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201
7
Phase 1 Revision Session
Grace Mussell & William Martin
26.03.17
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Topics
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Intro
Cells
Homeostasis Acid Base Balance
DNA/RNA Histology Exam stress
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Introduction
• IMMS is a large module
• Make sure you look over:
• CELLS, HOMEOSTASIS, MOLECULAR BUILDING BLOCKS, DNA/RNA, MITOSIS/MEIOSIS, GENETIC DISEASES, METABOLIS, ATP, FATTY ACID OXIDATION/ KETONES, ACID/BASE/BUFFER, OXYGEN TOXICITY AND HISTOLOGY……
• The following slides are a selection of some of the key points…
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Cells
NUCLEUS -­‐ Contains DNA
-­‐ Double nuclear membrane -­‐ Produces rRNA for protein synthesis MITROCHONDRIA
-­‐ Has ring of DNA (from mum)
-­‐ Site of oxidative phosphorylation, Krebs (matrix)
-­‐ Energy house The Peer Teaching Society is not liable for false or misleading information…
Cells
RER AND SER -­‐ Rough = protein synthesis -­‐ Smooth – membrane lipid production, protein processing, detoxify drugs GOLGI APP
-­‐ Process and modify ER products (different jobs in different places)
VESCILES/LYSOSOMES/PEROXISOMES
-­‐ Storage, transportation and exchange
-­‐ Waste CYTOSKELTON -­‐ Filament proteins supporting structure of the cell
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Cells
Phospholipid bilayer: • Barrier the external environment and compartmentalise the cell
• Semi-­‐permeable:
▪ absorb nutrients and expel waste
▪ maintain intracellular ionic balance
▪ Cell response to signals
• Molecules for intercellular adhesion
• Fluid mosaic structures • Lipophilic drugs can go straight through to reach metabolising enzyme The Peer Teaching Society is not liable for false or misleading information…
Cells
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Cells -­‐ Endocytosis
Energetic process to absorb/engulf
molecules into cell.
Phagocytosis
(eating) -­‐ macromolecules/ entire cell to form phagosomes
Pinocytosis
(drinking) -­‐ dissolved solutes
Receptor mediated -­‐ specific, depressed areas: coated pits.
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Cells -­‐ Exocytosis
Vesicles from the Golgi complex
Fuse with the plasma membrane
Expulsion of waste or secretion of enzymes/hormones The Peer Teaching Society is not liable for false or misleading information…
Cells – Movement of substances
▪ Passive diffusion
▪ Gaseous exchange along chemical gradient
▪ Facilitated diffusion through protein channels with(out) carrier proteins
▪ Glucose transport – protein channel upregulated by insulin. ▪ Voltage gated channels -­‐ activated by action potentials.
▪ Active transport
▪ NaK ATPase pump -­‐ going against chemical and electrical gradients
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Homeostasis
= Control of the internal environment
Homeostasis is the property of a system in which variables are regulated so that internal conditions remain stable and relatively constant
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Homeostasis
Positive feedback -­‐ amplification of signal
§ Clotting cascade
§ Oxytocin during childbirth
Negative feedback = centre of homeostasis § Blood sugar regulation
§ Blood pressure regulation
§ Metabolism/thyroid regulation
§ Temperature regulation
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Homeostasis -­‐ Communication
Types
▪ Endocrine -­‐ hormones
▪ Nervous -­‐ currents and neurotransmitters
▪ Immune -­‐ antibodies, cytokines, interleukins
Receptors + ligands The Peer Teaching Society is not liable for false or misleading information…
Homeostasis
Immunity
-­ T lymphocytes secreting IL2, cytokines
Neuro synapses, neuromuscular junction, clotting
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Endocrine system -­ hypothalamus, pituitary, thyroid, parathyroid, thymus, pancreas, kidney, gonads, adrenals
Homeostasis -­‐ Hormones
Peptide • Proteins or short chain AA
• Some glycoproteins (carbohydrate side chains)
• Act FAST
• Large, hydrophilic charged molecules that cannot diffuse across a membrane. • Extracellular receptor (on membrane)
EXAMPLES
Insulin, growth hormone, TSH & ADH The Peer Teaching Society is not liable for false or misleading information…
Homeostasis – Types of hormone Steroid • Synthesised from cholesterol
• Lipid soluble -­‐ cross membranes but require transport proteins
• Intracellular receptor • SLOW EXAMPLES
Testosterone, oestrogen & cortisol Amino-­‐acid derivative -­‐ adrenaline, T4, T3
● synthesised from tyrosine
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Homeostasis – Water Distribution THIS WILL BE ON THE EXAM! WHAT PERCENTAGE OF THE BODY WEIGHT IS WATER? 60%
HOW MANY OF LITRES OF WATER IS IN THE AVERAGE BODY?
42L
HOW MANY LITRES OF THIS IS INTRACELLULAR?
28L (40% OF BODY WEIGHT)
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Homeostasis – Water Distribution HOW MANY LITRES OF THIS IS EXTRACELLULAR?
14L (20% OF BODY WEIGHT)
14 + 28 = 42L
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Homeostasis – Water Distribution WHAT 3 THINGS MAKE UP THE EXTRACELLULAR FLUID?
-­‐ INTERSTITIAL – surround cells -­‐ PLASMA – Circulates as extraceullar component of blood
-­‐ TRANCELLULAR – CSF, digestive juices and mucus
HOW MUCH FLUID MAKES UP INTERSTITIAL 10L
HOW MUCH FLUID MAKES UP PLASMA
3L
HOW MUCH FLUID MAKES UP TRANSCELLULAR 1L 10+3+1 = 14
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Homeostasis – Water Distribution The Peer Teaching Society is not liable for false or misleading information…
Homeostasis – Water Distribution WHAT SYSTEM IS REALLY IMPORTANT IN WATER HOMEOSTASIS? RAAS
WHAT SIGN DO YOU GET WHEN YOU GET LOTS OF EXTRACELLULAR FLUID? OEDEMA
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Homeostasis – Oedema
Oedema -­ excess water in the intercellular tissue space.
● inflammatory (leakage)
● Venous (increased end pressure)
● Lymphatic (blocked)
● Hypoalbuminaemic
Serous effusion -­ excess water in a body cavity
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Homeostasis – Definitions Osmosis -­ net movement of solvent molecules through a semipermeable membrane to a higher solute concentration.
Osmolality -­ measure of the number of the osmoles (Osm) of solute per kilogram of solvent (osmol/kg or Osm/kg),
Osmolarity -­ defined as the number of osmoles of solute per liter (L) of solution (osmol/L or Osm/L).
Osmotic pressure -­ pressure applied to a solution, by a pure solvent, required to prevent inward osmosis. Through a semipermeable membrane.
Oncotic pressure -­ form of osmotic pressure exerted by proteins that tends to pull fluid into its solution
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Homeostasis – Water Homeostasis Water loss from ECF
● ↑ solute or ↓ fluid results in an ↑ osmolality
● Detected by osmoreceptors in hypothalamus
● Release of antidiuretic hormone (ADH) from posterior pituitary
● ADH acts by increasing water reabsorption in the kidneys
● Dilutes solute and returns ECF water to normal
Decreased renal blood flow
● ↓ water in ECF results in ↓ circulating volume results in ↓ renal blood flow
● Kidney release of Renin and activation of RAAS
● Angiotensin II and aldosterone increase Na+ reabsorption (exchange K+ and H+) bringing water. Also stimulates ADH.
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Homeostasis – Water
Dehydration
Excess
Low intake/excess loss/ low ADH High intake/decreased loss/ excess ADH ▪ Water deprivation
▪ Vomiting
§ Hyponatraemia
▪ Diarrhoea
§ Cerebral over-­perfusion
▪ Burns
o headache
▪ Heavy Sweating
o confusion
▪ Diabetes insipidus
o convulsions
▪ Diabetes mellitus
▪ Drugs
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Homeostasis – Electrolytes
WHAT IS THE MOST COMMON INTRACELLULAR ELECTROLYTE? POTASSIUM WHAT IS THE MOST COMMON EXTRACEULLAR ELECTROLYTE?
SODIUM, CHOLRIDE AND BICARBONATE
WHAT ELSE WOULD YOU FIND EXTRACELLULAR? UREA, GLUCOSE
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Homeostasis – Sodium Hypernatraemia = high sodium Causes: renal failure, mineralocorticoid excess & osmotic diuresis Consequences: cerebral intracellular dehydration Hyponatraemia = low sodium Causes: diuresis, Addison's disease, IV fluids & oedema Consequences: Intracellular over hydration, hypotension The Peer Teaching Society is not liable for false or misleading information…
Homeostasis – Potassium Hypokalaemia
= low potassium Causes: D&V, diuretics, alkalosis, hypomagnesaemia Consequences: weakness & dysrhythmia Hyperkalaemia
= high potassium
Causes: renal failure, diuretic/ACE inhibitors, Addison’s, Acidosis Consequences: risk of MI Excretion from the kidneys is controlled by aldosterone as it controls the Na/K pump
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Homeostasis – Calcium Hypercalcamia = High calcium -­ “painful bones, renal stones, abdominal groans, and psychic moans”
Causes: hyperparathyroidism, malignancy, VD toxicity & TB Consequences: metastatic calcification, stones Hypocalcaemia = low calcium Causes: Vit D deficiency, Mg deficiency, renal disease, parathyroidectomy, intestinal malabsorption Consequences: tetany (spasms of the hands, feet and voice box) The Peer Teaching Society is not liable for false or misleading information…
Acid Base Balance -­‐ Defs
• Acid:
– Proton/H+ donor
– HA ⇔ H+ + A-­‐
• Base:
– Proton/H+ acceptor
– B + H+ ⇔ BH+
• Buffer:
– Solution which resists changes in pH when small quantities of strong acids or base are added
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Acid Base Balance
pH of body fluid is maintained by...
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Acid Base Balance
●LUNGS
& intracellular
or extracellular buffers
●KIDNEYS
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Acid Base Balance
•
•
•
•
•
Ideal pH: 7.4
Normal pH range: 7.35-­‐7.45
pH >7.45 – alkalosis
pH <7.35 – acidosis
Can be respiratory or metabolic
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Acid Base Balance -­‐ Henderson-­‐
Hasselbalch equation pH = pKa + log ([HCO3 -­‐ ] / [CO2])
pH = 6.1 + log ([HCO3-­‐]/[H2CO3])
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Acid Base Balance -­‐ Henderson-­‐
Hasselbalch equation ●Blood pH should be 7.4 ●Therefore ratio below MUST
equal 1.3
Acid Base Balance -­‐ Henderson-­‐
Hasselbalch equation As soon as this fraction ≠ 1.3 ...
ACIDOSIS or ALKALOSIS
Acid Base Balance
Lungs/Respiratory:
• Acidosis: hyperventilate and blow off CO2
• Alkalosis: slow down, retain CO2
• Rapid response, limited effect
Kidneys/Metabolic:
• Acidosis: excrete H+, retain HCO3-­‐
• Alkalosis: retain H+, excrete HCO3-­‐
• Delayed response, greater effect The Peer Teaching Society is not liable for false or misleading information…
Acid Base Balance
Other point to note...
● LUNGS can compensate for acidosis/alkalosis immediately
● Kidneys take 1-­‐2 days to reach maximal functioning ● So kidneys cannot compensate in severe asthma attack but will compensate in long term conditions-­‐ eg. emphysema
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DNA/RNA What unwinds the double helix?
Topoisomerase What then separates the DNA apart thereby exposing the nucleotides? Helicase What enzyme creates new strands of DNA?
DNA polymerase
Reads 3’ to 5’ – creates DNA by working in pairs to make 2 new strands of DNA
Starts at a primer Primer = short strand of DNA that is the start point for DNA synthesis as DNA polymerases can only add nucleotides onto an existing strand of DNA.
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DNA/RNA The Peer Teaching Society is not liable for false or misleading information…
DNA/RNA DNA REPLICATION
• Semi-­‐conservative DNA replication (one parent strand + one new strand)
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DNA/RNA -­‐ Production of proteins Transcription
-­‐ Needed for gene expression –
proteins bring about the actions of genes
-­‐ Double stranded DNA à single stranded RNA -­‐ RNA polymerase reads the DNA and produces an antiparallel RNA
Promoter à stop codon Promoter = A specific sequence that RNA polymerase binds to – initiation of transcription Stop codon = Stops transcription, creating a RNA transcript The Peer Teaching Society is not liable for false or misleading information…
DNA/RNA -­‐ Production of proteins Splicing
Pre-­‐mRNA = introns + exons Pre-­‐mRNA à splicing à mature mRNA Different combinations of exons allow for many different proteins to be made The Peer Teaching Society is not liable for false or misleading information…
DNA/RNA -­‐ Production of proteins Translation
-­‐ Ribosome
-­‐ mRNA sequence is used as a template to bind to complementary tRNA molecules at anticodon. -­‐ tRNA molecules are attached to specific aa. -­‐ Linked by peptide bond = a protein The Peer Teaching Society is not liable for false or misleading information…
DNA/RNA -­‐ Mis-­‐sense/non-­‐sense Mis-­‐sense mutation A point mutation in which a single nucleotide change results in a codon that codes for a different amino acid (substitution)
Varied effect – silent mutation à non functional protein Examples: Sickle-­‐cell disease CAG à CTG Non-­‐sense mutation Point mutation that produces a stop codon – results in an incomplete, usually non-­‐functional protein Examples: Duchenne’s muscular dystrophy The Peer Teaching Society is not liable for false or misleading information…
DNA/RNA -­‐ Exam practise
A tumour cell in the synthesis phase of the cell cycle begins the process of DNA replication.
Which of the below splits the two DNA strands apart?
A. Adenosine
B. Cysteine
C. DNA polymerase
D. Helicase
E. Topoisomerase
Answer: D – Helicase
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DNA/RNA -­‐ Exam practise
While analysing human genetic material, a geneticist observes that sample A contains single stranded nucleic acids and sample B is composed of double stranded nucleic acids. Which of the below bases will be found only in sample A and not in sample B?
A. Adenine
B. Cytosine
C. Guanine
D. Thymine
E. Uracil
Answer: E – Uracil
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DNA/RNA -­‐ Exam practise
A forensic scientist is presented with a minute quantity of cellular material from a crime scene. The sample contains only a few cells. In order to produce a sample that is large enough for analysis, he adds the components of DNA to the sample. Which other substance must be added to catalyse the amplification of the sample?
A. DNA polymerase
B. Guanine
C. Thymine
D. Topoisomerase
E. Uracil
Answer: A – DNA polymerase
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Histology
• Boring, but essential – don’t neglect
• Don’t solely rely on the pictures that circulate –
they did use different ones last year • Think pattern cognition and things that are clinical • Appears across all 3 papers • Function dictates form
• Only covered epithelium but look at what cells look like
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Histology -­‐ Epithelia
• What name is given to the lining surrounding tissues of the body or body cavities?
– Epithelia • List some functions of epithelia – Shield underlying tissues from mechanical or chemical damage
– Exchange/secretion of substances The Peer Teaching Society is not liable for false or misleading information…
Histology
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Histology
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Histology
WHEN IS SQUAMOUS EPITHELIUM REPLACED WITH COLUMNAR CELLS? The Peer Teaching Society is not liable for false or misleading information…
Histology
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Histology -­‐ Staining
Alcian Blue
• Polysaccharides
• GAGs
• Cartilage
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Histology -­‐ Staining
Eosin
• Red blood cells
• Cytoplasmic proteins
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Histology -­‐ Staining
Haematoxylin
• Nuclei
• RNA
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Histology -­‐ Staining
PAS
• Polysaccharides
• Glycoproteins
• Glycolipids
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Histology -­‐ Exam practise
A woman is experiencing pain in her chest which can be described as “heart burn”. She goes to the endoscopy clinic to get a biopsy taken. They take samples from her GI tract and upper airway.What is the epithelium of the oesophagus? (3 marks)
Non keratinising stratified squamous epithelium
A sample found is made up of simple columnar, non-­‐ciliated epithelium. Where is this sample likely to be taken from? (2 marks)
Stomach, small and large bowel, rectum (various other areas too)
The epithelium of the skin is simple squamous keratinising. Name 3 roles of a keratinising squamous epithelium (6 marks)
Withstanding shearing forces/abrasion, keeping hydrated and protected from dehydration by glycolipids, keeping infection out
Name 3 types of cell junction (3 marks) Adhesion, tight, gap, desmosome, hemidesmosome
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Exam stress -­‐ Breadth of knowledge as opposed to depth
-­‐ If everyone doesn’t understand it, just leave it
-­‐ Think clinically – if you look it up Wikipedia and there isn’t a clinical section to it, then don’t bother.
-­‐ Public health – don’t neglect this!
-­‐ Statistics – don’t over worry yourself – it will come up but get marks elsewhere. The Peer Teaching Society is not liable for false or misleading information…