Acute intussusception

It is telescoping or invagination of one portion of bowel into the adjacent segment. (proximal into distal)

Aetiology

• It is common in weaning period of child, between 3-9 mths.

• In children- associated with Meckls diverticulum, polyp, HSP, etc.

• In adolescents and adults- submucus lipoma, leiomyoma, polyps in jejunum (Peutz-Jeghar syndrome), other polyps and carcinoma with papillary projections.

Pathology

• Apex- is the one which advances.

• Intussuscipiens- is the one which receives (outer sheath)

• Intussusceptum- are the tube which advances (middle and inner sheath)

• Apex and inner tubes will have compromised blood supply which lead to gangrene.

    Ischaemia leads to sloughing off of the apex which in turn lead to bleeding which mixes with mucus to produce the classic currant jelly that is passed per anum.

    Gangrene may lead to perforation and peritonitis.

C/F

• Common at around 6 months.
• Sudden onset of pain ( screaming with drawing up of the legs vomiting, with passage of currant-jelly stool.
• It is recurrent.
• When it gets reduced, child becomes asymptomatic.
• On examination, a mass is felt on the left or right of the umbilicus which is sausage shaped with concavity towards umbilicus.
• Right iliac fossa is empty (Sign of dance)
• PR- Blood stained mucus maybe found on the finger.

          In extensive ileocolic and colocolic intussusception, the apex may be palpable or even protrude from the anus.

• If unrelieved, pain becomes continuous with abdominal distension and profuse vomiting.
• Ultimately small bowel obstruction or peritonitis secondary to gangrene may lead to death.

Investigations

• Plain x-ray abdomen

     Absent caecal gas shadow in ileoileal or ileocolic cases

• Barium enema

     Shows typical claw sign. (for ileocolic and colocolic)

• CT scan- maybe be done for ileoileal intussusception which shows small bowel mass.

D/D

• Acute enterocolitis
• HSP
• Rectal prolapse

T/T

• Ryles tube aspiration

• IV fluids

• Antibiotics

• Catheterization

• Surgery

     
Midline incision
     
Then reducing by squeezing the most distal part of the mass in cephalad direction.
     
In difficult cases- Cope’s method- little finger gently inserted into the neck of the intussusception and separation of adhesion is tried.
                             
Thumb and finger are placed in such a way to deinvaginate the apex.
                             
Gentle pressure is applied and gradually increased to reduce edema around the ileocaecal valve
       
In case of irreducible or gangrenous intussusception- mass excision.

Acute Abdomen and Appendicitis

The term acute abdomen refers to signs and symptoms of abdominal pain and tenderness, a clinical presentation that often requires emergency surgical therapy.

Nonsurgical Causes of Acute Abdomen

Endocrine and metabolic causes

• Uremia
• Diabetic crisis
• Addisonian crisis
• Acute intermittent porphyria
• Hereditary Mediterranean fever

Hematologic Causes

• Sickle cell crisis
• Acute leukemia
• Other blood dyscrasias

Toxins and Drugs

• Lead poisoning
• Other heavy metal poisoning
• Narcotic withdrawal
• Black widow spider poisoning

Surgical Acute Abdominal Conditions

Hemorrhage

• Solid organ trauma
• Leaking or ruptured arterial aneurysm
• Ruptured ectopic pregnancy
• Bleeding gastrointestinal diverticulum
• Arteriovenous malformation of gastrointestinal tract
• Intestinal ulceration
• Aortoduodenal fistula after aortic vascular graft
• Hemorrhagic pancreatitis
• Mallory-Weiss syndrome
• Spontaneous rupture of spleen

Infection

• Appendicitis
• Cholecystitis
• Meckel's diverticulitis
• Hepatic abscess
• Diverticular abscess
• Psoas abscess

Perforation

• Perforated gastrointestinal ulcerPerforated gastrointestinal cancer
• Boerhaave's syndrome
• Perforated diverticulum

Obstruction

• Adhesion related small or large bowel obstruction
• Sigmoid volvulus
• Cecal volvulus
• Incarcerated hernias
• Inflammatory bowel disease
• Gastrointestinal malignancy
• Intussusception

Ischemia:

• Buerger's disease
• Mesenteric thrombosis or embolism
• Ovarian torsion
• Ischemic colitis
• Testicular torsion
• Strangulated hernias

