Week 5 Flashcards
Causes of hepatitis?
Viral (Hep A-E) Non-viral Drugs e.g. paracetamol Alcohol Poisons e.g. Aflatoxins Other e.g. pregnancy, circulatory insufficiency
What do hepatitis viruses A-E all have in common?
All are hepatotropic i.e. are able to infect hepatocytes (liver cells). However are all part of different virus families
6 stages of viral replication?
Adsorption Penetration Uncoating Replication of nucleic acid Maturation/ assembly Release
Hep A Virus: Viral features? Transmission? Shellfish as a source of infection? Stages of infection?
Viral features:
• Picornaviridae family
• Single-stranded RNA virus
• Non-enveloped virus (naked) • Only 1 serotype
Transmission:
– Faecal-oral route
– Poor hand hygiene
– Contaminated food or water
Shellfish as a source of infection:
If water is contaminated with sewage when shellfish filter water, the virus concentrations in flesh. Eating raw or partly cooked shellfish leads to infection
Stages of infection:
• Incubation period of 2-4 weeks leads into prodromal phase (a.k.a pre-icteric stage)
• Virus excreted in faeces for 1-2 weeks before symptoms
• Translocation from GI tract to blood
• Infection of liver cells
• Passage to biliary tract and back to GI tract
• Excretion in faeces
HAV:
Clinical features?
Treatment?
Prevention?
Clinical features: • Fever, anorexia • Nausea, vomiting • Jaundice • Dark urine, pale stools • No chronic carriage • Presence of anti-HAV IgM
Treatment?
• No specific treatment
• Maintain comfort and nutritional balance
• Fluid and electrolyte replacement
Prevention: • Vaccine • Good hygiene • Resistant to chlorination • Killed by boiling for 10 mins
Hep B Virus:
Viral features?
Antigens?
Viral features:
• Hepadnaviridae
• Double-stranded DNA virus
• Enveloped virus
Antigens:
- HBsAg= Surface antigen. Indicates high transmissibility and provide immunity
- HBcAg= Core antigen
- HBeAg= Envelope antigen. Indicates high infectivity
HBV:
Transmission?
Transmission:
• Sexual intercourse
• Intra-uterine, peri- and post-natal infection
• Blood or blood products
• Contaminated needles and equipment used by intravenous drug users
• In association with tattooing, body piercing and acupuncture
• Contaminated haemodialysis equipment
HBV: Stages of infection?
• Incubation period of 2-4 months
• 50% patients develop chronic active hepatitis
–> 20% of these proceed to cirrhosis
–> 1-4% of these risk developing liver cancer
HBV, difference between an acute and chronic infection?
- HBsAg and HBeAg appear during incubation period
- Viral DNA becomes detectable
- Antibodies to core antigen (HBcAg) appear concomitantly with rise in liver transaminases
- Antibodies to HBeAg and HBsAg only appear during convalescence
- Continued presence of HBsAg and absence of antibodies to it indicate that infection has become chronic
Chronic: No antibody for surface antigen. Surface antigen levels don’t drop down. Leads to infection
Stages of an acute HBV?
- Incubation period of 45 – 120 days
- Pre-icteric period of 1 – 7 days
- Icteric period of 1 – 2 months
- Convalescent period of 2 – 3 months in 80-90% of adult cases
Clinical features of icteric period of HBV? Cause?
Yellowish pigmentation: Skin, sclerae, other mucous membranes
Caused by hyperbilirubaemia
What does fulminant mean?
Severe and sudden in onset
Clinical outcomes of acute HBV infection?
• Fulminant hepatitis
• Chronic hepatitis or asymptomatic carrier
state
• Resolution of infection
HBV treatment and prevention?
Treatment:
• Pegylated interferon (peginterferon): superior
compared to α-interferon alone
• Nucleoside analogues such as oral lamivudine
Prevention: • Vaccination: 3 injections over 6 months. Against the surface antigen • HBV immunoglobulin • Blood screening • Needle exchange programmes • Sexual health education
Hep C Virus:
Viral features?
Clinical features?
Viral features: • 6 virus types (from nucleotide sequences) • Flaviviridae • Single-stranded RNA • Enveloped virus
Clinical features: • Usually asymptomatic • Fatigue • Nausea • Weight loss • May rarely progresses to cirrhosis • Small proportion of patients may develop hepatocellular carcinoma many years after primary infection
HCV:
Transmission?
Stages of infection?
