1
Q
Describe the structure of a molecule of DNA.
A
Is a polymer
Deoxyribose sugars are joined together by a phosphodiester linkage from carbon 5 on one sugar to carbon 3 on the other
The phosphate backbone is on the outside of the DNA double helix with the sugar inside & the base on the inside
2
Q
How does base pairing work?
A
the 2 complementary strands of DNA anneal or hybridise together. The DNA double strand is held together by H bonds formed between the base pairs across the 2 different strands
- adenine forms 2 hydrogen bond with thymine
- guanine forms 3 hydrogen bonds with cytosine
3
Q
What is the overall charge of DNA? How does this come about?
A
Overall negative charge due to phosphate groups being on the outside (which are negatively charged)
4
Q
When/how are chromosomes (i) condensed (ii) spread out?
A
(i) As cells divide in metaphase, makes them more easily visible
(ii) During interphase, they are spread & dispersed. Although they are often still clustered near their own chromosomes (shown by staining)
5
Q
How is DNA packaged? How many turns (and in what direction) does DNA make around a single histone?
A
In multiple layers
The 1st involved 147 bases associated with an octomeric histone core (protein) to form a unit called a nucleosome
1.7 left handed turns around a single histone
6
Q
Describe the structure of histones, what is special about histone H1?
A
Histones (H2A, H2B, H3 & H4) are positively charged & have a long N-terminus. This tail protrudes from the nucleosome
Histone H1 has 2 termini (N&C) & sits inside the point at which DNA is coming off the “bead”
7
Q
Describe how chromatin is formed.
A
The 1st stage of coilign creates a 10nm fibre which is then coiled again with the help of histone H1 to create a 30nm fibre. Yet more condensing creates a 300nm supercoiled structure.
During metaphase, and more condensing, a 700nm structure is made (a typical chromatid)
8
Q
How can chromatin be decondensed? What are the 3 ways in which histones can be modified & what does this, in turn, affect?
A
Using ATP, they are decondensed by a remodelling complex to allow protein access
Histones can be modified post translationally by acetylation, methylation & phosphorylation.
This affects the degree to which the associated genes are transcribed
9
Q
What are the 2 types of DNA repeats? Describe them both.
A
INTERSPERSED repeats: SINE & LINE often derived from retroviruses (21% of human genome)
TANDEM repeats: unlike the above, these are adjacent repeats including:
- satellites: telomere TTAGGG
- minisatellites: 7-100 bases repeated ever 40000 bases
- microsatellites: 1-6 bases repeated >500 bases
10
Q
When is repetitive DNA used? Describe a condition for which it is used.
A
Can be used in forensics to compare a sample DNA to a number of known samples to find a match
- MYOTONIC DYSTROPHY involves a trinucleotide repeat (microsatellite) that is unstable when transmitted through mitosis
11
Q
Describe mitochondrial DNA.
A
circular DNA that is maternally inherited
SIDENOTE: it is through mtDNA that we have discovered the ‘out of Africa’ theory
12
Q
What are the 6 factors which ensures the skin as a defensive barrier? Describe them.
A
- EPIDERMIS - stratum corneum (hard horny layer of dead cells) forms a lipid bilayer
- Very DRY surface
- ACIDIC pH 5.5
- SWEAT secretion produces an increase in salt concentration and greater osmotic pressure
- ANTIMICROBIAL substances e.g. fatty acids, sebum, defensins are produced by resident microbial flora
- sebum contains lysozyme, capable of destroying bacterial cell wall - RICH BLOOD & LYMPHATIC SUPPLY ensures rapid specific and non-specific immune responses
13
Q
What are the 6 ways that pathogens can enter the body?
A
- Keratinised epithelium (e.g. ringworm)
- Epidermis (e.g. impetigo)
- Hair follicles (e.g. folliculitis)
- Subcutaneous fat (e.g. cellulitis)
- Fascia (e.g. necrotising fasciitis)
- Muscle (e.g. gas gangrene)
14
Q
What are the 3 routes of infection? Give examples for each.
