Throughout the GIT tract
2- But most frequent in the cecum and ascending colon
Etiology
1- As a consequence of normal aging
2- Aortic stenosis occurs in up to 15% of patients with bleeding angiodysplasias
but pathogenic association is uncertain
3- As part of hereditary disorder known as Osler Weber Rendu disease in which
telangictatic lesions also are found on the skin, in the nail beds and in the
mucosa of the mouth and nasopharynx
Clinical features
1- Asymptomatic
2- Acute lower GIT bleeding esp. in old age
3- Obscure bleeding
52
 4- May be recurrent episodes of bleeding before diagnosis has established
5- The bleeding may be attributed to another common coexisting disorder as peptic
ulcer or diverticulosis
Investigations
1- Colonoscopy
- An angiodysplastic lesion appears as a submucosal red blush resembling
a spider angioma of the skin
2- Angiography
- An early filling vein
- A vascular tuft of dilated vessels
- A slowly emptying vein
Treatment of bleeding
1- Stop spontaneously in 85% of cases
2- Surgical
- Resection of the segment of bowel that contains the lesion usually the
ascending colon with reanastomosis
- 30% bleed again, either from a new angiodysplastic lesion or from a
lesion that was not resected
3- Colonoscopic
- Electrocoagulation if the lesions can be identified by colonoscopy is an
alternative to surgery

Vascular enteric fistulas

Definition → fistula between a vascular structure and the GI tract

Site
1- Most commonly between an aortic graft and the 3rd portion of the duodenum
months to years after an aortic aneurysm repair
2- Also may develop between an unresected aneurysm and the bowel
3- Less common sites are → sigmoid colon, cecum and esophagus
53
Clinical features
1- Massive hematemesis or hematochezia
2- History of an aneurysm or aneurysm repair is suggestive
3- Herald bleed is characteristic
- Most patients stop bleeding after the initial dramatic hemorrhage, only
to rebleed within hours or days
Investigations
1- Upper GIT endoscopy
- Exclude another bleeding lesion but usually does not identify the fistula
2- Angiography → rarely identifies the fistula
3- CT scan of the abdomen
- May show leaking aneurysm or fistula
4- Barium studies not recommended due to the risk of severe bleeding, also not
likely to identify the fistula
5- High index of suspicion in a patient with an aortic aneurysm or history of
repair is worth more than diagnostic studies
Treatment
Immediate surgical repair of the fistula [extensive vascular reconstructive
surgery] usually indicated after nondiagnostic upper GI endoscopy is performed

Ischemic colitis

Definition → mucosal ischemia in patients with nonocclusive vascular disease of the

bowel
Etiology → Transient low flow through an inadequate vascular system
Site
1- Usually affecting the descending colon, mostly commonly in the region of the
splenic flexure or the sigmoid colon [these areas are the so called wartersheds
between the distributions of the superior mesenteric artery and the inferior

54
 mesenteric artery in the 1st instance and between the inferior mesenteric artery
and the internal iliac artery in the 2nd
2- But may involve any portion of the small and large bowel
Risk factors
1- Elderly patients
2- Patients with congestive heart failure or arrhythmia
3- 10% of patients in the postoperative period after aortic aneurysm repair because
of interruption of inferior mesenteric artery blood flow in the absence of
adequate collateral circulation
4- Oral contraceptive pills
5- Estrogen supplement therapy
6- Raloxifene and pseudoephedrine
Clinical features
1- Abrupt onset of lower abdominal pain + bloody stool
2- Low grade fever may be present
3- Typically the abdomen is soft and there is less tenderness than would be
expected from the degree of abdominal discomfort
4- Outcome
- Self limited course and spontaneous recovery in most patients
- Minority → may initially or eventually have generalized tenderness,
rebound tenderness and absent bowel sounds indicating bowel infarction
and peritonitis
Investigations
1- Plain X ray abdomen
- Shows typical "thumbprints" in the affected area of the bowel
- These are nodular protrusions into the bowel lumen caused by
accumulations of submucosal edema and blood
2- Cautious sigmoidoscopy
- Nonspecific colitis
- Ulcerations
55
 - Soft bluish nodules which are the counterparts of the radiologic
thumbprints
3- Colonoscopy or single contrast barium enema
- Performed if the patient remains stable for 24-48 hours
- Can reveal the affected bowel by confirming the thumbprint appearance
4- Angiography
- Of little value in most patients
- May be useful if surgical treatment becomes necessary
Differential diagnosis [Abdominal pain + rectal bleeding]
1- Ulcerative colitis
2- Crohn's disease
3- Infectious colitis
4- Diverticular disease
Treatment
1- Nil by mouth
2- IV fluids
3- Treatment of underlying disorders if present as heart failure and arrhythmias
4- Antibiotics not indicated unless
- Fever persists or
- Peritoneal signs develop
5- Patients with peritonitis
- Surgical resection of the affected segment with either primary
anastomosis or temporary colostomy
6- Follow up barium enema after 2 months
- Recommended by some experts to determine whether an ischemic
stricture has developed

56
Abdominal angina

Etiology
1- Patients typically have arteriosclerotic disease involving at least 2 of the 3
major visceral arteries (celiac axis, superior and inferior mesenteric arteries)
2- Arteriosclerotic disease of the heart and other blood vessels usually coexists,
sometimes complicated by DM
Clinical features
1- Postprandial mid abdominal pain
- Usually severe and incapacitating
- Occurs several minutes after eating and continues for minutes to hours
- Caused by mesenteric ischemia [the postprandial blood flow simply not
sufficient to meet the increased energy demands of the intestine during
digestion]
2- Weight loss (4.5-13.5 kg) is common
- Patients are reluctant to eat because of pain
- Mild to moderate malabsorption
3- May be nausea, vomiting and diarrhea
4- Examination → evident weight loss and abdominal bruit may be heard
5- Intestinal infarction
- Mau occur in minority of patients after weeks or months
Differential diagnosis [Abdominal pain + weight loss]
1- Cancer pancreas
2- Cancer and other disorders of the stomach, small bowel, colon, gallbladder and
pancreas
Investigations
1- Diagnosis depends on
- High degree of clinical suspicion

57
 - + Absence of evidence for other common causes of abdominal pain and
weight loss [upper GI and small bowel x-ray series, barium enema, U/S
of the gallbladder and abdominal CT scan]
- + An abdominal arteriogram that shows complete or nearly complete
occlusion of at least 2 of the 3 major splanchnic arteries
Treatment
1- Treatment of choice
- Arterial bypass surgery or surgical endarterectomy
2- Alternative in some patients
- Percutaneous endarterectomy under fluoroscopic guidance
3- Rarely if surgically unfit
- Elemental diet or chronic IV alimentation

Occlusive vascular disease (intestinal infarction)

Definition → occlusion of the celiac axis, superior mesenteric artery or inferior

mesenteric artery or their branches
Etiology
1- Arterial thrombosis or embolism
- Most common cause of thrombosis is atherosclerotic vascular disease
- Emboli may accompany MI, ventricular aneurysm, AF, valvular heart
disease or bacterial endocarditis
2- A dissecting aortic aneurysm can occlude one or more mesenteric vessels
3- If collateral is inadequate → acute intestinal ischemia
Clinical features
1- Acute abdominal pain
- Initially → colicky
- If transmural infarction and peritonitis develop → becomes constant and
more severe
2- Fever, tachycardia, hypotension, leukocytosis and bleeding ensue
58
 3- Careful examination to evaluate fro abdominal aneurysm, abdominal bruit and
changes in peripheral pulses
Investigations
1- Laboratory studies
- CBC → may increased
- Serum amylase → may increased (but not > 5 times above normal –
higher elevation suggestive of acute pancreatitis)
- Urinalysis
- Metabolic acidosis may develop if ischemia worsens
2- Plain abdominal X ray
- May show distended loops of bowel with air fluid levels
- Bowel loops may be separated by edema and blood within the bowel
wall
3- Angiography
- Confirm the diagnosis
- But if clinical course is rapid and perforation is suspected, immediate
surgery is indicated
Treatment
1- NGT suction
2- IV fluids and electrolyte replacement
3- Blood transfusion
4- Broad spectrum antibiotics
5- Vasopressors if necessary
6- Definitive treatment → surgical resection of the infracted bowel

59
 Dyspepsia

Definition
1- An upper abdominal discomfort, nausea, heart burn or distension in relation
to meals
2- It may be described as a sense of indigestion
3- Usually originate from the upper GIT
Causes
1- Upper GIT disorders
- Acute gastritis
- Peptic ulcer disease
- Motility disorders e.g. esophageal spasm
- Functional dyspepsia
 Non ulcer dyspepsia
 Irritable bowel syndrome
2- Other GIT disorders
- Biliary tract disease
- Pancreatic disease
- Hepatic disease
- Cancer colon
3- Systemic diseases e.g.
- Renal failure
- Hypercalcemia
4- Drugs e.g.
- NSAIDs
- Iron
- Steroids
5- Others
- Alcohol
- Psychological
61
Functional dyspepsia
1- Definition → persistent dyspepsia for which no structural or biochemical cause
can be found
2- Include
- Reflux like → e.g. heart burn, relieved by antacid
- Ulcer like → localized epigastric pain and nocturnal pain is dominant
which relieved by vomiting and antacids
- Dysmotility like → upper abdominal discomfort (non painful) is
dominant with nausea, belching and abdominal distension
3- Other symptoms include early satiety, nausea and fullness. It may be
associated with H. pylori infection
4- Investigations
- Endoscopy to exclude mucosal biopsy
- U/S may detect gall stones
5- Treatment
- Antacids, H2 blockers
- Prokinetics
- Low dose amitriptyline may be of value
- H. pylori eradication is controversial

61
 Approach to small bowel bleeding

Causes
1- Angioectasias or arteriovenous malformations :
- 30 - 40% of causes (usually the age > 50yr)
- These are abnormal blood vessels that lie within the wall of the small
bowel
- Associated with chronic kidney disease and valvular heart disease
2- Ulcers of the small bowel
- Mainly due to NSAIDs
3- Polyps
4- Crohn's disease
5- Benign and malignant tumors
6- Blood vessels associated with certain heart conditions or cardiac implantable
device
Incidence → about 5% of all GIT bleeding
How is the small bowel examined?
1- The first step is endoscopy and/or enteroscopy.
2- If that fails to find the source of bleeding, a common next step is capsule
endoscopy.
3- X-ray options include a small bowel follow-through, or CT scan of the small
bowel.
4- Deep small bowel enteroscopy can now be performed using special scopes
with inflatable balloons and/or overtubes.
5- The final option, which is usually used only if other methods have failed, is
intraoperative enteroscopy.
Investigations
1- Standard endoscopy (OGD and colonoscopy)
- Treat lesions
- To obtain biopsies
62
 - To mark the location of a lesion with a tattoo to aid a surgeon in
locating it.
- OGD capable of examining the esophagus, stomach and the first portion
of the small bowel, known as the duodenum. Colonoscopy can reach
ileum
2- Enteroscopy
- Can reach the middle portion of the small bowel (jejunum)
- Both biopsy and endoscopic therapy can be performed
3- Capsule endoscopy
- Indicated after ruling out a bleeding source from the stomach or colon
- The capsule is generally safe and easy to take, but can get stuck in the small
intestine if there has been prior abdominal surgery causing scarring or other
conditions that cause narrowing of the small intestine.
- If the capsule gets stuck, endoscopic or surgical removal is necessary
- CE-negative cases were the result of failure to detect lesions in the proximal small
bowel, a Roux en-Y loop and diverticula
- The likelihood of identifying a potentially clinically important lesion by CE is
greater than by either enteroscopy or small-bowel barium radiography
- Visualization of additional vascular and inflammatory lesions
- The best approach would be to use CE to triage patients for deep enteroscopy, so
that a lesion identified by CE can be specifically investigated with DBE, allowing
the endoscopist to better focus DBE
4- Standard small-bowel follow through
- Detect mass lesions (20-25% of small bowel bleeding caused by
abnormalities in the intestinal wall as tumors)
- Cannot detect AVMs and many mucosal lesions
5- Enteroclysis study
- Can detect abnormalities missed by small bowel follow through test but
it can be an uncomfortable examination
6- CT enterography
7- Deep small bowel enteroscopy
- Indications
63
  It is usually reserved for cases in which a source of small bowel
bleeding out of reach of a standard enteroscope had been found
on either an x-ray or capsule endoscopy
- Options → single-balloon or double-balloon enteroscopy, If we see
bleeding during the capsule endoscopy test, we often recommend
a double balloon enteroscopy
8- Intraoperative enteroscopy or colonoscopy
- Usually reserved for cases where other methods have failed to find or
treat the source of bleeding (permits visualization of most or all of the
small intestine).
- Allows to treat the cause of bleeding at the time of discovery (for
AVMs), or to remove masses or polyps that are found
9- Mesenteric angiography
- Useful in evaluation of patients with severe bleeding, often requiring
blood transfusion.
- Can treat vascular lesions (embolization or vasopressin infusion)
10- Provocative angiography
- Indicated in patients with recurrent obscure bleeding that is not active
and in whom diagnostic options have been exhausted
- Bleeding is reactivated or augmented by the use of vasodilators,
anticoagulants and/or thrombolytics followed by visceral angiography
Treatment
General management of GIT bleeding ®
Specific treatment
1- Vascular ectasias (AVMs) [large and discrete):
- Endoscopy/enteroscopy
 Thermal therapy (for example, laser, bipolar electrocoagulation or
bicap)
 Banding
 Injection therapy
64
  Argon plasma coagulation
- Angiographic embolization therapy
 For massive and ongoing bleeding [block the culprit blood vessel
using special particles /material]
 Recurrent bleeding after endoscopic or angiographic therapy is
uncommon
- Surgical therapy
 In rare cases where numerous AVMs are present within a
segment of small bowel, the segment of small bowel may need to
be removed surgically.
- Hormonal therapy [controversial]
 Estrogen and/or progesterone containing compounds
 The somatostatin analogue octreotide: has been examined as a
therapy for diffuse vascular ectasia bleeding at a dose of 0.05-1.0
mg subcutaneously per day, this compound was effective and had
no side effects.
 Antifibrinolytic agents aminocaproic acid and tranexamic acid
and the synthetic steroid danazol have been reported to control
bleeding
- Intraoperative enteroscopy:
 Surgical resection of these lesions does not always prevent
recurrent bleeding.
- The treatment of diffuse and multiple vascular ectasias are difficult and
less successful
2- Gastric vascular ectasia
- Local thermal endoscopic therapy
- TIPS has no role
3- Polyps
- Endoscopic or surgical removal followed by histological examination

