EPIDEMIOLOGY

• Prevalence 10%

• F>M (2:1)

• Incidence increases with age

“ Female, fat, fertile, fifty, fare”- kind of true.

AETIOLOGY

1. Cholesterol supersaturation.

• Cholesterol normally dissolved in lecithin-bile acid.

• If the concentration of cholesterol increases, no more can dissolve ie supersaturated.

• Supersaturation occur in:

* High oestrogen states= Obesity, pregnancy, Pill.

*Decreased bile acid pool = terminal ileum disease/resection.

Therefore, enterohepatic circulation disrupted.

2. Stasis.

• Fasting: no food stimulus for GB emptying.

• TPN: As above

• Truncal vagotomy: No neural stimulus to GB

3. Increased Bilirubin secretion in bile or deconjugation.

• Bilirubin is kept soluble in bile by conjugation with glucuronide.

• Pigment stones occur when:

1. Increased breakdown of RBC: Haemolytic anaemias, Spherocytosis, SCD.

2. Failure of conjugation: Hepatocyte insufficiency to form glucuronide or XS glucuronidase. Increased bacteria as cause or effect?

• Cholesterol stones (20%):

1. Solitary or multiple.

2. High cholesterol states, pregnancy, DM, Pill.

3. Strawberry Gall Bladder- is cholesterosis of GB with mucosa studded with sub-mucosa cholesterol.

• Bile pigment stones (5%):

1. Small, black, irregular, multiple and gritty.

2. Haemolytic anaemias.

• Mixed stones (75%)

1. Multiple.

2. Generations of stones

3. Due to precipitation of cholesterol.

GALL BLADDER:

• Biliary colic
• Acute cholecystitis
• Empyema
• Mucocele
• Chronic cholecystitis.

COMMON BILE DUCT:

• Obstructive jaundice.
• Cholangitis
• Pancreatitis.
  

SMALL INTESTINE:

• Gall stone ileus.

Biliary Colic

• Stone impacts in neck of GB
• Sustained GB contraction = increased pressure in GB = PAIN.
• Pain in RUQ  epigastrium and lower pole of scapula.
• Biliary colic has a slow periodicity.  30mins –2 hrs.
• Apyrexial.
• WCC & CRP normal.
• X-ray- 10% galls stones seen.
• USS- detects 98% of GS
• Management: Analgesia,Cholecystectomy

Acute cholecystitis

• A stone impacts at the GB outlet.
  
• Similar symptoms to colic but > 12hrs.
  

Pathology

• Impaction of stone in cystic duct.

• Sustained high pressure in GB, therefore decreased blood flow to mucosa.

• Mucosal damage by detergent action of bile.

• !st, chemical cholecystitis with inflammation and oedema of GB wall. 2^nd, bacterial infection --> 48 hrs.

Clinical Features

• Pain RUQ

• MURPHY’S SIGN: When the examining hand is placed in theRUQ and patient inhales = PAIN

• BOAS’S SIGN: Hyperaesthesia of skin on 9-11 ribs

Investigations

• WCC

• Bilirubin

• serum Amylase

Imaging: USS

Management:

• Initially conservative: Analgesia and Antibiotics.

• If symptoms do not resolve, operation. Why-> Gangrene at fundus -> peritonitis.

Empyema

• If no perforation occurs, GB remains inflamed.

• Contents become purulent. Bacteria and neutrophil exudates.

• Essentially an abscess with GB wall as casing
  
  

Mucocele

• Impacted stone with no bacterial overgrowth.

• Mucosa inflamed and cont to absorb water from bile and secrete mucous.

• People get cont. RUQ pain cholecystectomy.
  
  

Chronic Cholecystitis

• Essentially, chronic symptoms of acute attacks.

• GS on USS.

• GB thick fibrotic wall.

• 10-14 % of patients with GS have duct stones.

• Duct stones are responsible for:

1. Obstructive Jaundice:

• Jaundice, dark urine, pale stool, pririts.

• alk phos with min ALT 

•  bilirubin

• USS = dilated bile ducts.

• ERCP and cholecystectomy in future.

2. Acute Cholangitis:

• Organsims enter biliary tract via duodenum or blood via liver.

• Western world = ductal stones and bacteria eg E.coli

• Pacific rim = parasites: liver flukes and ascariasis.

• In not treated fatal.

Hernia is defined as an abnormal protrusion of a viscus or a part of viscus through as opening , artificial or natural with a sac covering it.

Common hernias :

• Inguinal hernia
• Incisional hernia
• Femoral hernia
• Umbilical hernia

Causes :

• coughing
• obesity
• straining
• Intra-abominal malignancy

Parts-

• covering
• sac - narrow in indirect hernia, wide in direct hernia( fundus,body , neck)
• content

Hernia without neck- direct hernia, incisional hernia

Classification :

• Reducible
• Obstructive
• Strangulated
• Irreducible
• Inflammed

Taxis
used in irreducible or partially reduced hernia
trial reduction by flexing and medially rotating the hip

Different types of hernia -

1. Gibbon's hernia- hernia with hydrocoele
2. Berger's hernia - hernia in Pouch of Douglas
3. Grynfelt/s hernia- Upper lumbar triangle hernia
4. Petit's hernia - Lower lumbar triangle hernia
5. Cloquet's hernia- hernia through pecteineal fascia
6. Narath's hernia - behind femoral artery
7. Hesselbach's hernia - lateral to femoral artery
8. Serofini's hernia - behind femoral vessels
9. Laugier's hernia - through lacunar ligament
10. Tealse's hernia - in front of femoral vessels
11. Richter's hernia - part of circumference of bowel wall is gangrenous
12. Littre's hernia - hernia with Meckels's Diverticulum
13. Sliding hernia - Posterior wall of sac is formed by colon or bladder
14. Maydl's hernia - 'w' hernia
15. Phantom hernia - Localised muscle buldge following muscular paralysis
16. Spigelian hernia - through spegelian fascia
17. Obturator hernia - through obturator foramen
18. Femoral hernia - hernia medial to femoral vein
19. Beclard's hernia - femoral hernia through saphenour opening

Use 5 fingers of hand to complete all test of hernia:

Thumb - for deep ring occlusion test
Index, middle and ring finger - Ziemanp's test
Little finger - for superficial ring invagination test

Rules for hernial examination:

Never forget to examing opposite site.
Never forget to do per rectal examination.
Never forget to examine urethra.
Never forget to check abdominal muscle tone.

Preparation of work area to be used

a) Close nearby windows
b) Pull curtains around bed
c) Restrict activities around bed, e.g. dusting or mopping floor.