A
- SKIN: pores, hair follicles
- WOUNDS: scratches, cuts, burns
- BITES: insects, animals
15
Q
What are the 4 types of bacterial infection of the skin?
A
- Staphylococcus aureus
- Streptococcus pyogenes
- Pseudomonas aeruginosa
- Myobacterium tuberculosis
16
Q
Describe (i) Streptococcus pyogenes (ii) Staphylococcus aureus (iii) pseudomonas aeruginosa.
A
(i) Cocci morphology, grown in chains, gram positive, group A streptococcus, multiple virulence factors, beta-haemolytic
(ii) Cocci, grown in clusters, gram positive, causes a huge range of illnesses, multiple virulence factors, direct infection, or effect, of toxin
(iii) coccibaccilus, gram negative, opportunistic pathogen, colonises catheters etc, produces exotoxin A
17
Q
What are the 4 types of skin lesions? Describe each of them.
A
- Macule = flat, red, local inflammation
- Papule = raised, red, more marked inflammation
- Vesicle = small blister
- Ulcer = disruption of epithelium
18
Q
Give an example of a fungal infection, describe it. What are certain predisposing conditions of candida albicans?
A
CANDIDA ALBICANS
- a type of yeast commensal
- however it can lead to candidiasis
Predisposing conditions include Ab treatments, corticosteroid treatment, cytotoxic therapy and diabetes mellitus
19
Q
What are the 5 types of viral infection? What do they result in?
A
- Human papilloma virus - warts
- Herpes simplex virus 1 - cold sores
- Human simplex virus 2 - genital warts
- Varicella zoster virus - chicken pox or shingles
- Coxsackie A virus - hand, foot and mouth disease
20
Q
Give an example of a parasite of the skin. What is causes and how this occurs.
A
Scarcoptes scabei (mite)
- the mite burrows into the skin with the female laying eggs
- infection is asymptomatic
- hypersensitivity to eggs/their surface proteins may occur
- scratching of the skin may lead to superinfection with streptococcus pyogenes
21
Q
Describe the concept of semi-conservative replication of DNA.
A
DNA strands are anti-parallel
- one strand has a free hydroxy group on the 5’ carbon at one end & a free hydroxy on the 3’ carbon on the opposite end. This is base paired to another strand in the opposite direction.
- the strands are copied via the semi conservative model in which each strand of the original DNA is replicated such that the daughter molecule consists of one old strand (template) & one newly synthesised strand
22
Q
Why is it DNA replication is initiated at many sites? How is this done?
A
Each eukaryotic chromosome is one linear DNA double helix averaging 10^8 base pairs long. With a replication rate of 2kb/minute, replicating one human chromosome would require 35 days. As a solution, DNA replication initiates at many different sites simultaneously - this occurs by forming replication forks
23
Q
How is DNA replicated? From the use of the Okazaki fragment to the use of DNA polymerase to complete the lagging of the strand.
A
Replication is asymmertrical & DNA in short fragments, discontinuously, called okazaki fragments. For DNA to be synthesised in Okazaki fragments an RNA primer is required. A new RNA primer is synthesised by RNA primase
- DNA polymerase ADDS to the new RNA primer to start the okazaki fragment. DNA polymerase finishes the DNA fragment & the old RNA primer is erased & replaced by DNA
- The ‘nick’ between Okazaki’s is sealed by DNA ligase joining them to the growing chain. The exposed single stranded DNA at the replication fork is protected by single-strand DNA binding protein due to the unstable nature of single strands of DNA, the binding protein must be removed to re-expose the DNA=> replication can occur
- at end of new lagging strand is a repetitive telomere sequence. Telomerase binds to the exposed strand of DNA, it has a bound RNA template which can bind with homology to end of DNA fragment. This allows telomerase to add additional repeats to the template strand. The DNA polymerase completes the lagging of the strand
24
Q
How often do polymerases make mistakes? What is done DURING replication to correct them?
A
Polymerases make mistakes as often as once every 10,000 polymerisation events. This can lead to mutations if not corrected before the next round of replication.