65
4- Ulcer disease
- Stop NSAIDs
- Ulcers may be treated by conventional endoscopic means
5- Neoplastic lesions
- Treatment is specific to the type of tumor
- Can be biopsied (some removed endoscopically) and Others, typically
require surgical removal
- While benign tumors do not necessarily need to be removed in all cases,
if they are causing significant blood loss removal is usually
recommended
6- Crohn's disease → ®
7- Portal hypertensive gastropathy [↓ portal pressure]
- Nonselective β-blockers
- TIPS are highly effective
8- Aortoenteric fistulas
- Extensive reconstructive vascular surgery (mortality > 50%)
9- Hemobilia or hemosuccus pancreaticus
- Treatment depends on the underlying etiology of the bleeding
- Angiographic embolization is preferred approach
- Surgical intervention may be required

66
Specific management of LGIB

1- Principles
- No medical treatments [in most causes]
- Usually no need for emergent colonoscopy
- If stable but continued bleeding can do “rapid purge” and colonoscopy
can be done in 6-12 hours
- Proctosigmoidoscopy and Colonoscopy reveals cause in > 70% of cases
→ if no obvious cause, selective arteriography is done both for
diagnosis and possible therapeutic measures
- Tools used
 Epinephrine injection
 Cautery
 Hemoclip
 APC (argon plasma coagulation), Endoloop
 Surgery
2- Treatment of angiodysplasia → ® important
3- Treatment of diverticular bleeding → ® important
4- Treatment of ischemic colitis → ® important
5- Treatment of colorectal cancer → ®
6- Treatment of colonic polyps → ®
7- Treatment of UC & Crohn's disease → ®
8- Treatment of infectious colitis
- Ciprofloxacin, azithromycin, co-trimoxazole, ceftriaxone, or
metronidazole
9- Treatment of hemorrhoids
- A high-fiber diet, stool softeners, and avoidance of straining at stool and heavy
lifting may be sufficient to treat mild hemorrhoidal symptoms
- Warm baths twice a day and anal lubrication with glycerine suppositories provide
further comfort.

67
 - Addition of medicated suppositories, such as Anusol-HC (containing
hydrocortisone), may help reduce associated inflammation. However, steroid
containing medications should be limited to 2 weeks of continuous use to avoid
atrophy of the anal tissues
- Rubber-band ligation is usually the first definitive treatment.
- Injection of hemorrhoids with sclerosing solutions, dilatation of the anal sphincter
under anesthesia, electrocoagulation, and laser coagulation are alternatives if rubber
banding is ineffective.
- In patients whose hemorrhoids are severe and refractory to these treatments, surgical
excision of the hemorrhoidal plexus may be necessary.
10- Treatment of anal fissures
- The treatment of anal fissure is similar to that of hemorrhoids: high-bulk diet,
stool softeners, warm baths, and lubricating suppositories. Most fissures heal
on this regimen
- Chronic anal fissures that are not due to IBD may require dilatation of the
anus, sphincterotomy, or excision of the fissure

68
Approach to abnormal liver chemistries

Causes and screening for mild ↑ serum ALT and AST [< 5X
normal]
1- Alcohol abuse
- History + Elevation of AST> ALT esp. a ration > 2:1 (AST rarely
exceeds 300) with a 2 fold elevation of GGT
2- Hepatotoxic medications and herbals → history
3- Chronic Hepatitis B
- HBsAg + positive IgM anti HBc → acute
- HBsAg + negative IgM anti HBc → chronic
4- Chronic Hepatitis C → anti HCV and PCR
5- NASH
- Ratio of AST:ALT usually < 1
- U/S, CT, MRI
- More common in women, associated with obesity, hyperlipidemia and
DM type 2
6- Hereditary hemochromatosis
- Serum iron and TIBC to calculate iron saturation (serum iron/TIBC) →
if saturation > 45% → check ferritin, a ferritin level > 400 in men and >
300 in women supports the diagnosis
- Liver biopsy and genetic testing should follow
7- Alpha -1 antitrypsin deficiency → AAT level
8- Cirrhosis → AST > ALT
9- Acute viral hepatitis (A-E), EBV, CMV
10- Celiac disease → transglutaminase antibody & endomyseal IgA antibodies
11- Nonhepatic causes
- Thyroid diseases
- Myopathy, strenuous exercise
- Hemolysis
69
 - Strenuous exercise
- Adrenal insufficiency, anorexia nervosa
Causes and screening for marked ↑ serum ALT and AST [>15 X
normal]
1- Acute viral hepatitis (A-E) and HSV
2- Drug induced hepatotoxicity [Acetaminophen overdose is the most common
cause of drug induced fulminant hepatic failure]
3- Ischemic hepatitis
- History of acute left ventricular failure
- AST > ALT (up to 100 times normal), marked ↑ LDH with ALT/LDH
ration < 1.5
4- Autoimmune hepatitis
- More common in young women
- Screen with IgG level (80% have hypergammaglobulinemia) followed
by ANA and SMA
- Liver biopsy to confirm the diagnosis
5- Wilson's disease
- Serum ceruloplasmin ↓, ophthalmologic exam. For Kayser Fleischer
rings
- Occasionally, a 24 hour urine for copper excretion
6- Acute bile duct obstruction
- Screen with an U/S, CT, MRCP initially
- ERCP can be therapeutic
7- Acute Budd-Chiari syndrome
- Screen with Doppler U/S
Approach to ↑ alkaline phosphatase
1- History and examination
- Pruritus, cholestasis, drugs
- Pregnancy, bony symptoms, renal diseases
2- Measure GGTP or 5' nucleosidase levels [5NT is superior]
71
 - Normal → extrahepatic source
 Bone → as paget's disease , osteoblastic bone metastases
 Intestine → as small bowel obstruction
 Normal pregnancy
 Renal disease
- ↑ → hepatobiliary disease
3- U/S abdomen
- Gall stones → cholecystectomy and bile duct exploration if indicated
- Focal lesion (s) → CT and/or MRI, biopsy
- Biliary tract abnormalities ( e.g. dilated bile duct) → ERCP or MRCP
→ if PSC is diagnosed → colonoscopy to screen for ulcerative colitis
- Normal
 Positive AMA → liver biopsy [esp. BPC]
 Negative AMA → ACE level, serological tests for hepatitis, AFP
4- If all the above negative + persistent elevation
- Observe for mild elevation
- Liver biopsy for chronic (> 6 months) elevation
5- Hepatobiliary causes
- Infiltrative liver disease → tumor, abscess, granulomas or amyloidosis
- Mild elevation → hepatitis and cirrhosis
- Higher elevation
 Biliary obstruction
 PSC, PBC and 2ry sclerosing cholangitis (in severely ill patients)
 Cholestatic drug reactions
 Sepsis and HIV

LDH
1- The ALT: LDH ratio < 1.5 → ischemic hepatitis and acetaminophen toxicity
2- The ALT: LDH ratio ≥ 1.5 → acute viral hepatitis
3- Also LDH increased in hemolysis and cancer
71
Globulins
1- Elevated IgG → suggest autoimmune hepatitis
2- Elevated IgM → suggest PBC
3- Elevated IgA → suggest alcoholic liver disease
Albumin
1- ↓ level indicate severe liver disease (synthetic function)
2- ↓ in chronic liver disease [also in renal and GIT losses]
3- Normal in acute liver disease → half life about 20 days
4- Prealbumin → sensitive marker of liver function in acute acetaminophen
overdose [short half life = 1.9 days]
Bilirubin → see jaundice

72
Drugs & infections during pregnancy

Antibiotics
1- Safe drugs
- Penicillins, amoxicillin, ampicillin
- Cephalosporins
- Erythromycin (not estolate), azithromycin, spiramycin, clindamycin
- Sulfa (before 3rd trimester) : give folic acid to prevent anemia
- Nitrofurantoin (before 3rd trimester)
2- Contraindicated drugs
- Tetracycline and doxycycline
 Fatty liver and possible renal damage in the mother
 Risk of pancreatitis in the mother
 Get deposited in fetal bones and retard their growth
 Also affect teeth causing them to be discolored and deformed
- Erythromycin estolate → hepatotoxicity in pregnant women
- Chloramphenicol → Gray baby syndrome
- Aminoglycosides → fetal 8th nerve damage
- Metronidazole [CI in 1st trimester] → teratogenic
- Sulfonamide [CI in last trimester esp. last 2 weeks and neonates]
 May increase bilirubin level in the newborn leading to kernicterus
- Nitrofurantoin [CI in last trimester]
 Can cause hemolytic anemia in newborns
 Related to immature liver and G6PD ↓
3- Drugs have only small risk
- Fluoroquinolones
- Clarithromycin
- Vancomycin
- Gentamicin
- Imipenem

73
Antituberculous-leprosy drugs
1- Safe
- Ethambutol
2- Contraindicated
- Isoniazide (INH)
 Neuropathy and seizures in the fetus
 Liver damage in mother
- Thalidomide → seal like limbs and other defects to the fetus
3- Only small risk
- INH
- Rifampicin
- Pyrazinamide
- Dapsone
Antiviral drugs
1- Safe
- Ritonavir, valacyclovir, ramciclovir, saquinavir
2- Contraindicated
- Ribaverin → teratogenic
3- Only small risk
- Acyclovir, ganciclovir, foscarnet
- Lamivudine, zidovudine
- Interferon alpha, amantadine
Anti- parasitic drugs
1- Safe
- Praziquantel
2- Contraindicated
- Metronidazole in 1st trimester
- Quinine
3- Only small risk
- Albendazole, mebendazole, thiabendazole
- Ivermectin
74
 - Pentamidine, pyrantel
- Mefloquine, chloroquine, primaquine
Antifungal drugs
1- Safe
- Topical antifungals
2- Avoid in 1st trimester if possible
- Fluconazole, clotrimazole, terbinafine
3- Contraindicated [possible teratogenicity and hepatotoxicity]
- Ketoconazole
- Griseofulvin
Vaccines contraindicated
1- Measles, mumps and rubella vaccine
2- Yellow fever vaccine
3- Varicella vaccine
4- Small pox vaccine
5- TC-83 Venezuelan equine encephalitis vaccine
[risk if vaccinated within 4 weeks of conception]