Preparation of Patient

a) Explain procedure to patient
b) Assist patient into suitable position that is both comfortable for them and convenient for
the procedure.
c) Clear space around wound of any blankets, receptacles, etc.

Procedure

To achieve aseptic technique use either a no-touch technique (e.g. use forceps) or use a
gloved technique using the basic dressing pack. There is no need to use both.
a) Take trolley to bedside.
b) Loosen dressing.
c) Decontaminate hands with alcohol based hand-rub.
d) Peel open dressing packet and empty contents onto top shelf.
e) Open sterile field by holding outer corners of paper sheet / wrapper.
f) If necessary pour cleansing fluid into plastic tray and add any supplementary items, e.g.
forceps or dressing.
g) Pick up yellow bag by corner.
h) Place hands into the bag by using this as a glove, collect the dirty dressing from the
wound.
i) Invert the bag with the dressing inside.
j) Remove backing tape from adhesive strip on yellow bag and then stick the bag to the
trolley – if not appropriate, a clip may be used.
k) Inspect wound, take laboratory swab / specimen if necessary.
l) Decontaminate hands with alcohol based hand rub.
m) Put gloves on with minimum touch, if wound needs aseptic attention.
n) If needed, gently cleanse the wound using non woven gauze swabs.
o) Any non disposable instruments used should be placed in the pulp tray on lower shelf.
p) Apply the dressing as prescribed.
q) Dispose of all used items into the waste bag. Seal the bag carefully.
r) Make the patient comfortable.
s) Remove trolley from bedside / treatment area.
t) Dispose of waste bag into yellow bin bag for incineration. Used instruments into dry,
covered container for HSSU. Both kept in dirty utility room.
u) Wash / decontaminate hands.
v) If infected waste has contaminated the trolley surfaces, wash with detergent and hot
water. Dry well.
w) Report and record condition of patient’s wound.

Preparation of equipment

a) When the treatment room is cleaned in the morning, trolleys should be washed with
general purpose detergent and dried.
b) Before each dressing wash and dry hand or decontaminate with alcohol hand-rub.
c) Top shelf: - Left empty
Bottom shelf: - Basic dressing pack
- Suitable lotion
- As you place packs onto trolley first check that they are sterile
and undamaged

If required, add: - Supplementary packs
- Instruments
- Pulp tray to receive used instruments
- Special dressings
- Bandage or adhesive tapes
- Extra disposal bag

The aim of dressing any wound is to produce conditions in which healing can take place.
Choice of a suitable dressing material is an important part of infection prevention and the
healing process.

Non-surgical wounds, such as pressure sores, require hygienic rather than aseptic technique.
Similarly, there is little point in using a full aseptic technique to dress a clean surgical wound,
when the patient has just taken a bath or shower. Sterile materials are required, but the
dressing technique can be greatly simplified.

Traumatic wounds, pressure sores and varicose ulcers may be heavily colonised by bacteria,
although not necessarily showing signs of infection. The patient therefore may be an
infection risk to others. An occlusive dressing material such as hydrocolloid should be
considered both to promote healing and to prevent contamination of the patient’s immediate
environment.

Differential Diagnosis:

Stones:

History

• Continuous loin to groin pain
• Suggesting ureteric stone
• Dull and aching pain
• Suggesting stone in minor/major calyces
• Hematuria
• Vomiting
• Sweating
• UTI symptoms
• Risk factors
Poor fluid intake
• 
  
• Hyperparathyroidism
• Examination – Patient in agony

Benign Prostatic Hypertrophy:

History

Elderly men
• 
  
Symptoms of
• 
  
• Obstruction
• Poor, intermittent stream
• Hesitancy
• Dribbling
• Retention
• Irritative
Frequency
• 
  
• Urgency
• Nocturia
• Renal failure
• Drowsiness
• Headaches
• Disorientation
  

Examination

• 
  
• Uremia
• Pale and wasted
• Dry furry tongue
• Mentally confused
• Large bladder
• DRE
• BPH
• Lateral lobes enlarged
• Sulcus palpable
• CA
• Posterior part hard and craggy obliterating sulcus

Bladder Tumors:

History

• Painless gross hematuria
• Older patient
• With/without irritative symptoms (ulcerating CA)
• Risk factors
• Smokers
• Industrial chemicals
• Dye and rubber industry
• Radiation therapy

Examination

• Malignant tumor
• Felt on bi-manual exam
• Pale
• Cachexic
• Anemic
• Benign
• May be negative

Acute Nephritis (post strep. glomerular nephritis):

History

• Young child with history of
• Sore throat
• Ankle face swelling
• Recurrent infections
• Examination
• Edema
• Peri-orbital swelling
  

Renal Cell CA:

History

• Flank pain *
• Hematuria
• Weight loss
• 40-60 yr
• Male > female

Examination

• Palpable mass *
• HTN *
• Cachexia
• * Classical Triad

UTI (Cystitis):

History

• Females predominate
• Sequelae of
• Sex
• Urethral catheterization
• Symptoms of urgency
• Frequency and dysuria
• Fever and loin pain (ascending infection)

Examination

• Pyrexia
• Suprapubic tenderness
• Loin tenderness

Investigations:

• CBC
• Hb
• Reduced in CA
• Reduce in BPH due to uremia
• WBC
• Increased in UTI
• Platelets
• Thrombotic Thrombocytopenic Purpura (TTP)
• U&E
• Increased urea due to BPH
• Kidney function
• PT/PTT/INR & FDP
• Anticoagulant drugs
• LFT
• Metastases in Ca
• Increased ALP
• PSA
• Serum calcium, phosphate, & uric acid
• Urine
• Microscopy
• Pus cells and organisms in infection
• Casts in nephritis
• Culture
• To identify organism
• If no active bleed
• IVP
• Filling defects in bladder
• Kidney: shows stones
• Back pressure of kidneys in BPH
• Cystoscopy
• Bladder CA and biopsy
• Abdominal ultrasound
• Kidney mass/polycystic kidney disease
• Calculi in bladder
• If bleeding
• Catheterise
• Irrigate bladder
• Cystoscopy

Treatment:

• Fluid resuscitate if necessary
• Treat underlying condition
• Stones
• Pain relief
• 90% will pass
• Increase fluid intake (2L a day minimum)
• Change the precipitating diet (dairy/red meat/tea/red wine)