Acute Appendicitis

Etiology/Pathophysiology

• Obstruction of the lumen is the major cause. 
• Obstruction may be due to inspissated stool (fecalith or appendicolith), lymphoid hyperplasia, vegetable matter or seeds, parasites, or a neoplasm
• Obstruction of the appendiceal lumen contributes to bacterial overgrowth, and continued secretion of mucus leads to intraluminal distention and increased wall pressure.
• Luminal distention produces the visceral pain sensation experienced by the patient as periumbilical pain.
• Inflammation of the adjacent peritoneum gives rise to localized pain in the right lower quadrant.
• perforation typically occurs after at least 48 hours from the onset of symptoms and is accompanied

Diagnosis/ Clinical features

History

• Acute abdominal pain.
• The typical presentation begins with periumbilical pain (due to activation of visceral afferent neurons) followed by anorexia and nausea.
• The pain then localizes to the right lower quadrant as the inflammatory process progresses to involve the parietal peritoneum overlying the appendix.
• This classic pattern of migratory pain is the most reliable symptom of acute appendicitis.
• A bout of vomiting may occur, in contrast to the repeated bouts of vomiting that typically accompany viral gastroenteritis or small bowel obstruction.
• Fever ensues, followed by the development of leukocytosis.
• Occasional patients have urinary symptoms or microscopic hematuria, owing to inflammation of periappendiceal tissues adjacent to the ureter or bladder.
• Most patients with appendicitis develop an adynamic ileus and absent bowel movements on the day of presentation, occasional patients may have diarrhea.
• May present with small bowel obstruction related to contiguous regional inflammation.

Physical Examination

• Pt. look ill and  lie still in bed.
• Low-grade fever is common (∼38°C). 
• Examination of the abdomen usually reveals diminished bowel sounds and focal tenderness with voluntary guarding.
• The exact location of the tenderness is directly over the appendix, which is most commonly at McBurney's point (located one third of the distance along a line drawn from the anterior superior iliac spine to the umbilicus
• Peritoneal irritation can be elicited on physical examination by the findings of voluntary and involuntary guarding, percussion, or rebound tenderness.
• Pain in the right lower quadrant during palpation of the left lower quadrant (Rovsing's sign), pain on internal rotation of the hip (obturator sign, suggesting a pelvic appendix), and pain on extension of the right hip (iliopsoas sign, typical of a retrocecal appendix).
• Rectal and pelvic examinations are most likely to be negative. However, if the appendix is located within the pelvis, tenderness on abdominal examination may be minimal, whereas anterior tenderness may be elicited during rectal examination as the pelvic peritoneum is manipulated. Pelvic examination with cervical motion may also produce tenderness in this setting.

iliopsoas sign

Obturator Sign

Rovsing’s sign

Laboratory Studies

• The white blood cell count is elevated with more than 75% neutrophils.
• Shift to left.

Radiography

Ultrasonography

• appendix of 7 mm or more in anteroposterior diameter, a thick-walled, noncompressible luminal structure seen in cross section 
• In more advanced cases, periappendiceal fluid or a mass may be found.

Computed tomography (CT)

• Classic findings include a distended appendix greater than 7 mm in diameter and circumferential wall thickening, which may give the appearance of a halo or target .

Diagnostic Laparoscopy

• Although most patients with appendicitis will be accurately diagnosed based on history, physical exam, laboratory studies, and if necessary, imaging techniques, there are a small number in whom the diagnosis remains unclear.
• For these patients, diagnostic laparoscopy can provide both a direct examination of the appendix and a survey of the abdominal cavity for other possible causes of pain.

Shift to left

Treatment

• Most patients with acute appendicitis are managed by prompt surgical removal of the appendix.
• A brief period of resuscitation is usually sufficient to ensure the safe induction of general anesthesia.
• Preoperative antibiotics cover aerobic and anaerobic colonic flora. For patients with nonperforated appendicitis, a single preoperative dose of antibiotics reduces postoperative wound infections and intra-abdominal abscess formation.
• For patients with perforated or gangrenous appendicitis, we continue postoperative intravenous antibiotics until the patient is afebrile. 