Vitamins
1- Safe → folic acid and vitamin B6
2- Contraindicated → vitamin A and its derivatives (birth defects and miscarriage)

Quinolones

Structure → 4- quinolone 3- carboxylate related to naldixic acid

Action
Bactericidal via inhibiting DNA synthesis [interfere with the activity of DNA gyrase,
an enzyme needed for replication of bacterial DNA]
Metabolism
1- Rapid absorption (reaches peak serum conc. In 2 hours)
2- Food may decrease its absorption
3- Metabolized in the liver and excreted in the bile and urine

75
Spectrum
1- Gram –ve organisms
2- New members are active against pseudomonas and gram +ve cocci
Members
1- 1st generation → nalidixic acid, oxolonic acid
2- 2nd generation → pipemidic acid
3- 3rd generation → norfloxacin, ofloxacin, ciprofloxacin, pefloxacin, levofloxacin
Indications
1- Urinary tract infections (E.coli, enterococci, staph. Saprophyticus and pseudomonas
aerogenosa)
2- Enteric fever (ciprofloxacin 500-750 mg twice daily for 7-10 days)
3- Traveller's diarrhea
4- Enteritis including salmonellae, shigellae, campylobacter, yersinia, E.coli and vibrios
5- Gonococci, meningococci and H. influenzae
Doses
1- Ciprofloxacin 250-500-750 mg twice daily
2- Levofloxacin 250-500 mg once daily
3- Pefloxacin 400 mg twice daily
[these drugs also available as IV infusion]
Side effects
1- GIT upset with nausea, vomiting, diarrhea, dyspepsia and abdominal pain
2- Headache, dizziness and fatigue
3- Hypersensitivity reactions as urticaria and anaphylaxis
4- Agranulocytosis (leucopenia, anemia, neutropenia), eosinophilia
5- Crystalluria may occur
6- Avoided in pregnancy, lactation ? and children as they may cause arthropathies in
children ?

76
Recurrent fevers

Definition
1- A symptom in which fever fails to recede and keeps coming back in the form of
recurrent bouts
2- Often associated with vomiting, anorexia, body aches, sweating, chills and irritability
Causes
1- Mononucleosis disease
- CMV
- EBV
- Toxoplasmosis
2- Typhoid fever
3- TB
4- Brucellosis
5- Borreliosis
6- Periodic fever syndrome see below
7- Malaria
8- Cholera
9- Lymphoma and cancer
10- Hepatitis
11- HIV
12- SLE
13- Q fever
14- PID
15- Rat bite fever
16- Sarcoidosis

Investigations and treatment → according to the cause

Periodic fever syndrome

Definition → these are a set of genetic disorders where the person experiences recurrent
episodes of fever accompanied by various other inflammatory symptoms hence they are also
known as auto inflammatory syndrome
Types
1- Hereditary
- FMF
- Hyper IgD syndrome

77
 2- Non hereditary
- PFAPA syndrome
- Schnitzler syndrome

Familial Mediterranean fever

Etiology
1- Inherited as an autosomal recessive disease
2- The gene has been localized to chromosome 16 (called MEFV gene)
3- It affects the protein called pyrin (chemotactic factor inactivator) which plays an
important role of regulating and controlling the inflammation in the body → FMF
attacks
Clinical features
1- Attacks of fever + serositis e.g. peritonitis (abdominal pain, tenderness, vomiting),
pleurisy (chest pain), arthritis
2- Typical attack lasts for 12-72 hours but the arthritis up to one week
3- May be complicated by renal amyloidosis
Investigations
1- MEFV gene direct analysis
2- During the attack → ↑ ESR, CRP, fibrinogen and amyloid A
3- X ray chest showing effusion in some cases
4- Renal biopsy may show amyloidosis in long standing cases
Treatment
1- During the attack
- NSAIDs
- Colchicines one tab. (0.6 mg) Every 2 h till 4 tablets or diarrhea then
one tab. Every 12 h
- If no response → interferon alfa or tumor necrosis factor blocking drugs
2- Regular treatment with colchicines 1-2 mg/day for life → prevent or decrease
the frequency of the attackes and prevent development of renal amyloidosis
3- Follow up every 3 months
- Urinalysis for protienuria
- Blood urea and creatinine
- Abdominal U/S for assessment of the kidney
78
Hyper IgD syndrome
1- Very rare
2- Characterized by recurrent fever, headache, abdominal pain, skin rash and
lymphadenopathy
PFAPA syndrome
1- The most common cause of recurrent fever in children (1 month to 5 years) an
areas of Europe and America
2- Characterized by pharyngitis, adenitis, periodic fever and aphthous stomatitis
Schnitzler syndrome
1- Unknown cause
2- Delayed diagnosis because of varied confusing symptoms
N.B. Pel – Ebstein fever
1- Fever lasting 3-10 days followed by afebrile periods of 3-10 days
2- It is classic for Hodgkin's disease and other lymphomas

Management of Unilateral edema

Causes
1- DVT
- Causes
 Post partum, pregnancy
 Post operative or fractures
 Varicose veins
 Heart failure
 Phlebitis
 Malignancy
 Nephrotic syndrome
 Causes of thrombophilia: as protein C & S deficiency
- Site : usually iliofemoral or popliteal veins

79
 - Features
 Unilateral pitting edema of LL
 Tender calf muscle and tenderness along the course of the
affected vein
 +ve Homan sign : pain on the calf on dorsiflexion of the foot (not
diagnostic)
 May be heart failure (thromboembolic)
 Duplex on superficial and deep venous system is diagnostic
- DD of tender calf muscle
 Rupture plantaris
 Cellulitis
 Diabetic neuropathy
 Osteomyelitis
 Rupture baker cyst
- Treatment
 Heparin 5000-10,0000 u iv as a loading dose then 1000 u /h iv
infusion drip for 7-10 days or till improvement. Follow up by PT
is adjusted to be (1.5-2.5) of the control value
 Or heparin 5000-7500 u/iv/ 6 hrs
 Or heparin 10,000 u SC/ 8hrs
 Then start oral treatment with Warfarin 2.5-7.5 mg/day for 3-6
months. The dose adjusted accprding to PT to be (1.5-2) of the
control value or to reach an INR value (2-3.5) according to the
need
2- Lymphedema (non pitting)
- Filariasis ‫® مهم جدا‬
- Post mastectomy (UL)
3- Cellulitis
- Etiology

81
  GABHS (streptococcus pyogenes)
 S.aureus
 H.influenzae in children
 Pasturella multocida from dog or cat scratch or bite
- Features
 Tenderness, swelling, redness and hotness of the affected skin
+edema
 Ill defined edge
 Fever, chills and sweating
 Regional lymphadenopathy
 Crepitus is noted with anaerobic organisms
 Helping lab. → leukocytosis, ↑ ESR, CRP
 Blood culture in case of bacteremia or culture from abscess if
formed or skin biopsy is confirmative
- Treatment
 Mild local symptoms → outpatient oral antibiotics for 10 days
with reevaluation after 48 h
 If no improvement or lymphangitis or systemic symptoms →
admission for iv antibiotics
 Any patient with crepitus, circumferential cellulitis or necrotic
appearing skin → requires rapid surgical intervention
 Antibiotics as
© Amoxicillin clavulinate 500-875 mg PO pid
© Clindamycin 150-300 mg/dose PO q6-8h; not to exceed 1.8
g/day or 600 mg iv divided q8h not to exceed 4.8 g/day
© Penicillins
4- Trauma
5- Chronic venous insufficiency
- LL, signs of varicose veins, ulceration and pigmentation of the leg
6- Angioneurotic edema

81
 - Non pitting, sudden onset, self limited but mainly affecting the face
(lips) asymmetrical, history of allergy or insect bite
Chloramphenicol

Action → potent inhibitor of bacterial protein synthesis (bacteriostatic)

Spectrum → many gram +ve and gram –ve bacteria
Indications
1- Typhoid fever ®
2- Bacterial meningitis ®
3- Tularaemia ®
4- H.influenzae infections
Dose
1- 50 mg/kg/day orally [rectal dose is double oral dose and parenteral dose is half
the normal dose]
2- Thiophenicol, cidostin
Side effects
1- Nausea, vomiting and diarrhea
2- Fatal grey baby syndrome in newborns manifested by cyanotic grey color of
the skin, vomiting, flaccidity, hypothermia and collapse [due to failure of the
liver conjugation with inadequate renal excretion of chloramphenicol
metabolites)
3- Haemopoietic system [bone marrow suppression]
- Anemia is dose related and reversible
- Hemolytic anemia in G6PD deficient individuals
- Aplastic anemia (1:5000) is a specific genetically determined individual
defect, irreversible and more frequent with prolonged or repeated use
- Leukemia
4- Prolonged use may cause reticulosis
5- Hypersensitivity and encephalopathy

82
Azole group of antifungals

Mechanism of action
Alter the fungal cell membrane by blocking biosynthesis of ergosterol
resulting in leakage of cell contents
Toxicity
1- Transient abnormalities of liver function
2- Severe hepatotoxicity is a rare complication of ketoconazole therapy
Fluconazole
1- Antifungal activity
- Candida spp., Cryptococcus neoformans, histoplasma capsulatum
- Ineffective against aspergillus and mucor spp.
2- Pharmacokinetics
- Oral and iv preparations are available
- Good penetration into various body sites and excreted unchanged in
urine
3- Uses
- Mucocutaneous and invasive candidiasis
- Cryptococcal infections
- Prophylaxis in immunocompromised patients e.g AIDS patients and
transplant recipients
Itraconazole
1- Antifungal activity
- Candida, histoplasma capsulatum
- Aspergillus spp. And dermatophytes
2- Pharmacokinetics
- Only available orally but well absorbed
- It is highly protein bound and degraded into a large number of inactive
metabolites and excreted in bile
83
 3- Uses
- Dermatophytoses
- Mucocutaneous and invasive candidiasis
- Aspergillosis
- Histoplasmosis, blastomycosis
Ketoconazole
1- Available as oral or topical forms
2- Not active against aspergillus spp.
3- The principal use is topical therapy for dermatophyte infections and cutaneous
candidiasis
Miconazole
1- Available as topical, oral and parenteral forms
2- Used principally as topical therapy for dermatophyte infections and cutaneous
candidiasis
Voriconazole
1- Antifungal activity
- Aspergillus spp. And candida spp. And other mycoses
2- Pharmacokinetics
- Oral and iv preparations available
- Cleared mainly by hepatic metabolism
3- Side effects
- Visual disturbances
- Drug interactions e.g. warfarin, ciclosporins
4- Uses → aspergillosis (superior to amphotericin)

84
Emerging fevers

Major agents appeared in the 21st century

1- Ebola hemorrhagic fever ®
2- Marburg hemorrhagic fever ®
3- Avian flu ®
4- SARS (severe acute respiratory syndrome) ®
5- West nile virus ®
6- Bovine spongiform encephalopathy
7- Human monkeypox

Avian (bird) flu

Definition
1- Avian influenza is flu infection in birds. The virus that causes the bird infectin
can change (mutate) to infect humans.
2- Such mutation could start a deadly worldwide epidemic.
Cause
1- The first avian influenza virus to infect humans occurred in Hong Kong in 1997.
The epidemic was linked to chickens and classified as avian influenza A
(H5N1).
2- Human cases of avian influenza A (H5N1) have since been reported in Asia,
Africa, Europe, Indonesia, Vietnman, the Pacific, and the near East. Hundreds
of people have become sick with this virus. Slightly more than 60% of those
who became ill have died.
Risk factors
1- Farmers and others who work with poultry
2- Travelers visiting affected countries