- errors are removed during synthesis by DNA polymerase. It has two ‘pockets’; an active site where polymerising occurs & as this is complete it twists the template so that as the template passes out of the enzyme, it binds to the editing site
- if the base pair is found to be wrong it is removed & replaced with the correct base pair.
25
How are mutations repaired post-replicatively? How many errors is there for x number of genomes (approximately)?
By mismatch repair or as defects predispose to disease
| - there's approximately 1 error for every 3 genomes replicated
26
Describe the technique of PCR (polymerase chain reaction).
The region of DNA to be amplified is heated up to separate the strands by disrupting H bonds. The solution is allowed to cool & primers that are complementary to the single stranded DN are added. There's a primer to go in each direction for each anti-parallel strand
- DNA polymerase & individual nucleotides are added to allow DNA synthesis from the primers. This process is repeated to produce lots of copies from a small strand
27
What 3 things is PCR used for?
1. Detect the presence of an infectious agent
2. Detect inheritance patterns
3. Look for changes in the number of copies of a chromosome
28
What is DNA sequencing? How is it done?
Single stranded DNA is added along with primers, DNA polymerase & nucleotides
- there's a large proportion of normal precursors & a small amount of dideoxyribonucleoside triphosphate molecules
- the rare incorpporation of the terminal nucleotides by DNA polymerase blocks further growth of the DNA molecule
- the different lengths of strands are separated by electrophoresis to determine the DNA sequence
29
When is PCR & DNA sequencing used clinically?
Blood sample can be taken from an infected person. Cells removed by centrifugation and the viral RNA genome can be extracted
- reverse transcriptase/PCR amplification is undertaken, this then can be compared to the blood of a non-infected person by electrophoresis
30
What is the function of the kidneys? (HINT: there are 3 main functions)
1. They maintain homeostasis by the production of urine, which is the removal, from the circulating blood, of excess water & electrolytes, and toxic, metabolic waste products such as urea & creatinine
2. Also monitor the acid/base balance by excreting H ions during ACIDOSIS, or bicarbonate ions during ALKALOSIS
3. They secrete renin which increase BP & erythropoetin which accelerate RBC production
31
Where, within the body, are the kidneys located?
One on each side, on the posterior abdominal wall, high up, under the diaphragm.
- They are retroperitoneal, encapsulated & protected by layers of fascia and fairly firm renal fat
32
How many times is blood filtered & cleaned each day?
Up to 60 times
33
Describe and explain the structure of kidneys, ensuring to mention renal pyramid, calyces, hilum & the ureter.
Has a cortex & medulla, with the renal pyramids (housing the nephrons with their function of filtration & reabsorption) projecting into the calyces of the collecting system
- minor calyces converge on major calyces, which themselves form the renal pelvis at the hilum
- the pelvis becomes the ureter that transports the urine to the bladder
34
What is the blood supply of the kidneys?
Supplied by the renal arteries which arise directly from the aorta at L2 & enter the hilum along with the renal veins (going to the inf vena cava) & renal pelvis
NOTE: the L renal artery is SHORTER than the R renal artery and vice versa with the veins as the inferior vena cava lies to the RIGHT of the aorta
35
What are the kidneys susceptible to?
To trauma and infection
| - their ducts may become obstructed by stones (calculi) & congenital abnormalities are NOT uncommon
36
What is a nephron? What 5 important features does it consist of?
```
The functional unit within the kidney, housed within the renal pyramids
Consists of:
1) Renal corpuscle (glomerulus)
2) Proximal convoluted tube (PCT)
3) Loop of Henle
4) Distal convoluted tube (DCT)
5) Collecting duct
```
37
What is the function of the ureter? Where is it located? Where does it pass in (i) males (ii) females?
Conducts urine to the bladder, where it's stored
Is RETROPERITONEAL, on the posterior abdominal wall, from here it must reach the bladder (which is anterior)
(i) passes between the vas deferens & seminal vesicle
(ii) is posterior to the ovary & inferior to the uterine artery, passing the cervix & vagina
38
What is the function of the urinary bladder? What is the lining of the bladder formed of? What type of epithelium is it made from AND why is this epithelium used?
Peristaltic waves propel urine DOWN the ureter and the bladder fills by relaxation of its muscular wall - the detrusor muscle
- the muscle is smooth and involuntary, however, the external sphincter around the urethra is striated and under voluntary control
- the epithelial lining is transitional epithelium OR urothelium, which is urine proof & allows for distension
39
Where within the body is the bladder located?
Rests on the levator ani by puberty
| Located anteriorly behind the pubic bone in the midline
40
What nerves is the detrusor muscle supplied by?
Parasympathetic nerves derived from S2,3,4
41
What 4 surfaces does the bladder have? How do the ureters pass into the bladder and WHY.
A postero-superior surface, 2 infero-lateral surfaces and a base.
The ureters pass into the bladder OBLIQUELY to prevent reflux
42
The bladder neck leads to the urethral opening, what is the difference in males & females at this point?
MALES have a preprostatic, internal sphincter (sympathetic) to prevent semen backflow
FEMALES the bladder neck is above the pelvic floor and so the pressure of the pelvic organs and levator ani contribute to urinary continence
43
When the bladder distends what happens to the peritoneum? Where does the bladder now lie? What does this allow for? What happens to the ileum and sigmoid colon?
It pushes the peritoneum upwards, above & behind itself
- when this occurs the bladder now lies directly behind the anterior abdominal wall & so a catheter may be placed urethrally OR suprapubically
- in BOTH sexes the ileum & sigmoid colon drop into the pelvis, on their mesenteries, and lie over the bladder
44
What is the blood supply of the bladder? What is the lymphatic supply of the bladder?
Primarily supplied by the internal iliac artery, the superior vesicle artery and the inferior vesicle artery
- venous drainage is via a plexus on the infero-lateral surfaces to the internal iliac veins
LYMPH DRAINAGE of the bladder is to the external iliac nodes
45
What is the function of the urethra? Describe the structure in (i) males and (ii) females.
For the passage of urine OUT of the body
(i) described in four parts, with an internal & external sphincter at the 1st and 3rd part respectively
1) Pre-prostatic part
2) Prostatic part
3) Membranous part (deep perineal pouch)
4) Spongy part
(ii) the urethra is shorter & passes through the deep perineal pouch. It only has an external sphincter
46
What is micturation? The bladder can hold 400ml of urine, what happens if this reaches 500ml?
Urination
| Pain in the lower abdomen and perineum
47
What does the word HEALTH mean?
A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity
48
What is PUBLIC HEALTH?
The art and science of preventing disease, promoting health and prolonging life through the organised efforts of society
49
What are the 3 domains of public health practice?
Health promotion
Improving services
Improving health
50
What were the first 4 waves of public health?
1. Great public works, municipalism
2. Refinement of scientific approach - germ theory of disease, hospitals, health visitors
3. Restructing of institutions - welfare reforms, new housing, social security, NHS
4. Focus on risk theory of disease, lifestyle issues - smoking, diet and physical activity
51
What are the 8 fundamental conditions and resources for health?
1. Peace
2. Shelter
3. Education
4. Food
5. Income
6. Stable ecosystem
7. Sustainable resources
8. Social justice & equity
52
Give 5 examples of the marmot principles.
Give every child the best start in life.
Enable all children, young people and adults to maximise their capabilities and have control over their lives.
Create fair work and good employment for all.
Ensure health standard of living for all.
Create and develop healthy and sustainable places and communities.
Strengthen the role and impact of ill-health prevention.
53
What are the 5 different forms of RNA? What are their function?
1. mRNA: genetic message
2. tRNA: adaptor
3. Xist: structural
4. snRNA: spliceosome
5. rRNA: ribosome
54
What is an (i) intron (ii) exon?
(i) region of DNA which does NOT code for proteins
| (ii) region of RNA which codes for proteins
55
What is the use of DNA in trnascription?
Used as a template, complementary to one strand
56
Describe RNA polymerase (compared to DNA polymerase). Why is RNA polymerase not as accurate? What is mRNA identical to?