Surgery

• 
  
• Nephrolithotomy(PCNL)/pyelolithotomy
• Lithotripsy (ESWL)
• Note – Urethral stones are a surgical emergency: Urethrotomy
• UTI
• Antibiotic and then treat underlying cause e.g. stones, BPH
• Bladder CA
• Transurethral resection of the bladder (transurethral cystectomy)
• Radical cystectomy and chemotherapy
• BPH
• Medical
• Proscar (Finasteride)
• Inhibits 5 Alpha Reductase
• Alpha blockers
• Prazosin
• Relaxes prostatic smooth muscle

Surgical Indications

• Urinary retention
• Hydronephrosis
• UTI’s
• Severe symptoms

TURP (transurethral resection of prostate)

Complications of TURP
Failure to void
Bleeding
Clot retention
UTI
Incontinence
Open prostatectomy (rarely done)

Tags: turp, prostate, surgery

Bladder neoplasms: >90% arise from transitional epithelium (most are malignant); bladder carcinomas clinically features:

• Painless hematuria

• Frequency, urgency, dysuria (urinary symptoms)

• Later pyelonephritic complications

Majority of urothelial cancers are caused by exposure to environmental agents; therefore bladder tumours are usually multiple and often found in conjunction with urothelial tumours at other sites of lower urinary tract (e.g. renal pelvis, ureters or urethra).

Aetiology: frequently multifactorial…

• Chemicals: exposure to environmental agents excreted in high concentrations in the urine e.g. cigarette smoking (direct carcinogen, aberrant tryptophan metabolism and toxic metabolites), aniline dyes, rubber etc (many associated with certain industrial occupation)

• Premalignant conditions: e.g. bladder diverticular (3% complicated with tumour), schistosomiasis (esp. SCC)

Other possible factors include: diets high in fat or protein, cyclophosphamide exposure, genetic abnormalities and analgesic abuse.

Clinical course:

All (high grade more than low grade) have a tendency to recur; may be in different sites and tend to exhibit greater anaplasia

Prognosis related to histological type, growth pattern, grade, and stage; other factors e.g. p53, c-myc expression, HCG production, karyotype etc.

Death may be due to renal failure (obstruction and infection) and disseminated carcinoma (direct, lymphatic or haematogenous).

The salivary glands are the site of origin of a wide variety of neoplasms. The histopathology of these tumors is said to be the most complex and diverse of any organ in the body.

Salivary gland neoplasms are also relatively uncommon with an estimated annual incidence in the United States of 2.2 to 2.5 cases per 100,000 people; they constitute only about 2% of all head and neck neoplasms .

Nearly 80% of these tumors occur in the parotid glands, 15% in the submandibular glands and the remaining 5% in the sublingual and minor salivary glands.

Benign neoplasms make up about 80% of parotid tumors, 50% of submandibular tumors and less than 40% of sublingual and minor salivary gland tumors.

The pleomorphic adenoma or benign mixed tumor is the most common of all salivary gland neoplasms. It comprises about 70% of all parotid tumors, 50% of all submandibular tumors, 45% of minor salivary gland tumors but only 6% of sublingual tumors.

• The most common location of occurrence is the parotid (85%) followed by the minor salivary glands (10%), in which the palate, upper lip and buccal mucosa are most commonly affected.
  
• These tumors are most often diagnosed in the 4^th to 6^th decades of life and are uncommon in children although they are second only to hemangiomas in this population.
  
• They are seen more frequently in women with a female-to-male ratio of 3-4:1.

The typical clinical presentation of a pleomorphic adenoma is a slow-growing, painless and firm mass. In the parotid, 90% occur in the superficial lobe and most commonly are seen in the tail of the gland. Minor salivary gland pleomorphic adenomas most commonly occur on the lateral palate and are covered with normal appearing mucosa. In all locations, they are typically nontender to palpation and tend to be mobile when small but may become fixed with advanced growth.

These tumors are nearly always solitary although rare cases of synchronous or metachronous salivary neoplasms have been reported- either involving a second mixed tumor or a distinct lesion, most commonly Warthin’s tumor.

Facial nerve paralysis in association with pleomorphic adenomas almost never occurs, even with extremely large tumors.

The gross pathologic appearance of a pleomorphic adenoma is a smooth or lobulated, well-encapsulated tumor that is clearly demarcated from the surrounding normal salivary gland. They are typically solid tumors and may have areas of gelationous myxoid stroma. Cystic degeneration or tumor infarction and necrosis are rarely seen except in large, long-standing lesions. Microscopically, these tumors are composed of varying proportions of gland-like epithelium and mesenchymal stroma. The epithelial cells may display several different patterns of growth—small nests, solid sheets, ductal structures or anastamosing trabeculae. The stroma is just as variable and may be myxoid, chondroid, fibroid or osteoid. Also on microscopic examination, the incomplete encapsulation and transcapsular growth of tumor pseudopods characteristic of pleomorphic adenoma are demonstrated.

Treatment of pleomorphic adenomas is complete surgical excision with a surrounding margin of normal tissue, i.e., superficial parotidectomy with facial nerve preservation, submandibular gland excision or wide local excision for a minor salivary gland. Simple enucleation of these tumors is what is believed to have led to high local recurrence rates in the past and should be avoided. Rupture of the capsule and tumor spillage in the wound is also believed to increase the risk of recurrence, so meticulous dissection is paramount.

The second most common benign parotid neoplasm is Warthin’s tumor, also known as papillary cystadenoma lymphomatosum. It makes up 6-10% of cases of parotid tumors and has only rarely been described as occurring outside the parotid gland. It is primarily a disease of older white males, often being diagnosed in the 4^th to 7^th decades of life and occurring with a male-to-female ratio of approximately 5:1. Bilateral or multicentric Warthin’s tumors are seen in 10% of cases. Three percent are associated with other benign or malignant tumors.

Like the pleomorphic adenoma, Warthin’s tumors typically present as a slowly enlarging, painless mass. They tend to be firm or rubbery in texture and may be nodular. A minority of patients may report rapid enlargement of the tumor with associated pain or pressure.

Grossly, a Warthin’s tumor possesses a smooth lobulated surface and a thin but tough capsule. The diagnosis is often obvious just by the appearance of the cut surface of the tumor. Multiple cysts of varying diameter and containing variably viscous fluid are seen. The lining of the cysts appears shaggy and irregular. The lymphoid component makes up the solid areas of the tumor and lymphoid follicles can occasionally be seen. The pathognomonic microscopic features are epithelial cells forming papillary projections into cystic spaces in a background of a lymphoid stroma. The epithelium is a double cell layer with tall columnar cells lining the cystic spaces and cuboidal cells along the basement membrane. The nuclei of the columnar cells is oriented toward the cystic space while the cuboidal cell nuclei is oriented toward the basement membrane.