85
 3- Those who touch an infected bird
4- Those who eat raw or undercooked poultry meat, eggs, or blood from infected
birds
5- Health care workers and household contacts of patients with avian influenza
The virus and spread
1- The avian flu virus (H5N1) has been shown to survive in the environment for
long periods of time.
2- Infection spread by droplet and by touching contaminated surfaces.
3- NO human to human spread
4- Birds who were infected with this flu can continue to release the virus in their
feces and saliva for as long as 10 days.
Clinical features
1- Symptoms of avian flu infection in humans depend on the strain of virus.
2- Suspicion → flu-like symptoms within 10 days of handling infected birds or
traveling to an area with a known avian flu outbreak.
3- Infection with the H5N1 virus in humans causes typical flu-like symptoms,
which might include:
- Cough (dry or productive)
- Diarrhea
- Difficulty breathing
- Fever greater than 100.4°F (38°C)
- Headache
- Malaise
- Muscle aches
- Runny nose
- Sore throat
4- Ask about chronic medical diseases as kidney, liver and heart diseases
Complications
1- Acute respiratory distress
2- Pneumonia

86
 3- Organ failure
4- Sepsis
Investigations
1- Tests to identify the avian flu exist but are not widely available. A test for
diagnosing strains of bird flu in people suspected of having the virus gives
preliminary results within 4 hours. Older tests took 2 to 3 days.
2- Nasopharyngeal culture
3- White blood cell differential
4- Chest x-ray
Treatment
1- People with suspected symptoms of bird flu (avian flu) will be advised to
stay at home or will be cared for in hospital (in isolation from other
patients).
- To reduce the chance of an avian flu virus mixing with a human flu
virus, which would create a new virus that may easily spread.
2- The patient may be kept in isolation for up to 10 days. The main
recommendations are:
- Rest
- Drinking plenty of fluids and eating healthily
- Medications to help treat fever and pain, such as aspirin
and paracetamol (aspirin should not be taken by children under the age
of 16)
3- Antiviral drugs
- Action → stop viral multiplication,
- Effect → may help reduce the severity of the condition, prevent
complications and help improve the chances of survival.
- Drugs → oseltamivir (Tamiflu) or zanamivir (Relenza) or Peramivir
(Actrapid)

87
 - These drugs may make the disease less severe if starting within 48 hours
after symptoms onset (however, it should be taken if the time after onset
> 48 h)
4- Ineffective antiviral drugs
- Amantadine and rimantadine (resistant to H5N1)
5- 2ry bacterial pneumonia require
- IV antibiotics
- Oxygen and may mechanical ventilation
6- Prophylaxis
- Indications
 People who could have been exposed to bird flu viruses – for
example other household members, healthcare workers or people
who have had close contact with infected birds.
- Drugs and course
 Oseltamivir
 The course of medication should begin as soon as possible after
exposure to the virus and continue for 7 to 10 days after last
known exposure.
Prevention
1- The U.S. Food and Drug Administration has approved a vaccine to protect
humans from the avian flu. Experts say the vaccine could be used if the current
H5N1 virus starts spreading between people.
2- Travelers should avoid visits to live-bird markets in areas with an avian flu
outbreak.
3- People who work with birds who might be infected should use protective
clothing and special breathing masks.
4- Avoiding undercooked or uncooked meat reduces the risk of exposure to
avian flu and other foodborne diseases.

88
 Fever of unknown origin

Old definition
1- Fever ≥ 38 C on several occasions
2- For > 3 weeks duration
3- And no diagnosis established despite 1 week of intensive evaluation
- CBC, urine and stool examination
- Chest X ray and abdominal U/S
- Widal test
Recent definition [categories]
1- Classic type
- It meets the original criteria of FUO, with evaluation of at least 3 days
in the hospital, 3 outpatient visits or 1 week of logical and intensive
outpatient testing
2- Nosocomial
- Fever occurring on several occasions in a patient who has been
hospitalized for at least 24 h and has not manifested an obvious source
of infection that could have been present before admission, a minimum
of 3 days of evaluation is needed
3- Immune deficient (neutropenic)
- Recurrent fever in a patient whose neutrophil count is ≤ 500/mm and
has been assessed for 3 days without establishing diagnosis
4- HIV- associated
- Recurrent fevers over a 4 week period in an outpatient or for 3 days in a
hospitalized patient with HIV infection

89
Common causes
Classic
1- Infections (30-40%):
- Tuberculosis esp. extra pulmonary
- Mal-treated typhoid fever
- Brucellosis
- Infective endocarditis
- Abdominal abscesses (as amoebic liver, subphrenic)
- Pelvic abscesses
- Dental abscesses
- CMV
- EBV
- HIV
- Osteomyelitis
- Septic arthritis in prothetic joint
- Chronic salmonellosis
- Prostatitis
- Sinusitis
- Lyme disease
2- Neoplasms (20-30%)
- Chronic leukemia
- Lymphoma
- Metastatic cancers
- Renal cell carcinoma
- Bronchogenic carcinoma
- Colon carcinoma
- Hepatoma
- Multiple myeloma and other myelodysplastic syndromes
- Pancreatic carcinoma
- Sarcomas
3- Autoimmune conditions (10-20%)
- Adult Still's disease
- SLE
- Rheumatoid arthritis
- Rheumatic fever
91
 - Vasculitis
- Polymyalgia rheumatica
- Temporal arteritis & Reiter's syndrome
- Inflammatory bowel disease
4- Miscellaneous (15-20%)
- Drug fever e.g. penicillins. There is usually rash, arthralgia and eosinophilia
- Cirrhosis
- FMF
- Sarcoidosis
- Thyrotoxicosis
- Hepatitis (alcoholic, granulomatous or lupoid-autoimmune)
- Hemolytic blood diseases
- Deep venous thrombosis
- Factitious fever
 Switching thermometers
 Ingestion of pyrogenic material as milk
 Taking hot drinks before temperature recording
5- Undiagnosed (5%)
- The cases recover spontaneously or with antibiotics or anti-inflammatory
drugs or steroids or the fever remains recurrent
Nosocomial
1- Septic thrombophlebitis
2- Pulmonary embolism
3- C.difficile enterocolitis
4- Drug induced fever in patients with nasogastric or nasotracheal tubes
5- Sinusitis also may be a cause
Immune deficient (neutropenic)
1- Occult infections caused by fungi, such as hepatosplenic candidiasis and aspergillosis
must be considered
2- Less commonly: HSV may be the inciting organism, but this infection tends to present
with characteristic skin findings
HIV associated
1- Mycobacterium avium complex
2- Pneumocystis carinii pneumonia
3- CMV
4- Lymphomas, kaposi's sarcoma and drug induced fever

91
Diagnosis of FUO case
1- History:
- Fever, weight loss, night sweats, headaches, rashes,…
- Drug history
- Occupational history
- Sexual history
- Family history
- Travel history
- Immunization status
- Recreational habits
- Nutrition
- Animal contacts including possible exposure to ticks and other arthropods
- Previous illnesses as TB, leukemia, infective endocarditis,…
2- Physical examination
- Documentation of prolonged fever and exclusion of factitious fever
- Pattern of fever of little help
- Relative bradycardia as typhoid, legionnair’s disease, leptospirosis,…
- Skin lesions, lymphadenopathy, heart murmur, arthritis
- Abdominal masses, liver, spleen, pelvic organs in females and testis in
males,…
- Neurologic deficits
3- Laboratory tests
- CBC
 Anemia → may suggest serious underlying disease
 Leukemia
 Leukocytosis with increased bands → suggest occult bacterial
infection
 Direct examination of blood smear → diagnose malaria and
spirochetal diseases
 Lymphocytosis with atypical cells → suspect herpes virus
infection
 Lymphopenia → HIV
92
 - Urinalysis → UTI and malignant tumors of the urinary tract
- Liver enzymes for hepatitis e.g. granulomatous

- Serology
 ELISA for CMV antibodies and other viral infections [EBV,
HIV]
 Toxoplasmosis
 Brucellosis
 Amoebiasis
 Chlamydial infections
- ESR higher elevation
 Malignancy
 Reumatological as PMR, GCA, SLE,…
 TB and other chronic infections
- ANA, anti-DNA, RF, anti-CCP
- Culture
 Blood culture for infective endocarditis, typhoid fever
 Sputum. Urine, stool cultures
 CSF culture, culture of peritoneal or pleural fluids, fluids from the
liver, bone marrow and lymph nodes
 Culture first for aerobic and anaerobic bacteria, further evaluation
require culture for mycobacteria, fungi
- Tuberculin test
- Brucella agglutination test
- Widal test
- Paul Bunnel test
- TSH and Thyroxine level → thyroiditis, hyperthyroidism
4- Imaging studies
- Chest X ray → TB, sarcoidosis,malignancy, pneumocystis carinii
pneumonia

93
 - U/S → for suphrenic, pelvic or liver abscesses
- CT pelviabdominal and chest → abscess, malignancy
- Barium enema or follow through may be indicated → IBD, tumors,
malabsorption pattern
- MRI brain → malignancy, autoimmune conditions
- Venous Doppler study → venous thrombosis
5- Endoscopic examination
- Upper endoscopy, colonoscopy, laryngoscopy, bronchoscopy
- MRCP or ERCP may be indicated
6- Radionuclide scanning
- Gallium or Tc (indium) labeled leucocytes → diagnose occult abscess
- Ventilation and perfusion radionucleotide scan → pulmonary emboli
- Pulmonary angiography → if suspect pulmonary emboli despite
negative scanning studies
- Technetium Tc 99m bone scan → infections of bones and soft tissue as
osteomyelitis
7- Biopsies
- Bone marrow for leukemia and other hematological malignancies
- Liver for chronic hepatitis
- Lymph nodes for lymphoma, TB
- Small and large bowel for tumors, IBD, causes of malabsorption
- Other tissues as the lung for sarcoidosis
8- Laparoscopy
- May be required to confirm gynaecological causes e.g. PID or TB
peritonitis
9- Laparotomy
- Rarely indicated e.g. when imaging are non diagnostic and an intra-
abdominal source is suspected
10- Therapeutic trials
- Anti-TB drugs e.g. INH and ethambutol
- Anti-rheumatic drugs
94
 - Metronidazole for amoebic liver abscess
- Chloroquine in suspected malarial infection

Algorism for FUO case

1- Complete history and physical examination → positive findings → order
appropriate and specific diagnostic tests
2- If no findings → ESR, CBC, urinalysis, urine culture, blood culture, tuberculin
test, chest X ray, liver function tests and electrolytes → if positive results →
order appropriate follow up and diagnostic testing
3- If no positive results → abdomino-pelvic CT with contrast → assign to most
likely category
4- Infectious
- Urine and sputum cultures fir AFB, VDRL, HIV test, serology for
CMV, EBV, ASOT (geographically specific testing) → diagnosis is
clear
- If diagnosis not clear → transthoracic echocardiography,
transesophageal echo, lumbar puncture, Gallium 67 scan, X ray or CT
on the nasal sinuses
5- Malignancies
- Hematologic → hematologic peripheral smear, serum protein
electrophoreses → if diagnosis not clear → bone marrow biopsy
- Non-hematologic → mammography, chest CT with contrast, upper
endoscopy, colonoscopy, bone scan, gallium 67 scan → if diagnosis not
clear → MRI brain, diagnostic laparoscopy, liver biopsy, biopsy of
suspicious skin lesion or lymph node
6- Autoimmune conditions
- RF, ANA → if diagnosis not clear → temporal artery biopsy, lymph
node biopsy
7- Miscellaneous
- Order appropriate diagnostic tests based on informations from the
history

95
Other infections of the liver

Bacterial infections
1- Legionella pneumophila
2- S.aureus (TSS)
3- Clostridium perfringens
4- Listeria monocytogenes
5- Nisseria gonorrhoeae
6- Burkholderia pseudomallei (melioidosis)
7- Shigella and salmonella spp.
8- Yersinia enterocolitica
9- Coxiella burnetii (Q fever)
10- Rickettsia rickettsii (Rocky mountain spotted fever)
11- Actinomyces israelii (actinomycosis)
12- Bartonella bacilliformis (bartonellosis)
13- Brucella spp.