RNA polymerase is not as fast as DNA polymerase
- it does NOT require a primer to start
It is not as accurate as DNA replication as DNA polymerase has 2 active sites
The mRNA is identical to the non-coding strand, multiple copies of mRNA are made simultaneously
57
How do RNA polymerases know when to START and STOP?
The promoter region initiates transcription of a particular gene. It is located near the transcription start sites of genes, on the SAME strand and upstream on the DNA.
The terminator region indicates transcription to STOP, when RNA polymerase reaches the terminator region it lets go of the DNA and STOPS building the strand of mRNA
58
Different RNA polymerases generate different RNAs, list the first 3.
RNA poly 1 - rRNA
RNA pol 2 - protein coding RNA
RNA pol 3 - tRNA
59
What is the promoter of RNA polymerase 2? Describe the location and function of said promoter.
TATA sequence/box.
| - found 25 bases before the start site of the sequence that generates protein coding RNA
60
What is TBP? What is its function?
TATAbox binding protein
- it identifies the TATA sequence.
The promoter is a binding site for TBP which distorts DNA once bound making it easier for RNA polymerase to work on
61
What is a transcription factor? Why are these transcription factors needed?
A protein that's able to identify a particular sequence in DNA and communicate to RNA polymerase.
The binding of TBP is NOT enough to stimulate the binding of RNA polymerase and so therefore transcription factors are needed
62
What are the general principles of RNA transcription?
Trans-acting factors bind to cis-acting promoter and RNA polymerase binds to this complex
RNA polymerase II is UNABLE to bind directly to promoter, therefore transcription factors bind to cis-elements at promoter. RNA poly II is recruited and transcription begins
63
What is a housekeeping gene?
Encoding proteins that are required in ALL cells ALL the time. It has a promoter that is GC base rich and requires different families of transcription factors
64
Transcription factors have 2 domains, what are these 2 domains?
1) DNA binding domain
| 2) Activation domain
65
What is mRNA processing? How is it done?
Before mRNA is used to make proteins it's processed
- initially the RNA is capped. A methyl group is added to the 5' end of the transcript - added that the polymerase has moved about 25 bases downstream (as it's physically blocking the mRNA)
66
What happens when RNA falls off and STOPS polymerising? Why does this happen?
- another complex comes along and adds lots of adenine residues to the end of the message in a poly-A-tail
WHY: it helps to protect the exonucleases and marks the RNA ready for export
67
What is splicing used for? How is this done?
The introns from pre mRNA must be removed by RNA splicing to produce mRNA which is now useful.
- this is then exported OUT of the nucleus
This takes place through 2 esterification reactions via lasso shaped intermediate called a lariat structure
(1) Sequences embedded in the intron which generates an attachment to the splice donor site creating a branch to create lasso structure.
(2) The hydroxide group of exon can now attach to the other exon
68
What is splicing controlled by?
A complex called a spliceosome
- it contains small nuclear RNA (snRNA)
- the snRNA is not for messaging but has catalytic properties for the process of splicing
69
What is alternative splicing?
As a consequence of splicing we can create variants of proteins coming from the SAME, because our pre mRNA can be spliced in alternative ways
- some exons can be skipped to produce a different arrangement of exons on the FINAL mRNA
70
What is the number of different proteins made from the same gene called?
Gene Number Paradox
71
What is Frasier Syndrome?
A defect where the glomerulus has formed abnormally leading to problems in the kidney.
72
What is the purpose of (i) obturator internus (ii) levator ani?
(i) lines the pelvic lateral wall
| (ii) forms the muscular pelvic floor
73
What is the perineum? Where is it located?
The region BELOW the pelvic floor, it contains the genitalia and urethra
It is divided into superficial compartments by the perineal membrane
74
Where do the bladder and prostate rest?
The pelvic side walls form a hammock for the pelvic viscera
| The bladder & prostate rest on the levator ani (ie pelvic floor)
75
What are the testis and epididymis? What are they composed of?
are essentially packed with seminiferous tubules that create sperm, but testosterone is produced by Leydig cells in the interstices
- each testes is surrounded by the tunica vaginalis and suspended in the scrotum to keep cool. Sperm then passes from the tubules to the epididymis
The skin of the scrotum is rigose and contains dartose (smooth) muscle. It has a midline raphe and is divided by a septum
76
What is the blood, lymph and nerve supply of the testis and epididymis?