Treatment of Warthin’s tumors is surgical resection. Enucleation of the tumor may be adequate therapy but superficial parotidectomy with facial nerve preservation is the standard management.

Oncocytomas are rare tumors that constitute only 2.3% of benign epithelial salivary gland neoplasms.

• They are most often encountered after the sixth decade of life with a nearly equal male-to-female ratio of occurrence.
  
• The majority of these tumors affect the parotid gland (78%), few affect the submandibular gland (9%), none are reported in the sublingual gland and minor salivary gland involvement is most often in the palate, buccal mucosa or tongue.

The clinical presentation of oncocytomas is essentially identical to other benign salivary tumors—a slowly growing, nontender mass, typically in the superficial lobe of the parotid. They are firm, may be multilobulated and mobile on exam. Oncocytomas, along with Warthin’s tumors, have been noted to demonstrate increased uptake of pertechnetate anion and therefore can be distinguished from some other neoplasms by using technetium-99m pertechnetate scintigraphy.

Gross pathology findings include a homogenous tumor with a smooth surface that may be divided into lobules by fibrous tissue septae. Microscopically, there are sheets, nests or cords of uniform oncocytes. These cells are large with distinct borders and filled with an acidophilic granular cytoplasm. The granularity of the cytoplasm is due to the presence of large numbers of mitochondria that may constitute up to 60% of the cell volume.

Special staining procedures such as the phosphotungstic acid hematoxylin stain, Bensley’s aniline-acid fuchsin or Luxol-fast-blue reaction take advantage of this unique characteristic and can help to make the diagnosis of oncocytoma, as can electron microscopy.

Standard treatment of oncocytomas is surgical excision with a margin of normal tissue. There is an exceedingly low rate of recurrence of these tumors if removal is complete. Enucleation or curettage is not appropriate.

The term “monomorphic adenoma” refers to a group of rare salivary tumors that includes the basal cell, canalicular, sebaceous, glycogen-rich and clear cell adenoma. Of these, the basal cell adenoma is the most common. It constitutes 1.8% of benign epithelial salivary gland tumors and typically occurs in the 6^th decade of life. There are conflicting reports of gender predilection for this tumor but it does seem to occur more frequently among Caucasians than African Americans. The majority of basal cell adenomas occur in the parotid gland where they present as a slowly enlarging firm mass. They are well-encapsulated, smooth tumors on gross inspection and are divided into four subtypes based on their microscopic appearance—solid, trabecular, tubular and membranous.

The presentation of canalicular adenoma peaks in the 7^th decade of life and, like the basal cell adenoma, is more common in whites than blacks. There is a female predominance with a female-to-male ratio of occurrence of 1.8-1. This tumor most commonly involves the minor salivary glands of the upper lip (74%) or buccal mucosal (12%). Clinically it presents as a nonpainful submucosal nodule. On gross pathologic examination, canalicular adenomas may or may not possess a capsule and it is not unusual for there to be multifocal growth. Microscopically there are cords of single-layer columnar or cuboidal cells forming duct-like structures in a background of fibrous stroma.

The majority of monomorphic adenomas display nonaggressive behavior and are adequately treated with surgical excision.

Mucoepidermoid carcinoma is the most common salivary gland malignancy and makes up between 5 and 9% of all salivary gland neoplasms. It develops most commonly in the major salivary glands, most often the parotid (45-70%). The second most common site of occurrence is the palate (18%). This tumor displays a uniform age distribution between the ages of 20 and 70 years, with a slight peak in occurrence in the 5^th decade. Although it is rare before age 20, it is the most common salivary gland malignancy in the pediatric and adolescent populations. Mucoepidermoid carcinoma occurs more frequently in women than in men and in Caucasians than in African Americans.

The clinical presentation of a salivary gland malignancy can be very similar to that of a benign lesion. Often the only complaint is the presence of an enlarging but asymptomatic mass. Occasionally patients will report a rapid enlargement of a previously stable mass. Symptoms such as pain, fixation to the surrounding tissues or skin or facial paralysis are uncommon and should increase suspicion for a high-grade tumor. A mucoepidermoid carcinoma occurring in an intraoral minor salivary gland will often be mistaken for a benign or inflammatory process. It is not unusual for them to appear as a bluish or red-purple, soft and smooth growth. Others may present with a papillomatous appearance or as a hard submucosal mass, identical to a torus.

On gross inspection, some mucoepidermoid carcinomas appear well-circumscribed and may be partially encapsulated. Others are poorly defined and infiltrative. The cut surface of the tumor may contain solid areas, cystic areas or both. The cystic spaces contain viscous or mucoid material.

Microscopically, these tumors are characterized by the presence of two populations of cells—the mucus cells and the epidermoid cells, the proportion of which helps to define the grade of the tumor. Low-grade mucoepidermoid carcinoma is characterized by prominent cystic structures and mature cellular elements. This tumor contains proportionally more mucus cells, which may form gland-like structures, and fewer epidermoid cells. Intermediate-grade tumors display fewer and smaller cysts and occasional solid islands of epidermoid tumor cells. Although mucus cells are still present, there is an increasing proportion of epidermoid cells and occasional keratin pearl formation. The high-grade carcinomas are hypercellular, solid tumors with noticeable cellular atypia and frequent mitotic figures. These tumors will often be mistaken for a squamous cell carcinoma and the differentiation between the two can be quite difficult. Positive immunohistochemical staining for mucin indicates a high-grade mucoepidermoid carcinoma rather than a squamous cell carcinoma.

Appropriate therapy for mucoepidermoid carcinoma depends primarily upon the stage of disease, but is also influenced by tumor grade and location. Stage I and II disease can often be treated by surgical excision alone—parotidectomy with facial nerve preservation, submandibular gland excision or wide local excision of an involved minor salivary gland. Stage III and IV disease often require more radical excision and may warrant additional intervention such as a neck dissection or postoperative radiation therapy.

• Adenoid cystic carcinoma is the second most common salivary gland malignancy overall, but is the most common in the submandibular, sublingual and minor salivary glands.
  
• It occurs equally in men and women, peaks in the 5th decade of life and is more common in Caucasians.

Clinical presentation is often an asymptomatic mass, however, this tumor is more likely than others to present with pain or paresthesias. Facial paralysis remains rare, but again, may be seen more frequently with adenoid cystic than with other tumors. Minor salivary gland involvement is characterized by a submucosal mass with or without pain and ulceration.