Transmission: • Blood and blood products • Blood contaminated needles • Tattooing, body piercing, acupuncture • Haemodialysis
Stages of infection:
• Virus replicates mainly in hepatocytes
• Incubation period 2 weeks to 6 months
HCV: Prevention and treatment?
Prevention:
- Screening: Blood test based on NAAT
- No vaccine
Treatment:
- Ribavirin + pegylated alpha-interferon.
- Combination therapy(HAART) : Sofosbuvir, boceprevir, telaprivir, daclatasvir
HBV: Clinical Features of Pre-icteric Period?
- Malaise
- Anorexia
- Nausea
- Pain in right upper quadrant (tender liver)
Hep D Virus:
Viral features?
Viral features:
• Small (35nm) circular single-stranded RNA virus
• Defective virus
• HDV picks up HBsAg as it buds from liver cell (i.e. only comes in co infection with HBV)
HDV: What is function of HBV? Transmission? What increases risk for HDV infection? Treatment?
What is relevance of HBV:
• Found as co-infection with HBV
• HBV serves as helper virus for infectious HDV production
Transmission: Percutaneously, sexually, from infected blood
What increases risk for HDV infection: Chronic HBV carriers are at risk for infection with HDV
Treatment: None
Hep E Virus: Viral features? Incidence? Transmission and symptoms? Prevention?
Viral features:
• Caliciviridae
• Single-stranded RNA
• Non-enveloped virus
Incidence: Young adults. Can be life-threatening in pregnant woman
Transmission and symptoms: • Waterborne disease • Incubation period 3-8 weeks • Usually self-limiting • Signs and symptoms are similar to other acute forms of hepatitis
Prevention:
• Good sanitation & hygiene
• Vaccine (Hecolin)
6 other causes for viral hepatitis?
- Epstein-Barr virus
- Cytomegalovirus
- Yellow fever virus
- Adenoviruses
- Bunyaviruses
- Flaviviruses
- List the causes of release of erythropoietin by the kidneys.
High altitudes
Haemorrhage
Red blood cell destruction
Increased tissue oxygen demands
The ability of RBCs to carry O2 determines the release of erythropoietin
- List the functions of erythropoietin.
Sustains red blood cell production
Stimulates bone marrow cell that are committed to becoming red blood cells.
- Describe how chronic renal failure affects the release of erythropoietin and what the consequence of this is.
As chronic renal failure progresses, the scarring that occurs leads to a decrease in functioning cells and a drop in the release of erythropoietin.
As a consequence, there is a reduced capacity of the blood to carry oxygen and the patient may present with lethargy as a result of anaemia.
- Describe how low levels of erythropoietin are treated in chronic renal failure.
Synthetic erythropoietin is now used in therapy to counter these effects.
- List the main actions of calcitriol (1,25-dihydroxycholecalciferol).
- Stimulate the absorption of ingested Ca by increasing expression of Ca channels used to transport Ca across the cell membrane at the intestinal mucosa.
- Increases phosphate absorption
- Calcification of bone matrix by stimulation of osteoblasts and osteoclasts, facilitating the remodelling of bone
- Describe the effects of chronic renal failure on calcitriol production.
In renal failure, 25-hydroxycholecalciferol is not converted to 1,25-dihydroxycholecalciferol.
The kidneys add a hydroxyl group in this conversion
- Describe the effects of chronic renal failure on bone.
Leads to osteomalacia (softening of the bones) and osteoporosis (loss of bone tissue leading to brittle bones)
What structure becomes the posterior abdominal wall?
The mesoderm by lateral folding that enclose intra-embryonic coelom (The peritoneal cavity)
How does the mesoderm form the peritoneal cavity and posterior abdominal wall in development?
- The mesoderm forms somites adjacent to the notochord and developing neural tube.
- These form intermediate and lateral plate mesoderm
- The lateral plate mesoderm cavitates to form the coelom
- Folding moves the intermediate mesoderm to the posterior abdominal wall while the coelom becomes the peritoneal cavity
What are the two points from which urinary and reproductive systems begin development?
- Mesoderm and coelomic epithelium of the posterior abdominal wall
- Endodermally derived cloaca (divided by the urorectal septum) and the allantois
What does the renal primordia in the mesoderml form sequentially 3 times to form?
The renal primordia form sequentially 3 times within the mesoderm of the posterior abdominal and pelvic walls.
Forms the pronephros, mesonephros and metanephros.
Where do the mesonephric ducts open into?
The cloaca
The cloaca is being divided by the urorectal septum into:
Anteriorly: Urogenital sinus and allantois
Posterioly: Recto-anal region posteriorly
By the 5th week, what stages is the urogenital system in development?