BLOOD: the testicular artery (arises from aorta at L2). The testicular vein starts as a pampiniform plexus which coalesces to form the vein (the left drains to the L renal vein whilst the right drains to the inf vena cava)
LYMPH is to para-aortic nodes
NERVE is sympathetic nerves from T10/11 (periumbilical)
77
What is the function of the vas deferens?
Carries sperm from the testis and epididymis to the urethra
- it passes through the inguinal canal, it emerges into the abdomen lateral to the inferior epigastric artery adn then lies on the lateral wall of the pelvis BEFORE joining the seminal vesicle to form the ejaculatory duct
78
What is the blood supply of the prostate and urethra in both males and females?
MALES: inferior vesicle artery, internal pudental artery and dorsal penile
FEMALES: urethra is supplied by vaginal artery and inferior vesicle artery
VENOUD DRAINAGE is via plexuses converging on the internal pudendal and internal iliac veins
79
What is the location and function of the seminal vesicles?
The left and right lie just ABOVE the prostate gland, sandwiched between the bladder and the rectum
- they secrete a seminal fluid to nourish sperm
80
What 2 types of things does the ovary produce? Where is it located? Whats its blood and nerve supply?
(1) ovum monthly in response to FSH and LH from the pituitary gland
(2) oestrogen and progesterone to maintain the uterine cycle
It hangs off of the posterior aspect of the broad ligament on a mesovarium (intraperitoneal)
- it is supported by the ovarian and suspensory ligaments
SUPPLIED: by the ovarian artery (arise from aorta at L1/2) and by sympathetic nerves derived from T10/11 (peri umbilical)
81
What is the uterine tube? What are the parts of the uterine tube? Where is it located? What is the blood supply?
Ostium surrounded by fimbrae -> infidubulum -> ampulla (where fertilisation occurs) -> isthmus and lastly to the intramural part through the uterine wall
Lie in the upper, free edge of the broad ligament and its blood supply from an anastomosis between the ovarian and uterine arteries
82
What is the function of the uterus? What are the 3 parts of the uterus? What is the purpose of the (i) broad and round ligaments (ii) cervix? Where is it located?
Pear-shaped central pelvic organ for implantation of the fertilised ovum and growth of the foetus
Has a fundus, body, cervix
(i) hold the uterus anteverted and anteflexed OVER the bladder (ii) pushes into the vagina, forming the fornices
The uterus tilts forward over the bladder. Coils of ileum and sigmoid colon lie on its upper surface and the rectum is posterior with the recto-uterine pouch between
83
What is the difference between the walls of the uterus and vagina? What is their blood supply?
Uterus has a thick muscular wall and a relatively narrow cavity
- the vagina has a distensible wall for intercourse and childbirth
BLOOD SUPPLY - by anastomosing uterine and vaginal arteries
84
Describe the difference between the 2 crura stuck to the perineal membrane in males and females?
In males they extend to form the corpura cavernose which fills with blood during arousal to produce ana erection
There's also corpus spongiosum, which starts at the bulb of the penis, housing the urethra to PREVENT compression during erection
85
What is the female breast? What is it composed of and where is it located?
Mammary gland for milk production
Glandular tissue in fibro-fatty stroma, 16 or so ducts that converge on the nipple
Lies opposite ribs 2-6, BUT has a tail extending into the axilla
86
What is the blood supply and lymph drainage of the female breast? What is the function of the suspensory ligaments?
BLOOD: essentially from axillary and internal thoracic arteries
LYMPH drainage is to the axillary and internal thoracic nodes
Suspensory ligaments pass from the underlying deep fascia to support the breast (BUT if involved in tumour may cause in-drawing of the skin)
87
What are the 3 levels of severity for tumours within the breast lymph drainage?
LEVEL 1 - anterior pec group
LEVEL 2 - central group
LEVEL 3 - apical group
MD2001
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