Spirochetal infections of the liver [see related topics]

1- Leptospirosis ®
2- Syphilis ®
3- Lyme disease ®
4- Relapsing fever ®

Parasitic infections [see tables in Lawrence's p. 386]

1- Protozoal infections
- Amoebic liver abscess ® ‫مهم‬
- Malaria & Babesiosis
- Leishmaniasis (Kala-Azar)
- Toxoplasmosis
2- Trematoda
- Schistosomiasis
- Fascioliasis
- Clonorchiasis & opisthorchiasis
3- Cestoda
- E.granulosus (hydatd cyst)
- E.multilocularis (alveolar cyst)
4- Nematoda
- Ascariasis
- VLM (toxocariasis)
96
 - Capillaria hepatica
- Strongyloids
- Trichinella spiralis
Bacterial infections → picture of acute hepatitis
1- Legionella pneumophila
- Pneumona , abnotmal liver functions usually without jaundice
- Liver histology → non specific
- Treatment → fluoroquinolones or macrolide antibiotics
2- S.aureus (TSS)
- Fever, scarlatiniform rash, vomiting, diarrhea, hypotension and
multiorgan failure
- Deep jaundice and high serum aminotransferases
- Liver histology → necrosis, steatosis, cholestasis
- Diagnosis confirmed by culture of toxigenic S.aureus or detection of
TSST-1
- Treatment
 Methicillin sensitive → IV clindamycin + nafcillin
 Methicillin resistant → vancomycin or linezolid
3- Clostridium perfringens
- Local wound pain, abdominal pain, diarrhea, myonecrosis or gas
gangrene
- Jaundice in 20% of cases [due to massive intravascular hemolysis]
- Liver abscess formation and gas in the portal vein
- Treatment → IV penicillin and clindamycin
4- Listeria monocytogenes
- Meningoencephalitis and pneumonitis commonly in neonates,
immunosuppressed
- Liver involvement rare in adults → single or multiple microabscesses or
granulomatous hepatitis
- Liver enzymes typically very high

97
 - Treatment → abscess drainage + combination of ampicillin and
aminoglycosides for 3-4 weeks

5- Nisseria gonorrhoeae
- 50% of disseminated infection → ↑ ALP, AST, jaundice uncommon
- Fitz-Hugh-Curtis syndrome (perihepatitis) is a common complication
almost in women
- Sudden onset of sharp right upper quadrant pain, often following lower
abdominal pain is an indicator of long standing PID → distinguished
from gonococcal bacteremia by characteristic friction rub over the liver
and negative blood cultures
- Diagnosis → vaginal cultures for N.gonorrhoae & laparoscopy may
show characteristic "violin string" adhesions between the liver capsule
and the anterior abdominal wall
- Treatment → IV ceftriaxone
6- Burkholderia pseudomallei (melioidosis)
- Acute disease → hepatomegally, jaundice, lung and GIT affection
- Chronic disease → granulomas with central necrosis
- Diagnosis → indirect hemagglutination assay
- Treatment → IV ceftazidime, imipenem or meropenem
7- Shigella ans salmonella spp.
- Shigella → cholestatic hepatitis
- Typhoid fever → acute hepatitis with fever and tender hepatomegally,
cholangitis, cholecystitis and liver abscess may occur → mild to
moderate ↑ in bilirubin and aminotransferases
- Treatment → fluoroquinolones, 3rd generation cephalosporins or
ampicillin
8- Yersinia enterocolitica
- Ileocolitis in children & terminal ileitis and mesenteric adenitis in adults

98
 - Patients with liver involvement have underlying comorbidities as DM,
cirrhosis or hempchromatosis
- Multiple abscesses in liver and spleen or noncaseating granulomas

9- Coxiella burnetii (Q fever)

- Relapsing fevers, headache, myalgias, malaise, pnemonitis and culture
negative endocarditis
- Liver commonly affected → elevated ALP
- Liver histology → fibrin ring granuloma
- Diagnosis → complement fixation test
- Treatment → doxycycline
10- Rickettsia rickettsii (Rocky mountain spotted fever)
- Multiorgan failure → liver affection → jaundice
- Liver histology → portal perivascular inflammation and vasculitis
- Treatment → tetracycline
11- Actinomyces israelli
- Cervicofacial infection is the most common followed by GIT
involvement
- Hepatic abscesses in 15% of cases of abdominal actinomycosis
- Diagnosis → aspiration of the abscess [characteristic sulfur granules or
positive anaerobic culture]
- Treatment → prolonged course of IV penicillin or oral tetracycline
12- Bartonella bacilliformis
- Jaundice, hemolysis, HSM and lymphadenopathy
- Histology → centrilobular necrosis and splenic infarction may occur
- Treatment → chloramphenicol, fluoroquinolones or tetracycline
13- Brucella spp.
- Prolonged fever, bony aches, sweating, headache, acute or chronic
disease
- Hepatomegally and abnormal biochemical tests are common
- Histology → multiple noncaseating granulomas
99
 - Diagnosis → slide agglutination test, blood culture, imaging → lesions
with central calcification and a necrotic rim
- Treatment → combination of streptomycin (3 weeks) + rifampicin and
doxycycline for 3 months or more

Diarrhea caused by protozoa other than amoebic

Causes
1- E.histolytica
2- Giardia lamblia → ®
3- Balantidium coli
4- Cryptosporidium spp.
5- Cyclospora
6- Isospora belli
7- Microsporidia

Balantidium coli

Pathogenesis
1- Infective stage → cyst
2- Source → pig
3- Habitat → large intestine
4- Mode of infection
- Ingestion of the cyst with food or drink contaminated with pig feces
- Autoinfection
5- Sites → cecum and rectosigmoid [flask shaped ulcers with undermined edge]
and rarely extraintestinal
Clinical features
1- Diarrhea → acute cases (caecum)
2- Dysentery → chronic cases (rectosigmoid)

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 3- Complications → hge, perforation, peritonitis, 2ry foci and 2ry bacterial
infections
Diagnosis → stool examination for trophozoites (loose stool) or cyst (formed stool)

Treatment
1- Metronidazole → 750 mg 3 times daily for 5 days
2- Tetracycline 500 mg 4 times daily for 10 days
3- Tinidazole 2 g single dose

Cryptosporidium parvum

Pathogenesis
1- Infective stage → sporulated oocysts (4 sporozoites)
2- Source → man and domestic animals
3- Habitat → small intestine
4- Mode of infection → contaminated food & drink and autoinfection
5- There is partial atrophy of the intestinal villi with cellular infiltration
Clinical features
1- In immunocompetent patients
- Mild self limited diarrhea lasting for 2 weeks
- In some cases, esp. in children associated with abdominal cramps, low
grade fever, anorexia and loss of weight
2- In immunocompromized patients
- Severe, prolonged and may be fatal esp. in AIDS (opportunistic
infection)
- Severe diarrhea, dehydration, malabsorption or dissemination of the
parasites to other organs (esophaguem gall bladder, urinary bladder,
respiratory tract) may occur
Investigations
1- Stool smear stained with modified Z.N stain → -ve
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 2- Concentration methods → -ve (very small organism)
3- Direct fluorescent antibody test → detect oocysts antigens in stools
4- Intestinal biopsy → detect meronts and gamonts

Treatment
1- Supportive → fluid and electrolyte replacement
2- Paromomycin
- 500 mg 3-4 times daily for 2 weeks followed by 1 gm twice daily for 1
month followed by a maintenance dose of 500 mg twice daily [to
prevent relapse]
- Treatment difficult because available drugs don't eradicate the infection
(only cause suppression)
3- Spiramycin → 3 gm /day in divided doses for 2-4 weeks

Cyclospora spp.

Pathogenesis
1- Infective stage → sporulated oocyst
2- Habitat → small intestine
3- Mode of infection → contamination esp. water and autoinfection
4- Villous atrophy and crypt hyperplasia
Clinical features
1- Immunocompetent → relapsing or cyclic watery diarrhea, associated with
nausea, vomiting, flatulence and abdominal cramps [may be weight loss, low
grade fever, fatigue, anorexia]
2- Immunocompromized → severe prolonged course, may be biliary affection
Investigations
1- Stool examination → smear examined fresh unstained or stained with acid fast
stain to show oocysts
2- Jejuna biopsy → detect asexual stages
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Treatment → Trimethoprim 160 mg + Sulphamethoxazole 800 mg twice daily for 7
days

Isospora belli

Pathogenesis → as before (but only epithelium is affected)

Clinical features → as cryptosporidium (+ chronic diarrhea may occur in
immunocompetent)
Investigations → stool analysis for oocysts + no biopsy
Treatment → combination of Trimethoprim 160 mg + Sulphamethoxazole 800 mg
every 6 hours for 10 days followed by the same dosage twice daily for 3 weeks

Microsporidia

Pathogenesis
1- Infective stage → spores (sporoplasm)
2- Mode of infection
- Mostly by ingestion
- Inhalation
- Ocular exposure and sexual intercourse
Clinical features
1- Intestinal microsporidiosis
- The most common form and usually seen in AIDS
- Prolonged diarrhea, dehydration, malabsorption
- Cholangitis and rhinosinusitis and spread to multiple organs may occur
2- Ocular microsporidiosis
- Conjunctivitis, keratitis and corneal ulcers
3- Microsporidial myositis

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 - Generalized muscle weakness, myalgia, fever and weight loss
4- Systemic infection
- Hepatic, renal, respiratory, ….

Investigations
1- Biopsy → detection of organisms in stained biopsy material
2- Examination of excreta and body fluids → identification of stained spores in
feces, urine, bile and duodenal, bronchial or nasal fluids
3- Electron microscopy → identify the ultra structure of the parasite
4- Molecular assays
Treatment
1- Albendazole
- 400 mg 3 times /day for 2 weeks
- Used for intestinal and disseminated infections
2- Topical fumagillin → for ocular lesions

Pneumocysts carinii

Pathogenesis
1- Infective stage → cyst
2- Habitat → alveoli of the lung
3- Mode of infection → air-borne and by direct or close contact
4- Pathology
- Usually affect both lungs
- The alveoli are filled with hyaline foamy eosinophilic exudates with
characteristic honeycomb form
- In disseminated infection, granulomatous lesions develop in various
organs
Clinical features
1- Asymptomatic latent infection → in immunocompetent host
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 2- Infantile interstitial plasma cell pneumonia
- Usually affects malnourished premature infants
- Dyspnea and cyanosis and the infant may die if not treated
3- Pneumocytosis in the immunocompromized patient
- Severe manifestations in the form of dyspnea, fever and non-productive
cough
4- Extrapulmonary lesions
- As spleen, liver, bone marrow, GIT and urinary tracts (in patients with
AIDS)
Diagnosis
1- Clinical → pneumonia in immunodeficient patient
2- X ray → diffuse ground glass appearance
3- Microscopy
- Detection of organisms in bronchoalveolar lavage specimens by silver
or fluorescent stains (organisms usually not found in sputum)
- Biopsy of the lung → characteristic hyaline eosinophilic exudates with
the honeycomb structure and stained organisms
4- Serology → of limited value in immunocompromized patients
5- Molecular assay → esp. helpful in immunocompromized patients
Treatment
1- Co-trimoxazole in high dose
- Sulfamethoxazole 100 mg/kg/ day + Trimethoprim 20 mg/kg/day in 2-4
divided doses orally or IV
2- Symptomatic treatment → oxygen, bronchodilators

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Acute flaccid paralysis

Definition
1- Weakness in one or more limbs or the respiratory or bulbar muscles resulting
from damage to lower motor neurons
2- Classically there is weakness with
- Reduced tone (flaccid)
- Reduced or absent reflexes
3- Acute spinal shock e.g. by trauma (UMNL) can cause initially flaccid paralysis
before spasticity develops
Causes
1- Poliomyelitis. [AHc damage]
- Presentations
 Asymptomatic to mild non-specific febrile illness
 Viral meningitis
 Paralytic poliomyelitis → spinal or bulbar
- Paralytic poliomyelitis
 Biphasic → non specific fever followed by a brief afebrile period
before the CNS is invaded
 This is heralded by further fever and an acute onset asymmetrical
flaccid paralysis of one or more limbs which may be painful
2- Enterovirus 71. [AHc]
- Cause epidemics in recent years esp. in Asia , often in association with
hand, foot and mouth disease
- Large outbreaks occur in some countries every 3-4 years
3- Japanese encephalitis & West Nile viruses. [AHc]
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 - Typically cause meningoencephalitis
- Other flaviviruses can also present with a pure flaccid paralysis
clinically similar to polio
4- Echovirus, coxackie virus [AHc]
5- Guillain-Barre syndrome [immune mediated – damage to myelin]
- Acute inflammatory demyelinating polyneuropathy typically presenting
weeks after a febrile illness
- Back pain then symmetrical ascending flaccid paralysis and sensory
changes. Recovery is usual.
- Treat rapidly progressing symptoms with intravenous immunoglobulin
if available.

6- Chinese paralytic syndrome: [immune mediated – damage to motor axons]

- Acute motor & axonal neuropathy “AMAN” typically follows diarrhea
caused by Campylobacter jejuni.
- Symmetrical weakness is present with no sensory changes.
- Residual weakness is common
- It occurs in summer epidemics in China.
7- Other causes
- Paralytic rabies.
- Botulinum toxin.
- Diphtheritic neuropathy
 History of a severe sore throat with neck swelling
- Tick paralysis
 A slowly ascending paralysis that recovers when the tick is
removed
- Exposure to toxins

Nerve conduction studies

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 1- Anterior horn cell damage → motor amplitude is reduced because motor cell
bodies have been damaged.
2- Classical Guillain - Barre’ syndrome → motor and sensory nerves have
reduced conduction velocities and delayed distal latencies because demyelinated
nerves conduct more slowly.
3- Chinese paralytic syndrome → motor amplitudes are reduced because motor
axons have been damaged.
Clinical features to distinguish causes
Direct viral damage to anterior Immune mediated damage to
horn cells of the spinal cord e.g. peripheral nerves (motor, and often
polio sensory) e.g. GB syndrome
Paralysis onset During (or straight after) febrile Several weeks after illness
illness
Pattern of paralysis Asymmetrical Symmetrical
Time of max. Short (e.g. 2-3 days) Long (e.g. 7-14 days)
weakness
Sensory involvement No Often (depending on exact disease)
CSF ↑ lymphocytes (e.g. 100/mm3) ↑ protein (e.g. 100 mg/dl esp. late)
Pain Often limb muscle pain Often back pain

Descending paralysis

Causes
1- Botulism
2- Diphtheria
3- Miller-Fisher variant of GB syndrome
- The disease starts at the eyes and moves down with risk of respiratory
paralysis
- Blood test is diagnostic but delayed results (3-5 days)
- Spinal tap unreliable but aid in early management

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Spastic paralysis

Definition
1- Spastic paralysis is caused by damage to the upper motor neurones
2- Characterized by weakness with increased tone, brisk reflexes and extensor
plantars.

Causes
1- Cortical
- Cerebral palsy (spastic diplegia)
- Cerebrovascular accidents
- Parasaggital meningioma and other tumors
- Other space occupying lesions
2- Extrinsic [usually painful]  degenerative
- Cervical spondylosis
- Trauma
- Disc herniation
3- Intrinsic [usually painless]  diffuse
- Multiple sclerosis
- Acute disseminated encephalomyelitis
4- Spinal
- Transverse myelitis
- Subacute combined degeneration of the spinal cord
- Tropical spastic paraparesis
- HIV myelopathy
- Syringomyelia
- Vascular (infarct, AV malformation)
5- Spinal space occupying lesions [often with painful radiculopathy]
- Tuberculosis
- Tumors
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 - Spinal epidural abscess
- Paravertebral abscess
- Schistosomiasis and other parasites
Important Causes
1- Tuberculosis
- TB causes spastic paralysis in one of the following three ways:
 Pott's disease → vertebral collapse and secondary cord
compression (a bony prominent sharp kyphosis caused by a
collapsed vertebra is known as a gibbus)
 Chronic TB meningitis → 2ry arteritis and cord infarction
 A tuberculoma → compresses the cord directly
- History of TB elsewhere
- Investigations → tuberculin test, ESR, chest X ray, spinal X ray, CT or
MRI, CSF analysis
- Antituberculous drugs + surgery if appropriate
2- HIV myelopathy:
- Cause
 Direct HIV-1 invasion
 Lymphoma, Cryptococcus and herpes viruses
- Frequent finding in patients with AIDS-dementia complex
- Features
 Spasticity with increased or decreased reflexes
 Ataxia
 Incontinence and dorsal column signs
 MRI usually normal
3- Tropical spastic paraparesis:
- It’s found in equatorial Africa, South America, Caribbean, and Japan.
- Cause → HTLV-1, transmitted sexually, by exposure to blood products
or by breast milk.
- Features

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  Progressive spastic paraparesis
 Impaired vibration and joint position sensation
 Bowel and bladder dysfunction
4- Subacute combined degeneration of spinal cord [Vitamin B12↓]:
- Causes
 Poor diet
 Impaired absorption → tropical sprue, D. latum, GIT surgery
 Pernicious anemia
- Deficits → mixture of
 Upper motor neurone deficit (corticospinal tract damage)
 Sensory deficit (dorsal column involvement and peripheral
neuropathy)
 Sometimes, optic neuropathy and dementia
- Features
 Extensor plantars with absent knee jerks
 Lhermitte's sign → neck flexion causes shooting pains down the
arms
 Macrocytic anemia
- Treatment → IM vitamin B12 (hydroxycobalamin) injections 1 mg/day
for 6 days then reducing to a maintenance dose [1 mg every 3 months ]
for life unless the cause of deficiency has been eliminated
5- Spinal epidural abscess
- Cause → S. aureus
- Features
 Triad of fever + backache/tenderness + radicular pain
 Followed by rapidly progressive spastic paraparesis
 Sensory loss
 Bowel and bladder dysfunction
- Investigations
 ↑ ESR, TLC

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  CSF → mild pleocytosis with ↑ protein level
 X ray → soft tissue changes and associated vertebral
osteomyelitis
 Myelography → block to the flow of contrast medium
 MRI is the investigation of choice
- Treatment
 Emergency surgical drainage
 Vancomycin or nafcillin antibiotics
6- Transverse myelitis:
- Acute inflammation of the spinal cord
- Causes
 No cause in many patients
 Viral  HIV, Dengue.
 Bacterial  Mycoplasma pneumonia.
 Spirocetal  Borrelia burgdorferi, leptospirosis, syphilis.
 Rickettsial  scrub typhus.
 Parasitic  schistosomiasis
 Post most vaccinations
 Connective tissue disorders
- Features
 Rapid presentation
 Often sensory level is present
 Monophasic illness in many patients but some will develop
multiple sclerosis or Devic's neuromyelitis optica
Assessment of patient with spastic paralysis
1- Speed of onset
- Rapid in vascular disease
- More prolonged in inflammatory, infectious and compressive disease.
2- Past and current medical problems
- Cerebral palsy, tuberculosis, HIV, macrocytic anaemia.

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 3- Urinary hesitancy, frequency or retention (the latter is a late feature)
4- Constipation, incontinence, reduced anal tone and sensation
5- Presence of pain
- Extrinsic lesions compressing spinal roots cause radicular pain (e.g.
tumors)
- Abscesses give back pain and local tenderness.
6- Examine for a gibbus of Pott’s disease
7- Examine for naevus / hairy patch of spinal dysraphism (spina bifida occulta)
8- Sensory level ‫ــــــــ‬nipples are T4, umbilicus is T10
Clues to the site of damage of UMN
1- A pure spastic paraparesis with no sensory changes
- Usually caused by damage in the brain where sensory and motor
pathways are far apart (e.g. spastic diplegia in cerebral palsy, or frontal
meningioma).
2- In the spinal cord, sensory pathways lie close to the motor pathways and so are
often also affected by any pathology.
- Look for dorsal column signs (Loss of light touch, vibration and joint
position sensation) and a sensory level.
3- Intrinsic cord lesions → usually painless.
4- Extrinsic lesions
- Which causing spinal cord compression often also press on the sensory
roots as they leave the spinal cord
- Thus cause pain in the distribution of those roots (radicular pain).

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Botulism

Causative agent → clostridium botulinum

Pathogenesis → neurotoxin in food blocks release of acetylcholine at motor end
plate  descending flaccid paralysis
Mode of infection
1- Ingestion of canned alkaline food or preserved fish
2- Spores germinate under anaerobic conditions → vegetative forms → grow and
produce toxin [the toxin is destroyed by heating for 20 min at 100 C
Clinical features
1- I.P. → 12-36 hours
2- Vomiting initially but No other GIT symptoms

3- Then neurological manifestations

- Diplopia (paresis of ocular muscles)
- Dysphagia (paresis of pharyngeal muscles)
- Dyspnea (paresis respiratory muscles)
- Dysphonia (paresis of laryngeal muscles)
- Paresis of skeletal muscles
Diagnosis  toxin demonstration in stool, vomitus, food remnants and rarely in
blood
Treatment
1- Clear airway, ventilation
2- Gastric wash
3- Trivalent antitoxin
- 20 ml IV followed by 10 ml 2-4 hours then every 12-24 hours as
necessary
4- Guanidine HCL
- 15-40 mg/kg
- It improves the paralysis by reversing the neuromuscular block
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Guillain Barre syndrome

Definition
1- It is an inflammation of the peripheral nerve and roots with demyelination
2- Due to immune or post viral insult (1-4 wks after)
Clinical features
1- Initial febrile illness → fever, headache and malaise
2- Latent period for days or weeks
3- Then paralytic stage [ascending paralyasis]
- All muscles of the limbs are affected
- Proximal >distal
- Starts in LL and ascend to involve UL , trunk and muscles of respiration
- Sensory → mild glove and stock hypothesia
- Cranial nerves → 3,7,10 [esp. bilateral facial nerves]
Investigations
1- CSF  cytoalbuminous dissociation due to root affection  accurate in 90% of
cases if done after 1 week of onset of symptoms (↑ protein with either normal
or moderately increased cell count)
2- Nerve conduction studies and EMG
3- Serum lead and urinary porphyrin → to exclude porphyria
Treatment
1- Rest (guard against DVT)
2- Care of muscles of respiration
3- Plasmapheresis  of choice
4- IV immunoglobulins with the first 2 week
5- Steroids → 20 mg prednisolone tid (minimal or no rolr)
6- Physiotherapy
Prognosis  complete recovery in 80% of cases within 3-6 months and the
remainder suffer residual defecit (mortality 10%)
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Diphtheria

Causative organism  gram +ve pleomorphic rod Corynebacterium diphtheria

Mode of infection
1- Direct → droplet infection from cases or carriers
2- Indirect → contaminated fomites
Pathogenesis → the organism remains localized at the site of infection with
absorption of a soluble exotoxin which damage heart and nervous system
Incupation period → 2-7 days

Clinical features
1- Pharyngeal diphtheria
- Severe prostration, constitutional symptoms and low grade fever
- High fever if complicated by infection with other bacteria
- Grayish membrane (necrosed epithelial cells, fibrin, inflammatory cells
and RBCs) with pharyngeal and tonsillar inflammation
- The membrane bleeds easily if scraped
- Bull neck (cervical lymphadenopathy in severe cases)
2- Laryngeal diphtheria
- Husky voive, brassy cough with danger of respiratory obstruction
3- Nasal and cutaneous diphtheria → rare forms
Diagnosis
1- Clinical as therapy is urgent
2- Culture of a portion of membrane on Loffler's medium or blood tellurite
3- Shick test  detects the immune status of the patient [intradermal injection of
toxin → absence of reaction means immunity]
Complications

116
 1- Respiratory
- Laryngeal obstruction due to extension of the membrane and edema of
respiratory mucosa
- Lung collapse due to inhalation of a piece of the membrane
- Bronchopneumonia due to 2ry infection
- Death from respiratory failure may occur
2- Cardiovascular
- Myocarditis
- Arrhythmia
- Heart failure
3- Paralytic
- Palato- pharyngeal paralysis  usually in the 2nd week with nasal voice,
dysphagia and nasal regurgitation
- Ocular paralysis
 Diplopia (6th nerve paralysis)
 Loss of accommodation (3rd nerve paralysis)
 Peripheral polyneuritis
4- Renal → toxic nephritis
5- Cutaneous → purpuric skin eruption in malignant cases
Treatment
1- Prophylaxis
- Active immunization to all children (DPT)
- Contacts should receive erythromycin and toxoid immunization
2- General measures
- Bed rest, isolation, IV fluids and observation
3- Specific treatment
- Antitoxin
 Dose : 20000-100000 unit IM
 To be given early (once clinical diagnosis) to prevent further
fixation of toxin to tissue receptors

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 - Antibiotics
 Erythromycin or penicillin G
 They are given till 3 consecutive throat swabs are negative
- Toxoid
 After recovery full course of immunization should be given
4- Treatment of complications

Transverse myelitis

Clinical features
1- Acute onset of fever + paraplegia
2- The course is usually regressive
3- At the level of the lesion
- Sensory  loss of sensation at the level of the lesion e.g. at the level of
umbilicus if the level of the lesion at T 10
- Motor (LMNL)  in the muscles supplied by the affected segment so,
there are weakness, flaccidity and hyporeflexia in these muscles
4- Below the level of the lesion
- Sensory  loss of all sensation (pain, temp., touch and deep) due to
affection of the spinothalamic tract and posterior column tracts
- Motor  UMNL
 Acute stage (shock or flaccid stage) → hypotonia and
hyporeflexia
 After flaccid stage → spasticity, hyperreflexia and extensor
planter
- Sphincteric disturbance
 Early → retention with overflow
 Late → autonomic bladder
- Autonomic manifestations below the lesion
Investigations
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 1- No gross abnormality
2- Important to exclude compression by CT, MRI
3- Exclude multiple sclerosis by MRI brain
4- MRI may be normal or may shows swollen spinal segments in the affected
region. Gadolinium enhancement may occur
5- CSF → increased cells and proteins

Treatment
1- Steroids
- IV methyl prednisolone is preferred
- Prednisolone 20 mg tid then gradual tapering with improvement
2- ACTH can be used
3- Physiotherapy and general care of paraplegic limb

Poliomyeilitis

Causative agent → polionirus (Enterovirus) – 3 antigenically distinct types

Mode of infection  feco-oral
Pathogenesis
1- The 1ry site of multiplication are the oropharynx and cetain parts of the
intestine → the virus proceed to the regional lymph nodes and blood stream
2- Then to CNS esp. the anterior horn cells of the spinal cord → flaccid paralysis
Clinical features
1- I.P. → 8-20 days
2- Inapparent infection
- In 95% of cases
- No clinical manifestations
- The virus can be recovered from oropharynx and/or stools and type
specific antibodies are detected in the serum
3- Abortive illness
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 - Flu like symptoms, myalgia, upper respiratory illness and/or GIT with
no nervous manifestations
4- Non-paralytic poliomyelitis
- Fever, sore throat, severe headache and stiffness of the neck, back and
legs
- CSF shows high protein content and pleocytosis

5- Paralytic poliomyelitis
- In minority of cases
- Weakness which may be associated with pain and tenderness in the
extremities followed by paralysis
- Paralysis is common in the spinal cord assuming spotty or asymmetrical
distribution
- Groups of muscles in the arms or legs are affected
- Bulbar paralysis rarely occurs
Diagnosis
1- Stool culture
2- Four fold rise of neutralizing antibody titre in the sera of the patient in the acute
and convalescent stages of the disease is essential for diagnosis
Treatment → symptomatic according to the case
Prophylaxis
1- Salk vaccine
- Formalin killed tissue culture vaccine
- 2 doses each 1 ml IM at an interval of 3 weeks
2- Sabin vaccine
- Live attenuated
- Given orally on 3 doses at an interval of 2 months
- Easy to administer and can be used in mass campaigns
- Provides both local and systemic humoral immunity

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 Viral hemorrhagic fevers

Rift valley fever

Pathogenesis
1- Causative organism → rift valley fever virus [arbovirus, bunyaviridae]
- Vital stain reveals plaque assay (one virus) with 4 sized variants
2- Mode of transmission → bite of culex pipiens, anopheles pharoensis and
airborne infection
3- Distribution
- Endemic in kenea
- In Egypt → 18,000 cases and 598 deaths in 1977 & 195 cases in 1978 &
163 cases in 1979 & sporadic cases in 1980 → the diseases recurred on
1993 in Kom Ombo and Aswan in the form of a small outbreak
Clinical features [4 presentations]
1- There are 4 clinical presentations
- Influenza-like or Dengue like fever
- Hemorrhagic form as vasculitis and hge in the GIT
- Encephalitis
- Ocular manifestations
2- Influenza like or dengue like fever in most cases
- Sudden onset of frontal headache, biphasic type of fever, retrobulbar
pain, myalgia and generalized body aches
- May be cough, nausea, vomiting or diarrhea
- Examination
 Conjunctival injection as a constant findings
 Some may be drowsy
 May be petechial hemorrhages
 Chest usually clear

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  Liver may be enlarged
3- Ocular manifestations
- Usually occur in
 Old poor people
 Those with repeated and prolonged episodes of fever
 Those with HSM
 Those with DM
- Lesions
 Retinal lesions in the form of macular and paramacular exudates,
extramacular hemorrhages and exudates, retinal vasculitis and
choroiditis
 Choroidal lesions in the form of choroidal vasculitis and
choroiditis
 Uveitis, anterior or posterior
- Fluorescein angiography can differentiate eye lesions
- Most cases have bilateral lesions
- If the macula is affected, it will cause permanent blindness
4- Rare cases may present as encephalitis
5- Fatal cases [hemorrhagic form]
- Jaundice
- Severe bleeding → epistaxis, hemoptysis, hematemesis, melena and
vaginal bleeding
- Acute massive liver necrosis, splenic congestion and he, heart affection

Investigations
1- Criteria of hemorrhagic fever
2- Blood samples and nasopharyngeal washings
- Taken for virus studies at the time of initial examination and at
convalescence
3- Haemagglutination inhibition antibody titre of 1: 160 or better 4 fold rise

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 4- CFT
5- Plaque reduction test  highly specific
6- CBC  slight leucopenia with relative lymphocytosis and thrombocytopenia
7- Liver function tests may be impaired
Treatment and prevention
1- Non specific therapy
- Ribaverin
- Gamma globulins
- Antipyretics, antibiotics and steroids
2- Vaccine
- Human vaccine  inactivated formalin chick embryo, one injection
weekly for 3 weeks gives immunity for 6-12 months
- Animal vaccine → either live attenuated or formalin killed
3- Antimosquito measures are essential for control of the disease

Lassa fever

Pathogenesis
1- Causative agent → Arena virus
2- Mode of infection
- Transmission from rodent to rodent and from rodent to man by
 Direct contact with virus shed by the animal esp. in urine, on food
stuffs
 Nosocomial infection may occur
3- Distribution
- First discovered in 1969, in Lassa in Nigeria → cause death of 2 nurses
and a grave illness in the 3rd
4- Pathology  generalized capillary damage with increased permeability, organs
affected include liver (subcapsular hge, eosinophilic necrosis, eosinophilic

123
 bodies in the sinusoids), spleen (lymphocytic infiltration), intestine (edema and
hge), myocardium (edema and hge), lung (focal pneumonitis)
Clinical features
1- Incubation period → about 1 week
2- Spectrum ranging from asymptomatic to mild disease up to fatal pansystemic
disease
3- High fever, headache and tinnitus
4- Vomiting, diarrhea and epigastric pain
5- Severe pharyngitis with white patches on the pharynx, soft palate and tonsillar
pillars
6- Cervical lymphadenopathy
7- Dry or productive cough
8- Bleeding tendencies and rashes
9- Pleural effusion
10- Myocarditis , hypotension and shock
11- Protenuria and renal failure
Differential diagnosis
1- Other hemorrhagic fevers
2- Typhus fevers
3- Leptospirosis
Investigations
1- Demonstration of antibodies and rising titres by CFT and neutralization test
2- In early stages  moderate leucopenia with an increase of immature
neutrophilic elements. May be thrombocytopenia

Treatment
1- No specific therapy
2- Symptomatic treatment

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Dengue fever

Pathogenesis
1- Causative agent → dengue fever virus (group B arboviruses)
2- Mode of infection → bite of Aedes Egypti
3- Prevalent in far east Asia, America and west Africa
Clinical features
1- Fever either continuous or biphasic
2- Headache, backache and retro-orbital pain, photophobia
3- Pains in the muscles, joints (arthralgia) and eyes
4- Generalized lymphadenopathy
5- Macular rash
6- 1/3 of cases have +ve tourniquet test (a blood pressure cuff inflated to half way
between systolic and diastolic pressure for 5 min produces 20 or more petechiae
in a 2.5 cm2 area on the forearm)
7- Dengue hemorrhagic fever
- Reported only in far east
- Usually seen in patients with previous attacks of dengue fever
- Most common in pre-teenage children
- Clinically
 Sudden onset of fever, vomiting, abdominal pain and headache
 Usually followed by bleeding from nose, gums, GIT and injection
sites
 Thrombocytopenia and haemoconcentration are present
8- Dengue shock syndrome
- Characterized in addition by hypotension and shock with case fatality
rate of 50%
Investigations → Haemagglutination and CFT esp. with 4 fold rise of titres
Treatment → non specific therapy

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Yellow fever

Pathogenesis & types

1- Causative agent → yellow fever virus (arbovirus)
2- Types
- Urban yellow fever → affecting humans and transmitted by Aedes
Egypti which requires a blood meal for deposition of ova
- Jungle yellow fever → affecting monkeys
3- Distribution → Africa and south America
4- Pathology  after the bite, the virus spreads to local lymph nodes with
multiplication → then after I.P. it invades the blood stream → reaches the liver,
spleen, kidneys, stomach and bone marrow initiating necrotic processes and
hemorrhages
Clinical features
Main symptoms
1- I.P.  3-6 days
2- Fever, headache, retro-orbital pain, photophobia, generalized body aches,
myalgia and severe prostration
3- Nausea, vomiting which may be coffee-ground in appearance
4- Jaundice
5- Fulminant hepatic failure
6- Bleeding either SC or from the nose, GIT or urinary bladder
7- Oliguria, hiccough and renal failure
8- Delirium
Main signs
1- Fever, erythematous rash, conjunctival injection and tachycardia
2- Fever drops on the 3rd day of the disease to recur again with jaundice,
bradycardia, hypotension and bleeding
3- Fever usually drops by the 7th or 8th day of the disease

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 4- Faget's sign  is the failure of the heart rate to increase with a rising
temperature and is indicative of cardiac damage
Investigations
1- Leucopenia, thrombocytopenia and clotting abnormalities
2- Bilirubinemia and biliruubinuria and elevated liver enzymes
3- Proteinuria disappears completely after recovery
4- Detection of antibodies in the serum from the 2nd week of the disease
5- Liver histology → Councilman bodies (occur also in rift valley fever and
Crimean-Congo hemorrhagic fever)
Differential diagnosis
1- Viral hepatitis
2- Leptospirosis
3- EBV. CMV
4- Malignant malaria
Prognosis
1- Bad prognostic signs are
- Copious black vomitus
- Melena
- Hiccough
- Anuria
2- Mortality high in severe cases (usually on 6th-10th day)
Treatment
1- High CHO and high protein liquid diet
2- IV fluids
3- Symptomatic therapy
Prevention
1- Mosquito control to prevent transmission
2- 17-D vaccine
- Live attenuated virus vaccine (17 D strain)
- Highly effective given to persons travelling to endemic areas
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 - Single 0.5 cc SC injection
- Immunity lasts for about 10 years
- Recent reports of adverse effects esp. in elderly

Marburg virus disease

Discovery and transmission

1- 1st recognized in 1967 when 31 persons became ill in Germany and Yugoslavia
mostly after exposure to organs or body fluids of vervet monkeys imported from
ugansa for the production of tissue culture material
2- Way of spread from reservoir to man is unknown, but the disease is sexually
transmitted from the patient to his wife through semen
Clinical features
1- Sudden onset with fever, headache, myalgia and malaise
2- Followed by nausea, vomiting and profuse watery diarrhea
3- Frequent complaint is  throat discomfort
4- Erythematous maculopapular rash appears on day 4-6 and lasts for few daus
and followed by marked desquamation of the skin
5- Dry cough and chest pain are common
6- Uveitis and orchitis may occur
7- Bleeding is a common complication in the form of epistaxis, GIT bleeding,
hemoptysis and hematuria and may be the cause of death
8- Also myocarditis and hepatic damage may cause death
9-
Ebola virus disease

Discovery
1- 1st recognized in 1976 when a large outbreak involving 300 people occurred in
southern Sudan and northern Zair
2- It is the most lethal of viral hemorrhagic fevers currently known
Clinical features  clinically indistinguishable from Marburg virus disease
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 Approach to jaundice

Definition
1- Yellow discoloration of skin, sclera and mucous membranes caused by accumulation
of bilirubin, a by-product of heme metabolism
2- Total serum bilirubin > 1.5 mg/dl but typically jaundice become apparent when
bilirubin reaches 2.5-3 mg/dl [normal total bilirubin 1-1.5 with conjugated < 0.3
mg/dl)
Classification
1- According to the site of defect in bilirubin pathway
- Prehepatic → overproduction of bilirubin
- Intrahepatic → defect in bilirubin transport, conjugation or excretion
- Posthepatic → biliary obstruction
2- According to the predominant type of bilirubin
- Unconjugated → bilirubin overproduction, impaired hepatic bilirubin uptake,
impaired conjugation of bilirubin,
- Conjugated → decreased bilirubin excretion, hepatocyte dysfunction or
biliary obstruction
- Mixed → seen in hepatocellular disease, biliary obstruction and decreased
canalicular excretion

Causes
Unconjugated hyperbilirubinemia
1- Bilirubin overproduction
- Hemolysis & ineffective erythropoiesis
 Sickle cell anemia
 Thalassemia
 G6PD ↓
 Pyruvate kinase ↓
 Malaria
 ABO incompatibility
 Lead toxicity
- Resorption of large hematomas

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 2- Impaired hepatic bilirubin uptake
- ↓ hepatic blood flow
 Cirrhosis
 Portocaval shunts
 Congestive heart failure
- Drugs
 Rifampicin
 Probenecid
 Sulfonamides
 Aspirin
 NSAIDs
 Contrast dye
3- Impaired conjugation of bilirubin
- Gilbert's syndrome
- Crigler-Najjar syndrome
- Neonatal jaundice
 Physiological
 Breast milk jaundice
 Hypothyroidism
 Hemolysis
[kernicterus = hypotonia + lethargy + seizures]
Conjugated hyperbilirubinemia
1- Intrahepatic cholestasis
- Hepatitis → alcoholic, A-D, EBV, CMV
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Post operative cholestasis e.g. ■ ®
 Ischemia
 Anesthetics
- TPN → intra, extra
- Cholestasis of pregnancy
 HELLP syndrome
 Intrahepatic cholestasis of pregnancy
 Acute fatty liver of pregnancy
- Infiltrative disorders
 Granulomatous → sarcoidosis, TB, Wegner's granulomatosis
 Malignancy
 Amyloidosis
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 - Infections → sepsis, bacterial, fungal or parasitic
- Vascular
 Budd-Chiari syndrome
 Ischemic hepatitis (shock liver)
- Stem cell transplant related
 Sinusoidal obstruction syndrome
 Graft versus host disease
 Chemotherapy induced hepatitis
- Drugs
 Anabolic steroids
 Oral contraceptives, estrogens
 Amoxicillin clavulanic acid
 Erythromycin
 Tricyclic antidepressants
 Terbinafene
2- Extrahepatic cholestasis
- Choledocholithiasis → common bile duct stones
- PSC
- AIDS cholangiopathy
- Malignancy
 HCC [tumor thrombus, compression, hemobilia]
 CCC
 Pancreatic cancer
 Ampullary tumors
- Pancreatitis → acute or chronic
- Mirizzi syndrome [gallstones compressing the common hepatic duct]
- Postsurgical strictures
- Choledocal cystic disorders
 Caroli's disease
 Choledochal cysts
- Vascular enlargement from
 Aneurysm
 Portal cavernoma
3- Congenital and familial
- Rotor syndrome
- Dubin-Johnson syndrome
- Progressive familial intrahepatic cholestasis
- Benign recurrent intrahepatic cholestasis

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Mixed conjugated and unconjugated
1- Hepatocellular disorders
- Viral hepatitis
- Alcoholic hepatitis
- Autoimmune hepatitis
- Wilson's disease
- Alpha -1 antitrypsin ↓
- Hemochromatosis
- Reye's syndrome
- NASH
- Celiac sprue
- Acute fatty liver of pregnancy and preeclampsia
2- Drugs
- Acetaminophen
- Salicylate and NSAIDs
- Clindamycin
- Colchicines
- Ketoconazole
- Amiodarone and Ca channel blockers
Complications
1- Kernicterus if bilirubin > 20 mg/dl seen in infants
2- Mechanical obstruction of the extrahepatic ducts can predispose to
- Cholangitis
- Secondary biliary cirrhosis
- Hepatic abscess
- Pancreatitis
3- Long term complications
- Hepatic osteodystrophy
- Malabsorption of fat and fat soluble vitamins
- Pruritus

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Treatment [depends on the cause e.g.]
1- Bile duct obstruction
- Aim → drain the bile to ↓ the risk of complications and to provide
symptom relief
- In case of choledocholithiasis
 Laparoscopic cholecystectomy with common bile duct
exploration using intraoperative or postoperative ERCP is
recommended
- In many cases of CBD stones
 ERCP with sphincterotomy and stone extraction is appropriate
- In patients unfit for surgery
 Externally inserted drains into the gallbladder or main hepatic
ducts is suggested to overcome malignant strictures or for
temporary relief of symptoms
2- Drug or toxin discontinuation
- Give N-acetyl cysteine for acetaminophen toxicity
3- Acute or chronic viral hepatitis
4- Autoimmune liver diseases
- Steroids , immune modulators or liver transplantation
Approach to diagnosis
History
1- Age
- > 65 → malignancy, gallstones, drug hepatotoxicity
- < 30 → acute viral or alcoholic hepatitis, AIH, biliary tract disease
2- Sex
- Female → gallstones, PBC, AIH, pregnancy related
- Male → pancreatic cancer, HCC, alcoholic or hemochromatosis
3- Onset
- Acute versus chronic [suggestive features of chronic disease]
 Spider angiomata, ascites, HSM
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  Fever, chills, right upper quadrant pain, leukocytosis and
hypotension → indicate ascending cholangitis (complication of
chronic case)
 ↓ albumin, ↑ PT and thrombocytopenia
4- Prodroma of viral hepatitis or risk exposure → acute viral hepatitis
5- Medication history
6- Alcohol abuse
7- Recent surgery
8- Pruritus → long standing biliary obstruction
9- Abdmonal pain
- Epigastric and radiating to back → suggest pancreatic disease
- Right upper quadrant → viral hepatitis
Examination
1- Chronic liver disease and cirrhosis
- E.g. Muscle wasting, palmar ertyhema, spider angiomata, ascites, caput
medusa
2- Liver size and consistency
- Shrunken nodular liver → cirrhosis
- Palpable mass → malignancy or abscess
- Enlarged liver > 15 cm → NAFLD, infiltrative disease or congestive
hepatopathy
3- Xanthomas → PBC
4- Kayser-Fleisher rings → wilson's disease
5- Hyperpigmentation → hemochromatosis
Laboratory studies
1- Essential initial tests → Bilirubin (total, direct), AST,ALT, ALP, PT, serum
albumin and total proteins
2- If results consistent with unconjugated hyperbilirubinemia → hemolysis
workup

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 - Reticulocytic count, CBC, LDH, peripheral smear, haptoglobin and
Coomb's test
- If no hemolysis → the most common cause of unconjugated is Gilbert's
disease
3- If results consistent with conjugated or indeterminate
- Transaminases > ALP → hepatocellular disorder
- Transaminases < 300 → alcoholic hepatitis, chronic liver disease or
DILI
- Transaminases > 1000 → acute viral hepatitis, ischemic hepatitis or
drug toxicity
- ALP ↑ (> 3 ULN) > transaminases → intrahepatic cholestasis or
extrahepatic obstruction [↑ GGT, 5'nucleotidase confirm hepatic origin
of ALP]
- High levels of bilirubin and ALP → CBD stone
- Disproportionate elevation of ALP compared with bilirubin → partial
biliary obstruction or early intrahepatic cholestasis (PBC, PSC)
4- ↓ albumin or prolonged PT → chronic liver disease
- Prolonged PT may be seen in obstructive jaundice  parenteral vitamin
K corrects coagulopathy in obstructive jaundice but not hepatocellular
disease
- High cholesterol → cholestasis
5- If initial evaluation not reveal etiology [drug, infection, alcohol, obstruction]
 specific studies
- Viral hepatitis markers
- ANA, AMA, SMA, immunoglobulins
- Iron saturation and ferritin
- Alpha-a antitrypsin level

135
Imaging
1- If tender hepatomegaly + ascites + abdominal pain (BCS) or initial
evaluation suggests shock liver
- Doppler U/S [to evaluate patency of the hepatic and portal veins and
hepatic artery]
2- If initial evaluation suggestive of malignancy
- U/S, Triphasic CT scan and alpha fetoprotein is considered
3- Patients with ↑ ALP  should be evaluated for causes of cholestatic jaundice
- U/S → the initial study
 Detect biliary obstruction as evidenced by ductal dilatation
 Also can identify gallstones, cirrhosis and other hepatic
parenchymal lesions
- CT
 1ST study for evaluation of hepatic parenchymal lesions
 Also ductal dilatation
- HIDA scan (hepatic iminodiacetic acid scan)
 Test of choice if acute cholecystitis with cystic duct obstruction
or biliary leakage is suspected
- MRI  malignancy, liver fat and iron
- MRCP → asses the biliary tract
- If ductal dilatation is present in U/S or CT or if the suspicion of
obstruction remains high despite normal studies  ERCP or PTC [note
that patients with prior cholecystectomy normally have a dilated CBD]

- ERCP
 Direct visualization of the biliary and pancreatic ducts
 Identify site of obstruction in > 90% of cases
 Therapeutic options [sphincterotomy, stone extraction, stent
placement, cytology and brushing]

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  Complications → pancreatitis, cholangitis, bleeding and
perforation (2-3%)
- PTC → Evaluate biliary obstruction [CI if PT> 16 sec. and PLT
<50,000) and ascites
- Endoscopic U/S
 Detect small CBD stones with ability to remove it
 Detect small (<3 cm) pancreatic tumors not seen by CT
- If imaging studies are inconclusive and a hepatocellular process is
suspected  liver biopsy

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Occult/obscure bleeding

Definition  see before

Method for occult blood examination  see before
Causes
1- The most important cause of occult bleeding is GIT tract cancer
2- Neither aspirin nor warfarin alone cause +ve occult blood test, so further
evaluation required
Obscure GI Bleeding Summary Causes
Causes within reach of upper
Causes beyond reach of upper endoscope
endoscope
Erosions within hiatal hernia (Cameron’s Angiodysplasia
erosions)
Esophagitis Small bowel tumor

Angiodysplasia Small bowel ulcers and erosions, including NSAIDS/other

drug-induced lesions
Gastritis Crohn’s disease

Gastric polyps Celiac sprue

GAVE Small bowel tics

Dieulofoys small bowel varices

Celiac sprue Lympagioma

Radiation enteritis

Blue rubber bleb nevus syndrome

Osler weber rendu

VWB,, gardners, aortoenteric fistula, amyloidosis,

Meckels, hemosuccus pancreaticus, hemobilia

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Approach to diagnosis & treatment  the same as small bowel bleeding

Obscure GIT bleeding

 If pt continues to bleed
1- Mesenteric angiography to localize bleeding site

o requires > 0.5 cc per minute of blood loss

o injection of autologous clot or small pieces of gelatin sponge (Gelfoam) to embolize
arteries supplying localized bleeding sites
o infusion of vasopressin 0.1 – 0.5 units/min into the arterial supply of the bleeding site
effective in controlling bleeding
2- Capsule endoscopy

3- Enteroscopy

4- Tagged RBC scan

o can detect bleeding at > 0.1cc per minute

o unreliable localization, high false positive rate

139