Gross appearance is typically a well defined but not encapsulated mass that can be seen infiltrating surrounding normal tissue. Despite their name, these are solid tumors that rarely display obvious cystic spaces on the cut surface.

Microscopic appearance is described as cribriform, tubular or solid. The cribriform pattern is the most common and most easily recognizable. It is often referred to as the “swiss cheese” pattern. Tumor cells are arranged in nests around cylindrical spaces that may contain a mucinous or hyalinized material. Cells that are arranged in layers and form ductal structures characterize the tubular pattern. The solid pattern contains sheets of tumor cells with no intervening spaces.

Current treatment recommendations for adenoid cystic carcinoma include complete surgical resection and postoperative radiation therapy. Because of the propensity for this tumor to demonstrate perineural invasion, sacrifice of the facial nerve may be necessary for tumor eradication. Elective neck dissection is usually not indicated because this tumor rarely involves the cervical lymph nodes. Even with seemingly adequate treatment, local recurrence of adenoid cystic carcinoma is unfortunately not uncommon.

Tumor recurrence rates vary in the literature but reportedly can be as high as 42%. Another problem with this tumor is its propensity for distant metastasis, the most common site being the lung. Both local recurrence and distant metastasis can develop many years after initial treatment and multiple recurrences in the same patient have been reported. Although the prognosis for complete cure is poor, the course of disease is often indolent and patients with adenoid cystic carcinoma may survive for many years before eventually succumbing to the disease.

1. Positive strand RNA viruses—these include the:

   1. Picorna

   2. Toga

   3. Flavi

   4. Calici

   5. Coronaviruses

--their genome is processed to produce a long peptide that is then cleaved to produce viral subunits.

--their genomes look like mRNA

2. Negative Strand RNA viruses—their RNA is the opposite polarity of the mRNA and serves as a template.

Segmented –RNA viruses—have more than one piece of RNA in their genome.

• orthomyxovirus
• bunyavirus
• arenavruses
  

Non-segmented –RNA viruses—contain only one piece of RNA in their genome.

• Paramyxovirus
  Rhabdovirus
  
• Filoviruses

--these virions must carry the RNA-dependent-RNA polymerase.

--there are varying numbers of segments in the RNA—the segments code for different proteins and all segments must be present for an viable virion.

Ambisense genome—these negative strand RNA viruses have genomes that can be negative strand and another part is positive strand. They have more complex forms of replication/transcription. They are all single strands of RNA.

1. Arena virus

2. Bunyaviruses

Double stranded RNA virus—Reovirus and Rotavirus—genome serves as a template for mRNA transcription. Virions carry the RNA dependent RNA polymerase in the core. They have two copies of the + DNA but it is not paired—not really double stranded.

Retroviruses—the genome is positive single-stranded but it is not translated. The RNA is reversed to DNA via reverse transcriptase that is in the core of the virion.

Single cycle growth curve for a virus—a single cell is infected. Generally, the infected cell is infected with a MOI of 1 (1 particle per cell). Once the virus binds to the host cell it is internalized to the cytoplasm or to the nucleus. They undergo transcription and translation—then they assemble and the resulting progeny are released.

As MOI goes up, the previously infected cell is more immune to prior infections.

The first part of the cycle is the macro molecule synthesis. The early phase is characterized by the synthesis of molecules.—the late phase ends with the assembly of the virus particles.

Some viruses can produce up to 100,000 viruses per infected cell. Slower viruses like the retroviruses only produce about 1000 per cell.

Steps if viral cycle:

1. recognition and attachment to the host cell surface

2. penetration and uncoating

3. macromolecular synthesis

   1. transcription

   2. translation and modification of proteins

   3. replication

4. assembly

5. budding and release

Schematically—how does this happen?

At the stage of recognition/binding—viral attachment proteins bind to the receptors for the viral attachment proteins. This allows the virus to bind to the host cell. Those steps can be eliminated by antibodies that bind to the receptors or the viral proteins.

Once attached to the cell the virus must be internalized by one of three ways:

1. receptor-mediated endocytosis

2. Direct penetration

3. Fusion with the plasma membrane—for enveloped viruses only that have their own lipid bi layer.

--once inside the cell, the nucleocapsid undergoes uncoating. This step can be inhibited by drugs like amantadine. Once the viral genome is uncoated, it undergoes transcription.

If transcription occurs, we can stop it with antisense RNA. Interferon can also stop this process. Once the transcription occurs, mRNA is translated to produce proteins of viruses. This step can be blocked by interferon as well.

Assembly of the capsid without the viral genome in it occurs.

Then, replication—of the genome occurs. You have lots of both polarities of the RNA. Once the RNA is incorporated into the capsid, the virion is complete. They can then leave by budding or by lysing the cell.

Penetration results in the internalization of the virus or its nucleic acid.

1) Viruses penetrate cells through direct penetration such as the parvoviruses.
2) Fusion can also occur at the plasma membrane.

The retroviruses and the paramyxoviruses fuse with the membrane and are resopnseible for sycnctyium formation which is doue to the fusion of many adjacenet infected cells to generaget a giant cell containing many nuclei.

3) Receptor mediated endocytosis—this occurrs with the flu virus, rhabdovirus, and non-envoeloped viruses. Glycoproteins are used in this process and they can not get in unless the pH is low. This is facilitated by the fusion of the lysosome with the endosome—the pH drop allows for the release of the virus from the vesicle.

Segmented Negative strand RNA viruses

1. the negative strand enters the cell—the first event to occur is the transcription to produce the plus strand

2. the plus strand is then used to replicate the negative strand genome and

3. plus strands are also used to make proteins through translation—and viral proteins.

--this process occurs for all RNA segments in the genomes

Non-segmented Negative strand RNA viruses

1. the negative strand is transcribed to make a positive strand

2. the positive strands are used to make copies of the negative strand

3. the positive strands are used to make viral proteins that are subsequently cleaved to make the subunits of the virus capsid.

--for both of the above, the RNA-dependent RNA polymerase is used to make the positive strand RNA

Ambisense RNA Viruses

1. they have a genome that is one molecule of RNA that is both + and – in polarity

2. RNA-dependent RNA polymerase makes positive strands from the negative side that is used for translation

3. The same enzyme makes a positive copy of the negative side of the original.

4. From the positive copy made above, negative stands are used to make positive RNA copies for the genome.

Positive Stranded RNA viruses

1. the RNA can be directly translated

2. a copy of negative RNA is transcribed

3. From the negative copy, + copies of the genome are made

In other cases

1. the + strand is directly translated

2. a negative strand is made

3. from there copies of the genome are made as well as more positive transcripts that are used for translation.