Open appendectomy 

• Transverse right lower quadrant incision (Davis-Rockey) or an oblique incision (McArthur-McBurney), Recently-Lanz incision, Rutherford Morison incision- ( Para and retrocaecal or fixed appendix)
• For uncomplicated cases - transverse, muscle-splitting incision lateral to the rectus abdominis muscle over McBurney's point.
• After the peritoneum is entered, the inflamed appendix is identified by its firm consistency and br the presence of taeniae coli.
• The meso-appendix is divided between clamps and tied.
• A heavy absorbable tie is placed around the base of the appendix clamped and divided.
• An absorbable purse-string suture or Z stitch is placed into the cecal wall, and the appendiceal stump is inverted into a fold in the wall of the cecum. 

Division of  Mesoappendix

• Ligation of the baseand division of the appendix,

Placement of purse-string suture or Z stitch, Inversion of the appendiceal stump.

Laparoscopic appendectomy

•  A 10-mm port into the umbilicus, followed by a 5-mm port in the suprapubic midline region and a 5-mm port midway between the first 2 ports and to the left of the rectus abdominis muscle.
• With the patient in Trendelenburg's position and rotated left-side down, then gently sweep the terminal ileum medially and follow the taeniae of the cecum caudad to locate the appendix, which is then elevated. The mesoappendix is divided.
• Appendix is encircled with two heavy absorbable Endoloops cinched down at the base of the appendix and then a third Endoloop is placed about 1 cm distally and the appendix divided.

• Location of port sites 
  

  for laparoscopic 

  Appendectomy

  
  
  
  

• Division of the 
  

  mesoappendix 

  
  
  
  

• Placement of an 
  

  Absorbable 

  Endoloop encircling 

  the base of the 

  appendix

  
  
  

• Division of the 
  

  appendix between 

  Endoloops

  
  
  
  

Complication

• Ruptured appendix 
• Peritonitis and 
• Abscess

DNA REPLICATION AND REPAIR

The process of DNA duplication is usually called Replication.

The replication is termed “Semiconservative” since each new cell contains one strand of original DNA and one newly synthesized strand of DNA. The original polynucleotide strand of DNA serves as a template to guide the synthesis of the new complementary polynucleotide of DNA.

In a cell, DNA replication begins at specific locations in the genome, called "origins of replication.”

STEPS OF DNA REPLICATION

TELOMERES

• Repetitive sequences at the ends of the linear DNA molecule in eukaryotic chromosomes.
• With each round of replication, these are shortened because DNA polymerase can’t complete synthesis of 5’ end of the each strand.
• This contributes to aging of the cells.

TELOMERASE

      

      

• An enzyme in eukaryotes used to maintain the telomeres.

      

• Has telomerase reverse transcriptase activity.

      

• Present only in embryonic cells, germ cells (reproductive) and stem cells.

SIGNIFICANCE OF TELOMERASE

Cancer cells have high levels of telomerase which prevents telomeres from being short and contribute to immortality of malignant cells.

REVERSE TRANSCRIPTASE

RNA dependant DNA polymerase

Requires RNA template to direct the synthesis of new DNA.

Retroviruses (HIV) have this activity.

COMPARISION OF DNA & RNA SYNTHESIS

DNA REPAIR

Can be damaged by chemicals or radiation

Incorrect bases can also be incorporated during replication.

Multiple repair systems have evolved, allowing cells to maintain the sequence stability of their genomes.

     

1. Excision Endonuclease

     

2. Uracil glycosylase

     

3. AP endonuclease

REPAIR OF THYMINE DIMER

REPAIR OF DEAMINATED & MISSING BASES

Cytosine can become deaminated spontaneously by reaction with nitrous acid to form Uracil

Difference between Inguinal Hernias

Herniation of abdominal viscera can occur in one of several weak aspects of the abdominal wall (e.g. inguinal,femoral , umbilical, or diaphragmatic). Inguinal hernias are the most common of the abdominal hernias and occur more frequently in males due to the inherent weakness of the male inguinal canal. Inguinal hernias occur superior to the inguinal ligament. 

Two types of Inguinal hernias are described :

Indirect inguinal hernias: Indirect hernias result when abdominal contents protrude through the deep inguinal ring lateral to the inferior epigastric vessels. After passing through the inguinal canal and superficial ring, the viscera can  continue and coil in the scrotum. Indirect hernias follow the route taken by the testis and are found with in the spermatic cord. They are covered by the three layers of spermatic fascia.