The ureteric bud (on each side) extends from the mesonephric (Wolffian) duct and induces the metanephros that is forming in the pelvis.
The metanephros will become the definitive kidney
The metanephric blastema lie adjacent to each other
The ureteric bud gives rise to the _____ and ______ ducts
The metanephros becomes the renal tissue i.e. glomeruli and loops of _____
The kidney is functional by about __ weeks
If the collecting ducts do not meet the nephric vesicles, ____ form within the kidney
The ureteric bud gives rise to the ureter and collecting ducts
The metanephros becomes the renal tissue i.e. glomeruli and loops of Henle
The kidney is functional by about 10 weeks
If the collecting ducts do not meet the nephric vesicles, cysts form within the kidney
What 2 abnormalities can occur when the kidney ascend from the pelvis up the posterior abdominal wall?
- Pelvic kidney (1 risen, 1 in pelvic)
2. Horseshoe kidney (1 fused kidney in the pelvis
What is the consequence of abnormal branching of the ureteric bud before it reaches the metanephric blastema?
Bifid ureter
If the ureteric bud fail to branch at all within the metanephros, then there will be no induction of kidney development. Condition?
Renal agenesis
1 ureter may end up going to bladder, 1to vagina
Ureteric bud extends from the…
Mesonephritic (Wolffian) duct
The urogenital sinus will eventually form the..
Bladder and urethra
Relationship between the urogenital sinus and mesonephric ducts and ureteric buds?
The urogenital sinus (bladder and urethra) grows and the mesonephric ducts and ureteric buds (ureters) become incorporated within its walls
Ureteric buds eventually form the..
Ureters
Eventually what happens to the mesonephric ducts?
The mesonephric ducts move caudally to open in to the urethra as the vas deferens and ejaculatory ducts
From weeks 4-6 what 4 major changes to the urogenital system development occur?
- The cloacal membrane “sinks” into a pit of ectoderm as the underlying mesoderm proliferates
- The urorectal septum (mesoderm) completely separates the cloaca and becomes the perineal body
- The cloacal membrane ruptures leaving the anal canal and UG sinus open to the exterior
- The roof of the UG sinus is the urethral plate
The proximal part of the UG sinus ____ ____ _____, while the allantois closes to become the ______, which may remain patent
The pelvic part of the UG sinus becomes the prostatic and membranous ____
The distal part of the endodermal UG sinus or ______ UG sinus is drawn along the floor of the extending genital tubercle as the ______ ______
The proximal part of the UG sinus becomes the bladder, while the allantois closes to become the urachus, which may remain patent
The pelvic part of the UG sinus becomes the prostatic and membranous urethrae
The distal part of the endodermal UG sinus or definitive UG sinus is drawn along the floor of the extending genital tubercle as the urethral plate
Which 4 main embryological structures for the urinary system
The metanephros, ureteric bud, urogenital sinus and allantois
During week 6, the ___mesonephric duct develops lateral to the mesonephric duct as an invagination from a cord of coelomic _____l cells
The mesonephric and ____mesonephric ducts form the reproductive ducts and structures, while the ____ is formed in the mesoderm of the genital ridge, which is developed from the overlying coelomic epithelium; and ____ ____ that have migrated from the yolk sac endoderm
During week 6, the paramesonephric duct develops lateral to the mesonephric duct as an invagination from a cord of coelomic epithelial cells
The mesonephric and paramesonephric ducts form the reproductive ducts and structures, while the gonad is formed in the mesoderm of the genital ridge, which is developed from the overlying coelomic epithelium; and germ cells that have migrated from the yolk sac endoderm
Which cells become the cells that produce ova and sperm
Germ cells
How does female and male genital development begin to differentiate?
Males from mesonephric
Females from paramesonephric
Absence of the Y chromosome and the SRY gene leads to female development from the paramesonephric ducts, while the mesonephric ducts degenerate (due to lack of testosterone)
At week 8!
Mesonephric remnants found near vagina and ovary?
Mesonephric remnants: Gartner’s cysts near vagina or epoophoron and paroophoron near ovary
In male genital development, the appendix epididymis is a remnant of the proximal end of?
The mesonephric duct
Whilst paramesonephric ducts degenerate but remain as the appendix testis and the prostatic utricle
Female genital development:
The two __________ (Mullerian) ducts meet in the midline and fuse with each other and with the sino-____ ___ that is derived from the posterior aspect of the urogenital sinus
During months 3 to 5, the ducts zip together in a cranial direction to form the proximal vagina and the ____
Further cranially, the ducts stay separate as the ___ and ____ uterine tubes, with fimbriated ends that are open to the coelomic (peritoneal) cavity
As the ducts lift off the posterior abdominal wall they lift peritoneum as the ____ _______
The uterus and vagina may be septate and even double.
The two paramesonephric (Mullerian) ducts meet in the midline and fuse with each other and with the sino-vaginal bulb that is derived from the posterior aspect of the urogenital sinus
During months 3 to 5, the ducts zip together in a cranial direction to form the proximal vagina and the uterus
Further cranially, the ducts stay separate as the left and right uterine tubes, with fimbriated ends that are open to the coelomic (peritoneal) cavity
As the ducts lift off the posterior abdominal wall they lift peritoneum as the broad ligament
The uterus and vagina may be septate and even double.
6 uterine abnormalities during development
- Double uterus + double vagina (due to incorrect fusion of paramesonephric fusion)
- Double uterus
- Bicornate uterus
- Separated uterus
- Unicornate uterus
- Cervical atresia
As the gonads become more differentiated from the surrounding mesoderm, they remain “tethered”, cranially and caudally by what?
The suspensory ligament and the gubernaculum that extends to the labioscrotal folds
How do the testis migrate from the abdominal wall to the scrum?
Name a congenital condition that results in incomplete descent?
The gubernaculum shrinks to draw the testis down the posterior abdominal wall to the inguinal canal, then through the canal during the 8th and 9th months, so the testis should be in the scrotum by birth
Cryptorchidism: Failure of complete descent
What is the process in vaginalis?
If it stays open?
The loop of parietal peritoneum that the testis takes into the scrum.
If it stays open = Indirect inguinal hernia, hydrocele will form
The urogenital sinus gives rise to an endodermal urethral plate (between the adjacent ectodermal plates or ridges raised by underlying mesoderm) to form the _______ _____.
In males = growing into the penis, penile ______ and scrotum
In females= Remaining as the _____, and the separate labia minora and majora
The urogenital sinus gives rise to an endodermal urethral plate (between the adjacent ectodermal plates or ridges raised by underlying mesoderm) to form the external genitalia.
In males = growing into the penis, penile urethra and scrotum
In females= Remaining as the clitoris, and the separate labia minora and majora
In the male, during week 6 the urethral folds that form on either side of the urethral _____, fuse with the genital tubercle to grow with it, and create the urethral ______ between
The folds and groove stop short of the end of the ______ ______ (glans penis), but the urethral plate continues distally as a solid cord of (endodermal) cells
In the male, during week 6 the urethral folds that form on either side of the urethral plate, fuse with the genital tubercle to grow with it, and create the urethral groove between
The folds and groove stop short of the end of the genital tubercle (glans penis), but the urethral plate continues distally as a solid cord of (endodermal) cells
As the penis elongates, the edges of the urethral folds move towards each other and fuse in the midline to create the penile ______
The ______ “zips-up” from proximal to distal
The solid cellular cord in the glans ______, joins the penile urethra, and also forms the external ____
-As the penis elongates, the edges of the urethral folds move towards each other and fuse in the midline to create the penile urethra
The urethra “zips-up” from proximal to distal
The solid cellular cord in the glans ______, joins the penile urethra, and also forms the external _____
Male genetalia congenital abnormalities:
- Glans hypospadias?
- Penile hydrospadias?
Abnormal canalisation of the urethra in the glans causes glans hypospadias
Failure of the urethral folds to form, or to extend along the penis and fuse throughout its full length causes penile hypospadias
What feature of the urogenital system and anal canal predisposes them to fistulae formation?
Their common origin
6 functions of the renal system?
- Regulation of ECF volume and bp
- Regulation of osmolarity
- Maintenance of ion balance
- Regulation of pH
- Excretion of waste
- Production of hormones
Kidney structure
Outer cortex (contains superficial glomeruli 90% and the remaining glomeruli are Juxtamedullary) Inner medulla (divided into renal medulla pyramids with interlobular arteries/veins inbetween). Pyramid contain duct of Bellini that drain into the renal pelvis --> ureter
5 stages that occur in the nephron from glomerulus to collecting duct
- Filtration by glomerulus
- Obligatory absorption (most of water and ions) and secretion (toxins etc) by proximal tubule
- Generation of osmotic gradient by loop of Henle
- Regulated absorption and secretion by distal tubule
- Regulation of water uptake by collecting ducts
Structures present within the glomerulus?
Bowman’s space with the capillary tuft with fenestrated walls sitting within it