Double stranded viruses

1. a positive strand is transcribed form the negative side

2. this is used for replication and for translation.

Retrovirusese—have two copies of the Same RNA

they are transcribed to produce DNA that is double stranded
this DNA is then transcribed to produce RNA again

Viral mRNA is translated into protein by host cell translation machinery.

Polyproteins are processed by viral as well as cellular proteases.

To enhance tran slation of their genomes, viruses employ several mechanisms- they have the internal ribosome entry sites (IRES) they cleave the CAP binding protein—at the 5’ RNA.

This host cell binds those caps on cellular mRNAs. By cleaving this protein, the ribosomes won’t pick up the cellular mRNA as much as it usually does. This makes it easier for the viral RNA to compete. they cleave the cellular mRNA’s

Viral proteins undergo a variety of post-translational modifications including polyprotein processing, phosphorylation and acylation.

Assembly and budding—non-enveloped viruses are generally assembled as empty capsids and the genome is then packaged. For enveloped viruses the matrix protein promotes the interaction of the viral nuclecapsid with the viral glycoprotein modified membrane for the assembly. Non-enveloped viruses are usually released by lysis of the host cell. Envoloped viruses are usually released by budding.

General strategy—the virus must enter the cell. Once inside it must transcribe its genome, replicate its genome, make viral proteins, assemble progeny viruses. Then it must get out of the cell.

For DNA viruses, transcription occurs in the nucleus of the cell. Transcription factors are important for the early phase of transcription and can come from the host cell, the virus or both.
Temporal regulation—timing of DNA transciption. Most have their transcription broken up into early genes and late genes. Early genes get transcribed immediately after the viral DNA gets into the nucleus. These genes influence the viral-cell interactions.

Viruses use alternative splicing patterns to increase the diversity of their gene products from a small amount of DNA. Some process RNA and some temporally regulate their transcription.

Latency—in the world of molecular virologists had to do with the activity of the virus within in the cell—incorporation of the viral genome into the host in the case of retroviruses. In clinical terms it is the absence of clinical symptoms.

Parvovirus—

smallest DNA virus that requires growing cells (B19) or helper virus. They carry no baggage with them—they have barely enough to enter and execute a viral cycle. The reason they need growing cells—they are replicating DNA actively—the virus needs the machinery used for DNA replication. They don’t grow well inside of static cells but do well in the bone marrow and would not grow well in the heart or CNS.

B19—one of the viruses that grows in the bone marrow and causes anemia.

It has single stranded chromosome with inverted repeats at the end of the linear molecule that fold back and serve as primers for DNA replication. During repplication, you get both positive and negative strands.

The positive and negative strands both get incorporated into progeny phage. IT is a lytic bacteria and destroys the host cell at the end of the cycle.

Papovavirus—small icosahedral viruses. They have double stranded DNA about 8 kb.

• Non-covalent interactions hold the capsid together. There is temporal regulation of transcription. There are early, late and non-coding DNA.
• The non-coding regions may be regulatory regions, but don’t code for protein.
• Early genes are the genes needed first and late refers to genes transcribed later.
• The early genes code for T antigen—(transforming proteins) that have the capabitity to interact with the cell to change its growth—usually they promote mitosis.
• Cells infected with this kind of virus are neoplastic-like.
• MRNA initiation—origin or replication (bi-directional)—forms of non-coding regions.
• Late genes—VP—structural proteins—assebly occurs in the nucleus.
• SP40 virus—famous history because of its use in research of oncogenic properties of viruses. It infects monkeys.

Adenoviruses—

• icosadeltahedral virus with fibers. It causes gastrointestinal infections.
  
• It has a double stranded DNA chromosome that is linear with a 5’ terminal protein. It transcribes from both strands.
  
• Early genes are transcribed from four different promoters. -transactivator genes as E1A and E1B—proteins that are important for cell-virus interactions.
  
• These genes promote transformation. This makes them neoplastic like.
• There is a viral coded DNA polymerase. It also has late genes that uses one promoter. Rthis virus has the capability of having a lytic cycle or latent cycles—the virus can just hang out in the nucleus. The oncogenic cycle exists in which the cell becomes neoplastic.
• Splicing mechanisms are used to make a more diverse set of proteins from the genome.

Herpes viruses—large enveloped icosadeltahedral virions. This is a complex virus.

• They are large and enveloped! They have a linear double stranded DNA chromosome. 100 million base pairs. It has unique regions that can be bracketed by direct repeat regions (seen mainly in epstien barr) while the inverted repeats are more common in the HSV, VZV, and CMV—these inverted repeats allow them to recombine to make unique strains.
• Immediate early genes give rise to DNA binding factors—they sit on the genome and regulate the genome expression of the virus.
• Early genes—DNA polymerase. These viruses contain a lot of their own enzymes.
• Herpes can regulate its own transcription pattern and can drive itself into latency and this occurs in neurons mostly. In this stage, there is no DNA replication. This is a molecular latency.
• Late genes encode the structural proteins.
• Latency can be broken and we are not sure exactly how, but there are physiological states that can precipitate this action.
• HSV 6 and EB don’t make unique strains—lack inverted repeats.

Pox viruses—large complex viruses. They have linear double stranded DNA genomes. They are so large that they can be seen with light microscopy.

• All replication events occur in the cytoplasm. This is the only virus that does it here.
• They encode all the proteins for mRNA and DNA synthesis. DNA replicates in the cytoplasmic inclusions.
• This virus is usually lytic.

Hepadnavirus—hepatitis B virus. The other forms of hepatitis are RNA viruses.

• This is an enveloped virus that is unique in that it uses a reverse transcriptase. IT has a circular double stranded DNA.
  
• The genome is partially double stranded.
  
• It encodes a reverse transcriptase—DNA is replicated using RNA intermediate.
• There are overlapping mRNAs in the genome. 3500base mRNA is the template for the genome.
• RNA-dependent DNA polymerase (RT) that uses a large mRNA— RNAase H is used to get rid of the leftover RNA
• Integrated genome—found in hepatocellular CA—this could be the connection b/w the infection of HepB and cancer.

Water-soluble vitamins

Thiamine (B₁) Anorexia, weakness, peripheral neuropathy, cardiac failure, cerebellar signs, Wernicke’s encephalopathy; collectively, termed beriberi

Riboflavin (B₂) Angular stomatitis, cheilosis, geographic tongue, skin desquamation, seborrheic dermatitis, anemia

Niacin Dermatitis, dementia, diarrhea, angular stomatitis, painful tongue, headache; collectively, termed pellagra

Pyridoxine (B₆) Seborrhea-like facies, cheilosis, glossitis, anemia, peripheral neuritis

Folic acid Anemia, sore tongue, mouth ulcers, nausea, diarrhea, depression, fatigue

Cobalamin (B₁₂) Insidious weakness, fatigue, sore tongue, paresthesia, lower extremity numbness, anorexia, diarrhea, hair loss, depression, dementia

Pantothenic acid Fatigue, paresthesia, weakness, “burning feet”

Biotin Alopecia, scaly dermatitis

Ascorbic acid (C) Weakness, irritability, gingivitis, joint and muscle pain, loose teeth, easy bleeding; collectively, termed scurvy

Fat-soluble vitamins

A Poor dark adaptation, xerophthalmia, dry skin, increased infections

D Tetany, muscle weakness, bone growth disorders (rickets), vertebral fractures, osteopenia (osteomalacia, osteoporosis)

E Areflexia, gait disturbance, paresis of upward gaze, other neurologic signs,

hemolytic anemia

K Bleeding, easy bruisability

• Definition- Essential organic substances needed in small amounts in the diet for normal function, growth and maintenance of the body

• Yield no energy to the body, they often participate in energy-yielding reactions

• A, D, E, K are fat soluble

• B, C are water soluble

• B, K function as parts of coenzymes (compounds that help enzymes function)

• Can’t be synthesized in the human body

• To be classified as a vitamin, a compound must meet criteria

  • Body is unable to synthesize enough of the compound to maintain health

  • Absence of the compound from the diet for a defined period of time produces deficiency symptoms

• Few vitamins have also proved useful in treating several nondeficiency diseases

• These medical applications require administration of mega doses (well above typical human needs for the vitamins

• Mega doses of a form of niacin can be used as part of blood cholesterol-lowering treatment for certain individuals

• Other examples of medical use include forms of vitamin D in the treatment of psoriasis

STORAGE OF VITAMINS IN THE BODY

• Fat-soluble vitamins are not readily excreted from the body

• Excess amounts of the water-soluble vitamins are generally lost from the body quite rapidly, partly because the water in cells dissolves these vitamins and excretes them out of the body via the kidneys

• Water-soluble vitamin B-6 and vitamin B-12 are exceptions

• An occasional lapse in the intake of even water-soluble vitamins generally causes no harm

• Symptoms of a vitamin deficiency occur only when that vitamin is lacking in the diet and body stores are essentially exhausted

• Average person must consume no thiamin for 10 days or no vitamin C for 20-40 days before developing the first symptoms of deficiency of these vitamins

VITAMIN TOXICITY

• Fat-soluble vitamins can easily accumulate in the body and cause toxic effects

• Toxicities of the fat-soluble vitamin A is the most frequently observed

• ‘one-a-day’ type of multivitamin and mineral supplement usually contains less than 2 times the Daily Values of the components regular use of these products is unlikely to cause toxic effects in men

• but highly potent sources of vitamin A can cause problems

PRESERVATION OF VITAMINS IN FOODS

• substantial amounts of vitamins can be lost from the time a fruit or vegetable is picked until it is eaten

• water-soluble vitamins can be destroyed with improper storage and excessive cooking

• heat, light, exposure to the air, cooking in water, and alkalinity are all factors that can destroy vitamins

• the sooner a food is eaten after harvest, the less chance of nutrient loss

• if the food is not eaten within a few days, freezing is the best preservation method to retain nutrients

• frozen vegetables and fruits are often as nutrient-rich as freshly picked ones

• fruits and vegetables are often frozen immediately after harvesting

ABSORPTION OF FAT-SOLUBLE VITAMINS

• Vitamins A, D, E, and k are absorbed along with dietary fat

• These vitamins then travel with dietary fats through the bloodstream to reach body cells

• Special carriers in the bloodstream help distribute some of these vitamins

• Far-soluble vitamins are stored mostly in the liver and fatty tissues

• When fat absorption is efficient, about 40% to 90% of the fat-soluble vitamins are absorbed

• People with cystic fibrosis, a disease that often hampers far absorption, may develop deficiencies of fat-soluble vitamins

• Some medications also interfere with fat absorption

• Unabsorbed fat carries these vitamins to the large intestine, where they are excreted in the feces

• Vitamins supplements are part of the treatment for preventing a vitamin deficiency associated with fat malabsorption

• The amount of vitamin A you consumer is very important as both deficiency and toxicity of this vitamin can cause severe problems

• There is a very narrow range of optimal intakes between these two states

• Vitamin A is found in foods in a variety of forms

• Retinoid or preformed vitamin A, are only found in foods of animal origin, such as fish and organ meats

• Plants contain pigments called carotenoids, which can be turned into vitamin A in the body as needed

• They can be termed provitamin A

• Beta-carotene, the orange-yellow pigment in carrots, if the most potent form of provitamin A

FUNCTIONS OF VITAMIN A AND CAROTENOIDS

Vision:

• Vitamin A performs important functions in light-dark vision, and to a lesser extent, color vision

Cardiovascular Disease Prevention

• Carotenoids may play a role in preventing cardiovascular disease in persons at high risk, possibly linked to carotenoids’ antioxidant capability

Caner prevention

• Coupled with its ability to aid immune system activity, vitamin A may be a valuable tool in the fight against cancer

• Carotenoids by themselves also may help prevent cancer, acting again as antioxidants

• Cancer of the prostate gland is one of the most common cancers among North American men

• Dietary carotenoid lycopene- red pigment found in tomatoes, watermelon, and other fruits

• The proposed biological role of lycopene again may be that of an antioxidant

VITAMIN A SOURCES AND NEEDS

• Vitamin A is found in liver, fish , fish oils, fortified milk and yogurt and eggs

• Provitamin A carotenoids mentioned before are mainly found in dark green and yellow-orange vegetables and some fruits

• Carrots, spinach, and other greens, winter squash, sweet potatoes, broccoli, mangoes, cantaloupe, peaches and apricots are examples of such sources

• Not just a vitamin; it is in face primarily considered a hormone.

• Skin cells can convert a cholesterol-like substance to the prohormone vitamin D, using sunlight

• Overall, sun exposure provides about 90% of our vitamin D needs

• Liver and kidney cells then convert the prohormone to its active hormone form

• The amount of sun exposure needed by individuals to produce vitamin D depends on their skin color, age, time of day, season, and location

• Experts recommend that people should expose their hands, face, and arms at least two to three times a week for 25% of the time it takes to turn ones skin pink (5-10 min) to make enough vitamin D

• Persons with dark skin would need additional exposure, about 3-5 times the amount just recommended

FUNCTIONS OF VITAMIN D

• Main function is to help regulate calcium and bone metabolism

• In concert with other hormones, especially parathyroid hormone, the vitamin D hormone closely regulates blood calcium to supply appropriate amounts of it to all cells

• The most obvious result of the vitamin D hormone action is increased calcium and phosphorous deposition in bones

• Without adequate calcium and phosphorus deposition during synthesis, bones weaken and bow under pressure (child with these symptoms-rickets)

• Osteomalacia (soft bones) is results from inefficient calcium absorption in the intestine or poor conservation of calcium by the kidneys

• This leads to fractures in the hip and other bones

VITAMIN D SOURCES AND NEEDS

• Few foods contain appreciable amounts of vitamin D

• Rich sources are fatty fish, fortified milk and yogurt, and some ready-to-eat breakfast cereals

UPPER LEVEL FOR VITAMIN D

• The upper level for vitamin D is 50 micrograms per day

• It’s based on the risk of overabsorption of calcium and eventual calcium deposits in the kidneys and other organs

• Fat-soluble antioxidant

• Resides mostly in cell membranes

• An antioxidant can form a barrier between a target molecule (an unsaturated fatty acid in a cell membrane) and a compound seeking its electrons

• The antioxidant donates electrons or hydrogens to the electron-seeking compound

• This protects other molecules or parts of a cell from having electrons stolen

• If vitamin E is not available to do its job, electron-seeking compound-known as a free radial- can pull electrons from cell membranes, DNA, and other electron-dense cell components

• This either alters the cell’s DNA, which may increase the risk for cancer, or injures cell membranes, possibly causing the cell to die

• This free-radical production is a normal result of cell metabolism and immune system function

• For example, white blood cells generate free radicals as part of their action to stop infection

• The body needs antioxidants like vitamin E to carefully regulate this exposure to avoid related undesirable effects

• Experts do not know whether megadose vitamin E supplements taken by otherwise healthy people confer any additional protection against cardiovascular disease and cancer than that achieved by improving diet (especially fruit, vegetable, and whole-grain bread and cereal intake)

• Deficiency of vitamin E causes cell membranes to break down

• When oxidative damage causes the cell membranes of red blood ells to break, it is called hemolysis

VITAMIN E SOURCES AND NEEDS

• Major sources of vitamin E include plant oils, ready-to-eat breakfast cereals, some fruits and vegetables (asparagus, tomatoes, and green leafy vegetables) eggs, whole grains, nuts, and seeds

• Plant oils are made up of mainly unsaturated fatty acids, and the vitamin E in plant oils protects these unsaturated fats from oxidation

• animal fats and fish oils have practically no vitamin E

• cell damage by free radicals occurs over an extended period of time

• beneficial effects of vitamin E and other antioxidants in counteracting this damage is most apparent when viewed over the long term

FUNCTIONS OF VITAMIN K

• vital for blood clotting

• k stands for koagulation

• activates proteins present in bone muscle, and kidneys

• poor vitamin K intake has been linked to an increase in hip fractures in women

• in adults, deficiencies of vitamin K have occurred when a person takes antibiotics for a long period

VITAMIN K SOURCES AND NEEDS

• Major food sources of vitamin K are liver, green leafy vegetables (kale, turnip greens, dark green lettuce, and spinach) broccoli, peas, and green beans

• Vitamin K is abundant in a balanced diet, and a deficiency in uncommon

• Most water-soluble vitamins are more readily excreted from the body than are fat-soluble vitamins

• Since any excess generally ends up in the urine or stool and very little is stored, consuming good sources of the water-soluble vitamins regularly is important

• Because they dissolve in water, large amounts of these vitamins can be lost during food processing and preparation

• Light cooking methods, such as stir-frying, steaming and microwaving, best preserve vitamin content

• B Vitamins are thiamin, riboflavin, niacin, pantothenic acid biotin, vitamin B-6, folate, and vitamin B-12

• B vitamins function as coenzymes, small molecules that interact with enzymes to enable enzymes to function

• In essence, the coenzymes contribute to enzyme activity

• As coenzymes, B vitamins play many key roles in metabolism

• The metabolic pathways used by carbohydrates, fats, and amino acids all require input from B vitamins

• After being ingested, the B vitamins are first broken down from their coenzyme forms into free vitamins in the stomach and small intestine

• The vitamins are then absorbed, primarily in the small intestine

• Once inside cells, the coenzyme forms are resynthesized

• Although some vitamins are sold in the coenzyme forms in health-food stores, there is no need to consume the coenzyme forms themselves

• These are broken down during digestion and we make them when needed

• Thiamin is used to help release energy from carbohydrates

• Major sources of thiamin include pork, products, whole grains, ready-to-eat breakfast cereals, enriched grains, green beans, milk, orange, juice, organ meats, peanuts, and dried beans, and seeds

• The coenzyme forms of riboflavin participate in many energy-yielding metabolic pathways

• When cells form cellular energy using oxygen-requiring pathways, such as when fatty acids are broken down and burned for energy, the coenzymes of riboflavin are used

• Major sources are milk, milk products, enriched grains, ready-to-eat breakfast cereals, meat, eggs

• Coenzymes forms of niacin function in many cellular metabolic pathways

• When cell energy is being utilized, a niacin coenzyme is used

• Synthetic pathways in the cell-those that make new compounds-also often use a niacin coenzyme (this is especially true for fatty acid synthesis)

• Most every cellular metabolic pathway uses a niacin coenzyme, a deficiency causes widespread changes in the body

• The group of niacin deficiency symptoms is known as pellagra, which means rough or painful skin

NIACIN SOURCES AND NEEDS

• Poultry, ready-to-eat cereals, beef, wheat bran, tuna and other fish, asparagus, and peanuts

• Coffee and tea also contribute some niacin to the diet

• Very heat stable; little is lost in cooking

• We can synthesize niacin from the amino acid tryptophan

• We synthesize 50% of the niacin we need

• Adult RDA of niacin is 14-16 milligrams per day

UPPER LEVEL FOR NIACIN

• 35 milligrams per day

• effects include headache, itching, and increased blood flow to the skin, causing a general blood vessel dilation or flushing in various parts of the body

• long run: GI tract and liver damage is possible, so any use of megadoses, including large doses recommended for treatment for cardiovascular disease, requires close physician scrutiny