Direct inguinal hernias: During a direct inguinal hernia, the abdominal contents will protrude through the weak area of the posterior wall of the inguinal canal medial to the inferior epigastric vessels (in the inguinal [Hesselbach's triangle]). Direct hernias rupture through the posterior wall of the inguinal canal and area usually found on the surface of the spermatic cord and bulge at the superficial ring. They may be covered by only the external layer of spermatic fascia.

Note: 

• That both Direct and Indirect hernias may exit through the superficial ring but only Indirect hernias pass through the deep ring.

• Direct hernias are found medial to the inferior epigastric vessels, and Indirect hernias occur lateral to the inferior epigastric vessels.

Clinical correlate

• Inguinal (Hasselbach's) Triangle : 

Direct inguinal hernias usually pass through it

Lateral border: Inferior epigastric vessels

Medial border: Rectus abdominis muscle

Inferior border: Inguinal ligament

• A persistent process vaginalis often results in a congenital indirect inguinal hernia.

• A collection of serous fluid in the tunica vaginalis form a hydrocele resulting in an enlarged scrotum. A hydrocele does not reduce in size when the patient is lying down.

• Inguinal hernias pass above the inguinal ligament 

• Femoral hernias pass below the inguinal ligament.

Femoral hernias: most often occur in women,

TRANSCRIPTION & RNA PROCESSING

TRANSCRIPTION

• Formation of the base sequence of a single stranded molecule of RNA from the base sequence of a dsDNA molecule.
• Only one strand of DNA molecule (i.e, template strand) is copied by RNA polymerase as it synthesize RNA in 5’ to 3’ direction for any particular gene.
• RNA product is antiparallel & complementary to the template strand.
• RNA polymerase recognizes start signals (promoters) and stop signals (terminators).

TYPES OF RNA

Ribosomal RNA (rRNA): most abundant used as structural component of the ribosome associates with ribosomal     proteins to form the complete, functional ribosome.

Transfer RNA (tRNA): second most abundant RNA carry amino acids to the ribosome during protein synthesis.

                                        

Messenger RNA (mRNA): carries information specifying  the amino acid sequence of a protein to the ribosome.Only type of RNA that is translated. 

                                               

Heterogeneous nuclear RNA (hnRNA): found only in the nucleus of the eukaryotic cells.Precursors of mRNA, formed during posttranscriptional processing.

                                                                   

Small nuclear RNA (snRNA): found in eukaryotic nucleus major functional is to participate in splicing mRNA (removal of introns)

Ribozymes: RNA molecules with enzymatic activity. 

Found both in prokaryotes & eukaryotes.

CONCEPTS AND TERMINOLOGY : TRANSCRIPTION

RNA is synthesized by a DNA dependant RNA polymerase.

RNA polymerase locates gene in DNA and binds the promoter site. No primer is required.

RNA polymerase moves along the template strand in the 3’ to 5’ direction as it synthesizes the RNA product in the 5’ to 3’ direction. The RNA product is complementary and antiparallel to the template strand. Coding strand is identical in sequence to RNA product except that RNA contains U instead of T in DNA.

The numbering system is used to identify the location of important bases. The 1st base transcribed as RNA is defined as the +1 base of that gene region. To the left (upstream) of it, bases are -1,-2,-3,etc. To the right (downstream) are +1,+2,+3,etc.

Transcription ends when RNA polymerase reaches a termination signal.

RNA Polymerases 

Production of Prokaryotic mRNA

• The mRNA produced by the gene is a monocistronic in the given figure. That is, it is transcribed from a single gene and codes for only a single protein.
• Some bacterial operons produce polycistronic messages. The mRNA in this case contains information from several genes and codes for several different proteins.

Production of Eukaryotic RNA

Processing of Eukaryotic mRNA

• Alternative Splicing of Eukaryotic mRNA
• For some genes, the primary transcript is spliced differently to produce two or more types of a protein from same gene k/a alternative splicing. E.g : Troponin (T, C, I) Immunoglobulins.

Ribosomal RNA

Transfer RNA (tRNA)

The important regions in tRNA are:

 1. Acceptor arm: appropriate AA is attached.

 2. Anticodon arm: recognizes a specific codon ( for the AA it carries) in mRNA.

The CCA tail is a cytosine-cytosine-adenine sequence at the 3' end of the tRNA molecule. This sequence is important for the recognition of tRNA by enzymes and critical in translation.

Structure of tRNA

Summary: