Clinical Drops - Embryology PDF

Clinical drops – Embryology Teratoma - Type of germ cell tumour - Includes components and tissues derived from all 3 embryonic layers - Can be extragonadal or gonadal - Derived from PGCs = totipotency (ability to form all cell types) - Usually occur in the ovaries of women and testes...

Clinical drops – Embryology Teratoma - Type of germ cell tumour - Includes components and tissues derived from all 3 embryonic layers - Can be extragonadal or gonadal - Derived from PGCs = totipotency (ability to form all cell types) - Usually occur in the ovaries of women and testes of men Down syndrome - Non-disjunction during meiosis - 2 copies of chromosome 21 fail to separate during first or second meiotic anaphase - Results in trisomy 21 embryo Male infertility - Number is less than 10 million per ml - Factors affecting sperm motility o Environmental toxins o Radiation o Hyperthermia o Phycological stress o Genetic disorder o Mitochondrial abnormalities o Lifestyle factors o Smoking Mittelschmerz - One-sided, lower abdominal pain associated with ovulation - Hormonal changes lead to muscle contractions - Variable amount of abdominal and pelvic pain Ectopic pregnancy - Fertilized egg implants and grows outside the main cavity of the uterus - Leads to uterine tube rupture and haemorrhage - Present with internal bleeding, pelvic pain, low bac pain - Risk factors o Pelvic inflammatory disease – scar tissue in the uterine tubes o Endometriosis o Smoking – cilia of the uterine tube are affected Spontaneous abortion or miscarriage - Pregnancy loss that occurs naturally before the 20th week of gestation - Most common during the 3rd week post fertilisation - Most commonly due to chromosomal abnormalities Sirenomelia - Fusion of lower 2 limbs at the midline - Incidence of 1 in 100 000 births with a male predominance - Linked to maternal gestational diabetes - Insufficient development of the caudal mesoderm – lower limbs and urogenital system Chordomas - Maligant cancers that develop from remnants of the notochord  - Found at o Base of skull o Vertebral column - Slow growth and only discovered when large – compressing brain and spinal structures Holoprosencephaly - Occurs in the first two or three weeks of pregnancy - results in abnormal development of the brain - Due to alterations of genes expressed on the midline - Failure of activation of hox genes - Defect in the activation of SHH pathway - Linked to ethanol (teratogen) Sacrococcygeal teratomas - Remnants of the primitive streak - Most common tumour of childhood - Become malignant in infancy - Removed by 6 months Situs inversus - Mirror-image transposition of both the abdominal and the thoracic organs - Due to anomalies in the ciliary movement at the primitive node - Mutation in the Lrd gene Kartagener syndrome - Autosomal recessive genetic ciliary disorder - Includes: o Situs inversus o Chronic sinusitis o Bronchiectasis - Due to defective movement of cilia - Mutations in dynein genes and deficiency in ciliary dynein arms Congenital diaphragmatic hernia - Due to defects of diaphragm formation - Pleural cavity and peritoneal cavity communicate - Inhibition of development and inflation of the lungs - Most common cause of pulmonary hypoplasia - Polyhydramnios may be present Thalidomide and birth defects - Thalidomide was used to combat morning sickness - Malformation of the forelimbs is drug was started in the 4th week - Malformation of the hindlimbs if drug was started in the 5th week Synpolydactyly - Fusion of digits or presence of additional fingers or toes - Caused by mutations in HOX gene Thalassemia - Inherited blood disorder affecting the haemoglobin genes - Resulting in ineffective erythropoiesis - Alpha thalassemia = reduced or absent synthesis of alpha globin chains  - Beta thalassemia = reduced or absent synthesis of beta globin chains Disorders of amniotic fluids: Oligohydramnios - Decreased amniotic fluid volume for gestational age (at 36 weeks, should be 1000ml) - Causes o Diminished placental blood flow o Preterm rupture of amniotic membrane o Renal agenesis o Urinary tract obstruction - Fetal complications o Pulmonary hypoplasia o Growth restrictions = deformations o Facial distortion - Linked to Potter syndrome (bilateral renal agenesis) - pulmonary hyperplasia, limb deformities, facial abnormalities and wrinkled skin Disorders of amniotic fluids: Polyhydramnios - Increased amniotic fluid volume for gestational age - Causes – somewhat unknown - Maternal factors o Maternal diabetes o Cardiac problems o Infections - Fetal factors o Oesophageal or duodenal atresia o Anencephaly = Absence of brain (no capacity to swallow) - Often associated with defects of the CNS (spina bifda) - Increased risk of complications o Preterm contractions and preterm labour o Premature rupture of membranes o Placental abruption o Fetal malposition o Umbilical cord prolapse o Post partum haemorrhage o Fetal death Amniotic bands - Fetal malformations associated with fibrous bands that entangle or entrap various fetal parts in utero - Lead to deformation, malformation, or amputation of portion of the body Transmission of pathogens to the fetus - Placenta is fairly impermeable to microorganisms, but some viruses and bacteria can cross it - Toxoplasmosis - Others (Syphilis, Hepatitis B) - Rubella - Cytomegalovirus - Herpes simplex virus Pathological placentas: Placenta accreta - Abnormal invasion of placental trophoblasts into the uterine myometrium - With partial or complete absence of the decidua basalis - Normal pregnancy and birth but if the placenta fails to detach – attempt at removal may cause haemorrhage Pathological placentas: Placenta increta - The placenta attaches itself even more deeply into the muscle wall of the uterus Pathological placentas: Placenta percreta - Complete penetration of the myometrium to reach the perimetrium - Can result in attachment to bladder and rectum - Caesarean and hysterectomy immediately after birth Pathological placentas: Placenta previa - Attachment at the level of the internal uterine os - Blood vessel rupture during late pregnancy = third trimester bleeding - Mother may bleed to death - Fetus may suffer from reduced blood supply - Caesarean section necessary Placental abruption - Placenta separates prematurely from the inner wall of the uterus before birth - Causes o Trauma o Smoking o Hypertension o Preeclampsia o Use of drugs - Abrupt and painful bleeding in third trimester - Maternal shock - Fetal distress Vasa previa - When the umbilical (fetal) blood vessels abnormally travel through the amniochorionic membrane before reaching the placenta proper - If the umbilical blood vessels cross the internal os = vasa previa - If one of the fetal blood vessels ruptures during pregnancy, labor, or delivery, the fetus will bleed to death Choriocarcinoma - Gestational trophoblastic disease - Occurs due to excessive proliferation and invasion of cytotrophoblast cells - Cells have combined marked propensity to invade blood vessels = go to liver - Elevated hCG levels are diagnostic - Prognosis is poor if it spreads to the liver or brain Hydatiform mole - Fetus is entirely missing, and the conceptus consists only of placental membranes - Because the fetal vasculature that would normally drain the fluid taken up from the maternal circulation is absent, the placental villi of a complete mole are swollen and vesicular  - Complete moles often abort early in pregnancy - If they do not abort, the physician may discover them because they result in vaginal bleeding, especially during the 6th to 6th weeks of pregnancy - Cause excessive nausea and vomiting due to high hCG - Complete mole can have a normal, diploid karyotype - all chromosomes are derived from the father – arises in 2 ways: o Dispermic fertilization = two spermatozoa may fertilize an oocyte that lacks (or loses) its own nucleus and the two male pronuclei may then fuse to form a diploid nucleus o Monospermic fertilization = single spermatozoon inseminates an oocyte that lacks (or loses) its own nucleus, the male pronucleus may undergo an initial mitosis (doubling its DNA) without cytokinesis Clinical drops – Organogenesis Esophageal stenosis - Lumen of the esophagus is narrowed - May be caused by o Submucosal/muscularis externa hypertrophy o Remnants of the tracheal cartilaginous ring within the wall of the esophagus o Membranous diaphragm obstructing the lumen - due to incomplete recanalization - Fetuses cannot swallow the amniotic fluid = polyhydramnios - Newborn has difficulties in swallowing milk = Regurgitation and choking Esophageal atresia - Tracheoesophageal septum deviates too far dorsally, causing the esophagus to end as a closed tube - 33% are associated to other congenital defects associated with the VATER syndromes o Vertebral defects o Anal atresia o Tracheoesophageal fistula o Renal defects Tracheoesophageal fistula - Abnormal connection between trachea and esophagus - Resulting from failure of foregut to separate completely into trachea and esophagus - 1 – 3000 to 5000 births - Allow milk to be aspirated into lungs = choking Heterotopic gastric mucosa - Mature gastric tissue in location where it is not normally found - Discrete small nodules or polyps that can occur in duplication or diverticula - May cause obstruction, diarrheal, ulceration, bleeding (from digestion of mucosa), perforation and intussusception Pyloric stenosis - Occurs when the muscularis externa in the pyloric region hypertrophies and forms a narrow pyloric lumen that obstructs food passage - Projectile, nonbilious vomiting after feeding  - Due to inability of the pyloric sphincter to relax due to a faulty migration of neural crest cells so that the ganglion cells of the enteric nervous system are not properly populated Duodenal atresia - 3rd most common atresia of the GI tract - Defective vacuolization leading to incomplete recanalization - Prenatally = polyhydramnios - Postnatally = bilious vomit - Present with double bubble sign - Associated with Down syndrome (25-40%) Annular pancreas - Occurs when the ventral pancreatic bud fuses with the dorsal bud both dorsally and ventrally, forming a ring of pancreatic tissue around the duodenum a - Causing severe duodenal obstruction - Newborns have bilious vomit and feeding intolerances - Also causes double bubble effect Ectopic pancreas - Location of pancreatic tissue in o Stomach o Duodenum o Jejunum o Ileal diverticulum of Meckel - Usually asymptomatic - May cause gastrointestinal bleeding, obstruction, and cancer Biliary atresia - Obliteration of extrahepatic and/or intrahepatic ducts - Ducts are replaced by fibrotic tissue due to acute and chronic inflammation. - Clinical features o Progressive neonatal jaundice with onset soon after birth o White clay-colored stool o Dark-colored urine - 12–19-month average survival time with 100% mortality rate - Treated with liver transplantation Malrotation and abnormal fixation of midgut - Occurs when the midgut loop undergoes only partial counterclockwise rotation - Results in the cecum and appendix lying in a subpyloric location and the small intestine suspended by only a vascular pedicle (not a broad mesentery) - Major clinical complication = volvulus o Twisting of the small intestines around the vascular pedicle o Can cause necrosis due to compromised blood supply - Associated to bilious vomit, chronic abdominal pain, gastroesophageal reflux - Variations: incomplete rotation, non-rotation, and revered rotation Obstructing Ladd’s bands - Fibrous stalk of peritoneal tissue that attach the cecum to the retroperitoneum - Cecum is found in the upper right quadrant instead of lower right  - Ladd’s bands pass over the second part of the duodenum causing extrinsic compression and obstruction - Postnatally = poor feeding, bilious vomit - Associated to malrotation of intestines Meckel’s diverticulum - Occurs when a remnant of the vitelline duct persists, thereby forming an outpouching located on the border of the ileum - The outpouching may connect to the umbilicus via a fibrous cord or fistula - Heterotopic gastric mucosa may be present, which leads to ulceration and perforation Congenital omphalocele - Herniation of the bowel and other visceral organs through the umbilical ring – which is covered by a thin avascular membrane that may rupture o Can be a large herniation consisting of the entire bowel and liver with the umbilical cord inserting into the apex of the omphalocele - Failure of the midgut loop to re-enter the abdominal cavity during the 10th week - Associated with chromosome abnormalities Umbilical hernia - Small protrusion of bowel through the umbilical ring – which is covered by skin o The intestine returns normally into the body cavity, but part of the musculature of the abdominal wall (rectus muscle) fails to close around the umbilical ring - Apparent when an infant cries or strains - Close spontaneously by 5 years of age Gastroschisis - Defect of the anterior abdominal wall in which the bowel protrudes without a covering sac between the developing rectus muscles, just lateral to the umbilicus (mostly to the right) o Supposedly due to premature obliteration of the right umbilical vein – which might create a localised right-sided body wall weakness (due to localised ischemia) - Organs are exposed to amniotic fluid, and become thickened and covered with adhesions - The umbilical ring closes (unlike in omphalocele) – and herniation occurs due to a weakening in the body wall - Isolated and has no known associated chromosomal abnormalities Anorectal abnormalities - Imperforate anus = the anorectal canal forms properly but the anal membrane separating the ectodermal and endodermal portions of the anus is abnormally thick leading to a failure of rupturing and an incomplete rupturing o May form rectovaginal fistula, rectourethral fistula o May cause rectal atresia  - Lead to defective or absent meconium o Meconium = Earliest stool of mammalian infant o Composed of materials ingested during the uterine life: intestinal cells, lanugo, mucus, amniotic fluid, bile, water o Viscous and sticky like tar – dark green and odourless o Has to be checked that it is coming from the anal canal Hirsprungs disease - Congenital disorder defined by the absence of ganglion cells at the Meissner's plexus of the submucosa and Auerbach's plexus of the muscularis in the terminal rectum that extends in a variable distance proximally - 1 in 5,000 live births - As enteric neurons are essential for the propulsion of gut contents, this leads to abnormal dilation or distention of the colon o And increased wall thickness due to muscular hypertrophy in the intestine proximal to the aganglioic segment - Symptoms include: o Enlarged bowel caused by the obstruction and lack of peristalsis o Delay in the passage of meconium o Constipation o Vomiting o Abdominal pain o Distension - Can become life threatening and develop into intestinal infections (enterocolitis) and rupture of the cecum - Removal of constricted segment is the only effective treatment - Typically an isolated and sporadic event, though has been linked to trisomy 21 in 15% of cases Cleft palate / lip - The face is created by the growth and fusion of five facial swellings - complete or partial failure of fusion between any of these swellings results in a facial cleft - Cleft lip = results from failure of the maxillary prominence and medial nasal processes to join together - Cleft palate = results from failure of the two palatal shelves to fuse with each other along the midline - Anterior cleft palate occurs when the palatine shelves fail to fuse with the primary palate - Posterior cleft palate occurs when the palatine shelves fail to fuse with each other and with the nasal septum - Anteroposterior cleft palate occurs when there is a combination of both defects - Facial clefts can affect feeding, speech, hearing, and social integration - 1 out of 5 cleft palate is inherited - Environmental factors o Rubella and other infections o Medications (anticonvulsants) o Alcohol and drug use o Cigarette smoke o Lack of vitamins during pregnancy (folic acid) Thyroglossal duct remnants - Occurs when parts of the thyroglossal duct persist and form a cyst - Most commonly located in the midline near the hyoid bone - Sometimes forms near the tongue = inguinal cyst Treacher Collins syndrome - Results from abnormal development of pharyngeal arch 1 - Produces facial abnormalities - Caused by a lack of migration of neural crest cells into pharyngeal arch 1 - Autosomal dominant genetic disorder caused by a mutation in the TCOF1 gene on chromosome 5q32-q33.1 - Clinical features: o Hypoplasia of the zygomatic bones and mandible = resulting in midface hypoplasia o Micrognathia (underdeveloped jaw) o External ear abnormalities DiGeorge syndrome - Caused by a microdeletion of a region in chromosome 22q11.2 - Results in the failure of pharyngeal pouches 3 and 4 to differentiate into the thymus and parathyroid glands - Accompanied by facial anomalies resembling first arch syndrome - Cardiovascular defects - Abnormal face - Thymic hypoplasia - Cleft palate - Hypocalcaemia Pharyngeal cysts - Occurs when parts of the pharyngeal grooves 2, 3, and 4 (or pouches) that are normally obliterated persist = forming a cyst - Generally found near the angle of the mandible - Cyst = completely enclosed cavity - Sinus = closed on one end open to the outside or pharynx - Fistula = Epithelial lined tube open at both ends Respiratory distress syndrome / Hyaline membrane disease - Caused by a deficiency or absence of surfactant that is produced by type II pneumocytes (surfactant is a surface active agent that coats the inside of alveoli to maintain alveolar patency) - Prevalent in premature infants (accounts for 50%–70% of deaths in premature infants), infants of diabetic mothers, infants who experienced fetal asphyxia or maternofetal hemorrhage (damages type II pneumocytes), and multiple- birth infants - Clinical features: o Dyspnea o Tachypnea o Inspiratory retractions of chest wall o Expiratory grunting o Cyanosis o Nasal flaring - Treatments:  o Administration of corticosteroid to mother several days before delivery - to increase surfactant production o Postnatal administration of an artificial surfactant solution, and postnatal high- frequency ventilation - Can cause germinal matrix hemorrhage o Contains a rich network of fragile, thin-walled blood vessels o The brain of the premature infant lacks the ability to autoregulate the cerebral blood pressure = increased arterial blood pressure in these blood vessels leads to rupture and hemorrhage into the germinal matrix o Causes neurological sequelae = cerebral palsy, mental retardation, and seizures Congenital bronchogenic cyst - Abnormality in bronchial branching and found within the mediastinum or intrapulmonary - Found in o Anterior mediastinum o Along the tracheobronchial tree o Intrapulmonary o Pericardium - Contain fluid = appear as water-density masses on chest radiographs - May present with infection – mostly incidental findings Bronchiectasis - Abnormal, permanent dilatation of bronchi due to: o Chronic necrotizing infection = Staphylococcus, Streptococcus, Haemophilus influenzae o Bronchial obstruction o Congenital conditions = Kartagener syndrome, cystic fibrosis, immunodeficiency disorders) - The lower lobes of the lung are predominately affected, and the affected bronchi have a saccular appearance - Clinical features: o Cough o Fever o Expectoration of large amounts of foul-smelling purulent sputum Congenital pulmonary airway malformation - Results from a proliferation of terminal bronchiolar structures with associated suppression of alveolar growth - Abnormalities in bronchial branching - Cysts filled with fluids - Communication with bronchial tree - Symptoms: o Shortness of breath o Fever o Cough Congenital lobar emphysema - Characterized by progressive overdistention of one of the upper lobes or the right middle lobe with air - No destruction of alveolar walls - Air can be inspired through collapsed bronchi but cannot be expired - Due to failure of cartilage development - External or internal bronchial obstruction - During the first few days of life, fluid may be trapped in the involved lobe Pulmonary hypoplasia - Poorly developed bronchial tree with abnormal histology - Involves the right lung in association with right-sided obstructive congenital heart defects - In association with congenital diaphragmatic hernia - compresses the developing lung - In association with bilateral renal agenesis (Potter syndrome) - causes an insufficient amount of amniotic fluid (oligohydramnios) to be produced which in turn increases pressure on the fetal thorax Renal agenesis - Occurs when the ureteric bud fails to develop - eliminating the induction of metanephric vesicles and nephron formation - 2 types: o Unilateral renal agenesis is relatively common (more common in males) - it is asymptomatic and compatible with life because the remaining kidney hypertrophies o Bilateral renal agenesis is relatively uncommon - causes oligohydramnios, which causes compression of the fetus, resulting in Potter syndrome (deformed limbs, wrinkly skin, and abnormal facial appearance) Renal fusion - The most common type of renal fusion is the horseshoe kidney - Occurs when the inferior poles of the kidneys fuse across the midline - Normal ascent of the kidneys is arrested because the fused portion gets trapped behind the inferior mesenteric artery - Kidney rotation is also arrested, so that the hilum faces ventrally Congenital polycystic kidney disease – Autosomal recessive - Paediatric onset (children = recessive) - Linked to chromosome 6 o Defective coding of fibrocystin - Kidneys are huge and spongy and contain numerous cysts due to the dilation of collecting ducts and tubules, which severely compromises kidney function - Associated clinically with cysts of the liver, pancreas, and lungs - Leads to renal failure in infancy or adolescence Congenital polycystic kidney disease – Autosomal dominant - Adult onset (= dominant) - Mutation of genes coding for polycystin 1 and 2 - Cysts in different potions of the kidney, liver, pancreas, testis and ovary  - Slower evolution - Renal failure in adult age Congenital hydronephrosis - Ureter obstruction - Dilation of the pelvis and calyxes - Decrease in thickness of cortex - Bending of junction between pelvis and ureter Wilms tumor - Most common renal malignancy of childhood - The tumor recapitulates different stages of embryological formation of the kidney, so that three classic histological areas are described: o Stromal o Blastemal area of tightly packed embryonic cells o Tubular area - Due to genetic alterations that deal with the normal embryological development of the genitourinary tract - Genetic markers (gene alterations) o WT1 o CTNNB1 o WTX - Median age of diagnosis is 3.5 years - 80-90% of children survive - Signs and symptoms: o Asymptomatic abdominal mass o Abdominal pain o UTI o Hypertension o Fever Exstrophy of the bladder - Occurs when the posterior wall of the urinary bladder is exposed to the exterior - Caused by a failure of the anterior abdominal wall and anterior wall of the bladder to develop properly - Due to a problem in the migration of the mesoderm between the ectoderm and the endoderm - Associated clinically with urine drainage to the exterior and epispadias Epispadias - Occurs when the external urethral orifice opens onto the dorsal surface of the penis Urachal fistula or cyst - Occurs when a remnant of the allantois persists forming fistula or cyst - It is found along the midline on a path from the umbilicus to the apex of the urinary bladder - Fistula forms a direct connection between the urinary bladder and the outside of the body at the umbilicus, causing urine drainage from the umbilicus Uterine anomalies - Unicornuate uterus = Occur when one paramesonephric duct fails to develop or incompletely develops - Bicornuate uterus = Occur when there is partial fusion of the paramesonephric ducts Inguinal hernia - Occurs when a large patency of the processus vaginalis remains so that a loop of intestine may herniate into the scrotum or labia majora - Most common in males and is generally associated with cryptorchidism - Direct = Budge through weakened fascia, directly being the superficial inguinal ring - Indirect = Traverses inguinal canal (same course as spermatic cord) Cryptorchidism Testicular hydrocele - Occurs when a small patency of the processus vaginalis remains so that peritoneal fluid can flow into the processus vaginalis - Results in a fluid-filled cyst near the testes Patent oval foramen - Incomplete adhesion of the septum primum (valve of the foramen ovale) with the septum secundum - Causes shunting of blood from left atrium to right atrium Ostium secundim defect - Excessive resorption of septum secundum - Does not cover foramen secundum - Generally asymptomatic but persistent increase in flow to the right atrium may lead to enlargement of the right atrium and ventricle – debilitating atrial arrythmias - Causes pulmonary hypertension over time – leading to heart failure  - Compatible with life until the pressure in the right atrium is greater than that in the left atrium = reversal of the shunt and cyanosis Ventricular septal defects - Most frequent congenital defect (25% of all cardiac abnormalities) - Can come from several causes o Deficient development of the proximal outflow tract cushions o Failure of the muscular and membranous ventricular septal components to fuse o Failure of the dorsal and ventral endocardial cushions to fuse o Insufficient development of the muscular ventricular septum o Altered hemodynamics - Leads to left to right shunting of blood = increased blood flow to the pulmonary circulation (pulmonary hypertension) Tetralogy of Fallot - Most common cyanotic congenital malformation due to a defect in the septation of the truncus arteriosus that favours the aorta - Causes a defect in the superior portion of the interventricular septum - Defect in migration of neural crest cells - Results in a condition in which the pulmonary trunk exhibits a small diameter and the aorta exhibits a large diameter - Characterized by PROVE: o Pulmonary stenosis o Right ventricular hypertrophy o Overriding aorta o Ventricular septal defect - Clinically associated with marked cyanosis Coarction of the aorta - Typically a birth defect in which a part of the aorta is narrower than usual - Can burst and lead to haemorrhage, stroke and heart failure Clinical drops – Organ structure Atherosclerosis - Thickening or hardening of the arteries caused by a buildup of plaque in the inner lining of an artery - Initiated by endothelial dysfunction accompanied by low-density lipoprotein retention and its modification in the tunica intima - Modified lipids promote the activation of endothelial cells, leading to monocyte recruitment within the tunica intima - Lipoproteins are captured by differentiated monocytes and vascular smooth muscle cells, which promote foam cell formation  - Several inflammatory signalling pathways are activated due to the fatty streak formation, which represents the first sign of atherosclerosis = characterized by an accumulation of lipids both within the cells (macrophages and vascular smooth muscle cells) and the extracellular media Aneurysm - Abnormal swelling or bulge in the wall of a blood vessel o Due to mechanical force from blood pressure - Displacement of elastic fibres by collagen fibres - Related to o High blood pressure o Atherosclerosis o Smoking o Older age o Alcohol use - Also associated to connective tissue disorders o Marfan syndrome (inability to produce fibrillin) o Ehlers dalos syndrome (heritable disorders of connective tissue comprising mutations in the genes involved in the structure and/or biosynthesis of collagen) Dissection of the aorta - A tear occurs in the inner layer of the body's main artery (inner most layer) - Blood rushes through the tear, causing the inner and middle layers of the aorta to split (dissect) - In the channel which is blind-ended, if it gets bigger, it can push on other branches of larger blood vessels o Can narrow other branches and reduce blood flow through them - May also cause abnormal widening or ballooning of the aorta aneurysm Endothelial cells and COVID19 - COVID-19 affects the vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction and multi-organ injury - Infection can cause: o Reduced nitric oxide (NO) bioavailability o Oxidative stress o Endothelial injury o Glycocalyx/barrier disruption o Hyperpermeability o Inflammation/leukocyte adhesion o Endothelial-to-mesenchymal transition o Hypercoagulability Clinical drop: Varicose veins - Twisted and abnormally tortuous (twisted) veins most commonly located on the lower extremities - Pathophysiology: o Genetic predisposition o Incompetent valves o Weakened vascular walls  o Increased intravenous pressure - Risk factors: o Family history of venous disease o Female sex o Older age o Chronically increased intra-abdominal pressure due to obesity, pregnancy, chronic constipation, or a tumour o Prolonged standing Edema - Swelling of soft tissue due to abnormal expansion of interstitial fluids volume - Edema fluid = plasma transudate that accumulates when movements of fluids from vascular to interstitial spaces is favoured - Localised edema – usually due to venous or lymphatic obstruction - Generalised edema – usually of cardiac or renal origin - Lymph transport can be impaired because of a hypoplastic initial lymphatic capitally network – because of abnormal coverage of lymphatic capillaries o These capillaries have basement membrane components (which should be discontinuous) and lack functioning lymphatic valves - Defecting lymph drainage leads to tissue fibrosis and fat deposition caused by abnormal local chronic inflammatory responses Shock - State of cellular and tissue hypoxia due to either reduced oxygen delivery, increased oxygen consumption, inadequate oxygen utilization, or a combination of these processes - Hypoperfusion induce imbalance between the delivery of and the requirements for oxygen lead to cellular dysfunction - Cellular injury causes: o Production of DAMPs and inflammatory mediators Esophageal varices - An increase in pressure in the portal venous system, caused by chronic liver disease, results in dilation of the submucosal venous sinuses and the formation of esophageal varices - Rupture of the varices or ulceration of the overlying mucosa can produce hemorrhage into the esophagus and stomach - Symptoms: o Gastrointestinal bleeding o Vomit with blood Reflux esophagitis - Inflammation of the esophageal mucosa secondary to gastroesophageal reflux disease - Can cause: o Ulceration o Difficulties in swallowing o Caudal stratified epithelium may be replaced by columnar epithelium – metaplasia and cancer Barret’s esophagus - Acquired disorder - Occurs due to severe esophageal mucosal injury caused by chronic gastroesophageal reflux - Characterized by the replacement of the normal esophageal squamous epithelium with an intestinal columnar epithelium that contains caliciform cells Achalasia - Oesophageal smooth muscle motility disorder that occurs due to a failure of relaxation of the lower oesophageal sphincter - Characterised by loss of enteric neurons leading to the absence of peristalsis - Causes a functional obstruction at the gastroesophageal junction - Symptoms: o Dysphagia o Regurgitation o Chest pain o Increased risk of oesophageal carcinoma - Aetiology is unclear, but suggested to be linked to autoimmune phenomenon, viral infection, and genetic predisposition Hiatal hernia - The upper part of the stomach bulges through an opening in the diaphragm - Type I (sliding type) when the gastroesophageal junction is displaced upwards towards the hiatus - Type II is a paraesophageal hiatal hernia, which occurs when part of the stomach migrates into the mediastinum parallel to the esophagus Pernicious anaemia - Caused by a vitamin B12 deficiency – parietal cells produce intrinsic factor that would normally absorb B12 - Characterized by a decrease in the production of red blood cells and the release into the blood circulation of large red blood cells (megaloblastic anemia) - Causes o Bacterial overgrowth in the small intestine o Parasitic tapeworm o Peptic ulcer disease o Gastrectomy o Long term us of H2 receptor antagonists Peptic ulcer disease - A breakdown of gastic microcirculation (which is a protective mechanism, including mucus and bicarbonate secretion) allows Helicobacter pylori infection, leading to peptic ulcer disease - Helicobacter pylori infection affects the integrity of the protective gastric mucus blanket, = enable the action of pepsin and HCl and of H - Characterized by a partial or total loss of the mucosal surface of the stomach or duodenum or both  - Stages of H. pylori infection o Active phase = H. pylori are highly motile, propelled by about six flagella. During this time, H. pylori decrease the acidity by producing ammonia (NH3) by the action of the enzyme urease o Stationary phase = H. pylori enter the mucus blanket and produce adhesins that attach to the apical surfaces of the surface mucous epithelial cells containing fucose- binding sites. Cell attachment enables adherent H. pylori to obtain nutrients from epithelial cells, which undergo necrosis. o Colonization phase = Well-nourished H. pylori detach from the mucus-secreting surface cells, replicate within the mucus blanket and attach to sialic acid– containing mucous proteins. Bacteria reenter the active phase and reinitiate their life cycle Rotavirus - Most common cause of diarrhoeal disease among infants and young children - Nearly every child in the world is infected with a rotavirus at least once by the age of five - Immunity develops with each infection, so subsequent infections are less severe - Adults are rarely affected - Destroys mature absorptive intestinal villus cells = resulting in loss of absorptive surface in the small intestine - Absorption of salt and water decrease = net fluid secretion and osmotic diarrhea - Peristaltic rush = whole intestine sweeps contents Diverticulosis - Condition characterized by the presence of small pouches (diverticula) that develop in the walls of the colon - Occur due to increased pressure within the colon, leading to the formation of small bulging pouches, often at weak points in the colon wall - Main causes: o Age-related weakening of the colon walls o Low-fiber diet - which can result in constipation and increased pressure in the colon o Genetics may play a role in predisposing some individuals to diverticulosis. - Symptoms: o Often asymptomatic o When symptoms do occur: abdominal pain, bloating, changes in bowel habits, and, in severe cases, complications such as diverticulitis or bleeding. Colon polyps - Abnormal growths in the lining of the colon or rectum, which may be noncancerous (benign) initially but have the potential to become cancerous over time - Typically form due to an overgrowth of cells in the lining of the colon or rectum - Causes: o Genetic factors and family history of colon polyps or colorectal cancer o Age o Inflammatory conditions (IBD) - Often asymptomatic - Some polyps may cause rectal bleeding and blood in the stool Haemorrhoids - Swollen veins in the rectum and anus that result in discomfort, bleeding, and sometimes protrusion during bowel movements - Develop when the veins in the rectum or anus become swollen due to increased pressure  - Causes: Straining during bowel movements, obesity, or pregnancy - Internal = above the pectinate line - External = below the pectinate line Liver fibrosis - Condition characterized by the excessive accumulation of fibrous tissue in the liver, often in response to chronic liver injury or inflammation - Results from prolonged liver damage, which triggers a wound-healing response leading to the deposition of collagen and other fibrous tissue, ultimately affecting the liver's structure and function - Causes: o Chronic viral hepatitis (such as hepatitis B or C) o Alcohol abuse o Certain genetic disorders affecting the liver - Symptoms: o Liver fibrosis itself may not present with noticeable symptoms. o As the condition progresses, it can lead to cirrhosis, which may cause fatigue, weakness, abdominal swelling, easy bruising, and other symptoms associated with impaired liver function Jaundice - Characterized by yellowing of the skin, eyes, and mucous membranes due to elevated levels of bilirubin in the blood - Occurs when there is an excess of bilirubin, produced during the breakdown of red blood cells, leading to its accumulation in the body tissues - Serum bilirubin is greater than 2mg/dL - Not a disease but rather a sign that can occur in many different diseases - Causes: o Liver diseases, such as hepatitis, cirrhosis, or liver cancer, which impair bilirubin processing o Hemolysis (breakdown of red blood cells), which can overwhelm the liver's capacity to eliminate bilirubin o Blockage or obstruction of the bile ducts, preventing the normal flow of bile and bilirubin Gallstones - Solid particles that form in the gallbladder, often composed of cholesterol or bilirubin, causing abdominal pain and potential complications - Develop when there is an imbalance in the substances that make up bile, leading to the formation of solid particles - Causes o Excess cholesterol in the bile o Imbalance in the components of bile, such as too much bilirubin o Reduced gallbladder emptying, allowing bile to become concentrated and form stones - May cause no signs or symptoms - If a gallstone lodges in a duct and causes a blaockage, the resulting signs and symptoms include: o Sudden intensifying pain in the upper right portion of the abdomen o Back pain between the shoulders o Nausea or vomiting o Jaundice if a stone blocks the bile duct Cough - A reflex driven by irritation and clogging of the airways  - 3 phases of cough: o Inspiratory phase = air is taken up into the lungs (2.5 3L) o Compressive phase = Glottis closes and intrathoracic pressure builds as a result of expiratory muscle contraction o Expiratory phase = sudden release of air at high velocity (20 – 500 mph) Cystic fibrosis - Autosomal recessive genetic disorder caused by mutations in the CFTR gene on chromosome 7q31.2 for the cystic fibrosis transmembrane conductance regulator o Functions as a chloride ion channel - Approximately 70% of the cases are in North America - Clinical features: o Production of abnormally thick mucus by epithelial cells lining the respiratory tract = resulting in obstruction of pulmonary airways o Recurrent respiratory bacterial infections o End-stage lung disease o Pancreatic insufficiency with malabsorption - Males are almost always sterile due to the obstruction or absence of the vas deferens Asthma - Chronic inflammatory disorder of the airways - Characterised by: o Hypersensitivity to various triggers o Reversible outflow obstruction o Bronchospasm - During an asthma attack, smooth muscle located in the bronchial tree of the lung constricts and decreases the flow of the air in the airways o Amount of airflow can be further decreased by inflammation or excess mucous secretions - Clinical symptoms: o Shortness of breath o Coughing o Wheezing o Chest tightness Emphysema - Caused by a permanent enlargement of the air spaces distal to the terminal bronchioles - Due to the progressive and irreversible destruction of elastic tissue of the alveolar walls - Elastic tissue in the interalveolar wall can be destroyed by: o Elastase released by neutrophils present in the alveolar lumen – caused by persistent stimulus which increases the number of neutrophils in the alveolar lumen o Serum 1-antitrypsin neutralizes elastase - Damaged elastic fibers cannot recoil when stretched = adjacent alveoli become confluent, producing large air spaces - The loss of elastic tissue also affects the wall of terminal and respiratory bronchioles  - Centroacinar / proximal acinar / centrilobar = Originates when the respiratory bronchioles are affected o The more distal alveolar duct and alveoli are intact o Emphysematous and normal air spaces coexist within the same lobule and acini - Panacinar / panlobar = blebs are observed from the respiratory bronchiole down to the alveolar sacs o More common in patients with a deficiency in the 1-antitrypsin gene encoding a serum protein o Protein 1-antitrypsin is a major inhibitor of proteases (elastase) secreted by neutrophils during inflammation o Under the influence of a stimulus, such as cigarette smoke, macrophages in the alveolar wall and alveolar lumen secrete proteases and chemoattractants to recruit neutrophils o Chemoattracted neutrophils appear in the alveolar lumen and wall and release elastase, normally neutralized by 1-antitrypsin o Chronic smokers have low serum levels of 1-antitrypsin and elastase continues the unopposed destruction of elastic fibers present in the alveolar wall - Differs from asthma in that the abnormalities limiting airflow are irreversible and a destructive process targets the lung parenchyma Acute respiratory distress - Severe and sudden lung condition marked by widespread inflammation in the lungs, leading to difficulty breathing and low blood oxygen levels - Results from a disruption of the normal barrier that prevents leakage of fluid of alveolar capillaries into the interstitium and alveolar spaces - Two mechanisms can alter the alveolar barrier: o Increase in hydrostatic pressure in the alveolar capillaries - caused by failure of the left ventricle or stenosis of the mitral valve = increased fluid and proteins in the alveolar spaces o 2.Hydrostatic pressure is normal, but the endothelial lining of capillaries or the epithelial lining of alveoli is damaged - inhalation of agents such as smoke, water (near drowning), or bacterial endotoxins (resulting from sepsis), or trauma can cause a defect in permeability - 1st phase: Acute exudative process o Interstitial and alveolar edema o Neutrophil infiltration o Hemorrhage and deposits of fibrin  o Cellular debris deposit in the alveolar space and form hyaline membranes - 2nd phase: Proliferative o Alveolar cells proliferate and differentiate to restore the epithelial alveolar lining o Returning gas exchange to normal in most cases o In other cases, the interstitium displays inflammatory cells and fibroblasts = invasion of alveolar spaces through gaps of the basal lamina o Hyaline membranes are either removed by phagocytosis by macrophages or invaded by fibroblasts - 3rd phase: Chronic fibrosis o Occlusion of blood vessels and chronic fibrosis o Outcome depends on improvement of the systemic condition - Treatment is focused on neutralizing the disorder causing ARDS and providing support of gas exchange until the condition improves. Kidney stones - Hard deposits that form in the kidneys when minerals and salts in urine crystallize, causing severe pain and potential blockages in the urinary tract - Can form in the kidney and pass in the ureters - If they are large enough, they cause excessive distension of the ureteric wall - Develop when there is an imbalance in the substances that make up urine, leading to the formation of crystals that can aggregate and grow into stones within the kidney - Main causes: o Dehydration = concentrates minerals in the urine o Certain dietary factors, such as high intake of oxalate-rich foods or excessive salt o Family history of kidney stones o Medical conditions affecting the urinary tract - UTIs - Symptoms o Intense pain in the back or side (often referred to as renal colic) o Blood in urine o Frequent urge to urinate o Painful urination o Cloudy or foul-smelling urine - May pass on their own, but larger stones can cause blockages, leading to more severe symptoms and requiring medical intervention. Salpingitis - Inflammatory process of the oviduct - The most common pathology affecting the tubes and is usually part of a pelvic inflammatory disease affecting the uterus, the tubes and the ovaries - Usually results from a bacterial infection, leading to scarring of the tubes and subsequent tubal ectopic pregnancy Ectopic tubal pregnancy - Implantation of fertilised ovum in the mucosa of the uterine tubes - May occur due to obstruction of the uterine tubes by pus = pyosalpinx - Usually results in a tubal abortion, a rupture of the uterine tube, during the first 8 weeks of gestation - Can cause haemorrhage into the peritoneal cavity, which can spread into the rectouterine pouch or into the uterovesical pouch - This can lead to inflammation of the parietal peritoneum, with the resulting pain referred to the right lower quadrant of the abdomen. - Can be misdiagnosed as acute appendicitis, as it causes inflammation of the peritoneum in the same area Uterine prolapse - Uterus descends/falls into the vagina - Usually uterus is in the typical anteverted and anteflexed position directly on top of the bladder o Provides a support for the uterus when the abdominal pressure increases Retroflexion and Retroversion of the uterus - Retroflexion = condition where the uterus is tilted backward at the level of the cervix, with the body of the uterus angling toward the rectum rather than the usual forward position o Due to factors like childbirth, pelvic surgery, or conditions that affect pelvic ligaments - Retroversion = condition where the entire uterus is tilted backward, positioning the uterus with its fundus directed toward the spine o Caused by factors like congenital variations, pelvic adhesions, or weakening of supporting ligaments - Both conditions by asymptomatic or may experience pelvic pain, discomfort during intercourse, or menstrual irregularities Primary dysmenorrhea - Menstrual pain - Spasmodic and painful cramps in the lower abdomen that begin shortly before or at the onset of menses - In the absence of any pelvic pathology Secondary dysmenorrhea - Recurrent lower abdominal pain during or before menstruation that is due to an underlying condition - Possible causes o Endometriosis o Pelvic inflammatory disease o Intrauterine device o Uterine leiomyoma o Adenomyosis Endometriosis - Presence of endometrial tissue outside the uterine cavity - Believed to be due to a backward flow of tissue shedded during menses through the uterine tubes into the pelvis - Leads to scarring and connections of organs that should not be connected - Pelvic pain - Lower back pain - Dysuria Abnormal uterine/vaginal bleeding - Before the age of 9 - During pregnancy - After menopause Adenomyosis - Clinical condition where endometrial glands and tissue are found in the myometrium of the uterus - Can cause o Heavy or prolonged menstrual bleeding o Severe dysmenorrhea o Chronic pelvic pain o Painful intercourse Fibroids / uterine myomas / uterine leiomyomas / fibromas - Non-cancerous growths that develop in or around the uterus - Solid tumours made by smooth muscle cells and fibrous tissue - Can cause o Heavy or prolonged menstrual bleeding o Abnormal bleeding between menstrual periods o Severe pelvic pain o Low back pain o Painful intercourse Benign prostatic hyperplasia - Occurs with aging, is a non-cancerous enlargement of the prostate gland - Can restrict the flow of urine through the prostatic urethra - The periurethral mucosal (central zone) and submucosal (transition zone) prostate glands and cells of the stroma undergo nodular hyperplasia - Periurethral nodular hyperplasia produces: o Difficulty in urination and urinary obstruction caused by partial or complete compression of the prostatic urethra o Retention of urine in the bladder or inability to empty the urinary bladder completely = possibility of infection = inflammation of the urinary bladder and urinary tract infection - Attributed to DHT = metabolite of testosterone - Can metastasize to bones via blood vessels in 1/3 of men older than 75 Calcific aortic valve disease - A progressive disorder characterized by the gradual accumulation of calcium deposits on the aortic valve, leading to thickening, stiffness, and impaired valve function - Typically starts with the deposition of calcium on the aortic valve leaflets, causing them to become less flexible and more rigid over time - This process may lead to stenosis (narrowing) or regurgitation (leakage) of the aortic valve - Causes: o Aging o Hypertension o Smoking o Diabetes - Symptoms: o Initially asymptomatic in the early stages o As the disease progresses, symptoms may include chest pain or discomfort, shortness of breath, fatigue, and, in severe cases, heart palpitations or fainting