What are the 2 forms of defence? Describe them.
1. INNATE = the first line of defence. NOT improved on further exposure 2. ADAPTIVE = second line of defence. Improved on further exposure
What physical & biochemical barriers does the innate defence include?
1. PHYSICAL: barriers such as skin & epithelia, movement by cilia & trapping by mucus 2. BIOCHEMICAL: low pH such as sweat, vaginal secretions & stomach; lysozyme in secretions damage the cell walls of bacteria
If barriers are breached, what does the innate defence do?
It attempts to contain & localise the breach by sending phagocytic cells to DESTROY microbes
What chemicals are involved in the innate response? Describe them. (HINT: there's 4)
1. ACUTE PHASE PROTEINS: (secreted by the liver) e.g. CRP is an indicator of inflammatory response. It binds to certain phospholipids when cells are damaged to aid opsonisation 2. COMPLEMENT PROTEINS: increase permeability of vessels & start opsonisation e.g. C3b 3. INTERFERONS: limit viral replication in cells. They are proteins that are released in response to the entry of a virus. that have the property of inhibiting viral replication. IFN alpha & beta are released by most cells of the body, whereas gamma is only produced by T lymphocytes 4. CYTOKINES
What is an (i) antigen (ii) antibody?
(i) a toxin or other foreign substance that indices an immune response in the body (ii) a blood protein produced in response to, & counteracting, a pecific antigen. Haas 2 specific binding sites called Fab & a stem Fc that binds to receptors OR triggers complement which goes on to lyse, act as a chemotactic agent & as an opsonin
Describe (i) chemotaxis (ii) opsonisation.
(i) chemical signal to attract phagocytes. Is enhanced by complement proteins (ii) process of coating cell/bacteria with an opsonin. An opsonin is a substance that coats cell/bacteria & enhances the ability of phagocytes to phagocytose a particle
Define the various failures of the immune response? Giving examples also
Can occur through hypersensitivity, immunodeficiency, autoimmunity. The latter is when the immune system reacts to its self, with a loss of tolerance e.g. type 1 diabetes mellitus, rheumatoid arthritis
Relate immunology to development in the womb of the foetus.
The foetus gains IgG from the other which increases in concentration until birth. At this point, the newborn starts to quickly synthesise his/her own IgG IgM & IgA begin to creep up in numbers, just before & after birth respectively Oestrogen stimulates IgG & IgA production & secretion in the mother, oestrogen inhibits T cells which could reject the foetus
List the structures of the gastrointestinal tract.
1. Oral cavity (mandible, maxilla, lips, cheeks, tongue, floor of mouth, palate, fauces, tonsils) 2. Pharynx, oesophagus & stomach 3. Peritoneum & mesenteries 4. Small Intestine (Duodenum, jejunum, ileum) 5. Large intestine (Caecum with appendix, ascending, transverse, descending & sigmoid colon) 6. Rectum & Anal Canal 7. Liver & Biliary system 8. Pancreas
What are the boundaries of the oral cavity?
Maxilla Teeth Mandible (with body & ramus)
Describe the temporomandibular joint, what movement of this joint is made to OPEN the mouth?
TMJ is divided into 2 cavities by a disc The mouth is opened by protrusion & depression
Describe (i) Cheek & lips (ii) Floor of the mouth (iii) Hard Palate (iv) Soft Palate
(i) muscles of facial expression; buccinator, orbicularis oris, lip & angle elevators & depressors. They keep food in the mouth & between the teeth, speech formation. (ii) muscular 'diaphragm' suspended between the mandible & hyoid bone. It forms a mobile support for the tongue (iii) assists in bolus formation & separation from the nasal cavity (iv) hangs like a curtain at the back of the mouth to STOP food falling into the pharyns & larynx whilst chewing; tenses & elevates to separate naso from oropharynx during swallowing
Describe the tongue, mentioning its function, the main muscle for movement, its epithelium, the papillae & lymph drainage.
Is a bag of muscle for manipulating food & forming speech. Genioglossus is the main muscle (extrinsic) for movement of the tongue. There's also intrinsic (shape) & extrinsic (position) muscles) Epithelium = stratified squamous Superior part of the tongue is made furry by papillae, forms & then pushes bolus backwards to be swallowed Drains lymph to the submandibular lymph nodes & inferior deep cervical nodes. Drainage from the tongue crosses the midline, increasing the significance of lung cancer.
What is the function of (i) the palatoglossal arches (ii) tonsils ?
(i) separate the oral cavity from the oropharynx & the tonsils lie BEHIND them (ii) Clusters of lymphocytes around an invagination of overlying epithelium
What is the function of the salivary glands? List the 3 types & their supply.
Commence digestion, lubricate food & maintain healthy teeth & gums - parotid, submandibular, sublingual - receive a parasympathetic, secretomotory supply
What is the course of air & food through the pharynx?
Pharynx connects the oral cavity to the oesophagus. Food AND fluid must pass from the oropharynx to laryngopharynx to the oesophagus, NOT to the nasopharynx (hence elevation of soft palate) NOR to the airway (hence elevation & closure of larynx) - there's 3 constrictors to squeeze bolus towards the oesophagus, elevators to LIFT pharynx to receive bolus; whilst simultaneously laryngeal elevation for closure & airway protection during swallowing
Describe the functional anatomy of the oesophagus.
contains a physiological cardiac sphincter to PREVENT gastric reflux located in the posterior mediastinum (ie behind heart) Lower oesophagus = site of porto systemic anastomosis & portal hypertension, may cause oesophageal varices
What is the relation of the gut to the peritoneum?
Intra & retro peritoneal structures The mesentery = the neurovascular supply
Describe the blood supply of the GI tract.
Supplied by 3 branches that are anterior branches of the aorta: - coeliac trunk to FOREGUT (lower oesophagus, stomach, duodenum) - sup. mesenteric to MIDGUT (duodenum to 2/3 transv colon) - inf. mesenteric to HINDGUT (final 1/3 of transv colon to prox anal canal)
What is referred pain? Describe referred pain within the GI tract.
Autonomic nerves run with 3 arteries &, as our brain cannot localise visceral pain, the localisation instead occurs at the overlying parietal peitoneum: - coeliac trunk: refer to UPPER ABDOMEN - sup. mesenteric: refer to PERI UMBILLICAL region - inf. mesenteric: refer to SUPRAPUBIC region
Describe the anatomy & the blood supply of the stomach.
Is a distensible sac which holds food whilst it is being digested Pylorus = muscular sphincteric ring that opens under parasympathetic control to allow the chyme to pass into the duodenum The stomach is completely lined by simple columnar mucus secreting epithelium, there's also gastric glands that produce acid & digestive enzymes - Supplied by an anastomotic ring of BVs derived from the coeliac trunk, which also supplies the liver & spleen
What is the function of fibroblasts?
Synthesise collagen, elastin & proteoglycans
Describe (i) collagen (ii) elastin (iii) proteoglycans.
(i) synthesised in RER. Assembled to form a triple helix which is released via the secretory pathway (ii) found in BVs (like the aorta) which allows it to stretch & recoil. The surface of elastin is hydrophobic which causes it to "want" to recoil (iii) assemblages of glycosaminoglycans & proteins. They provide matrix support, cushioning & hydration. They are highly -vely charged and therefore binds alot of H2O. Links proteins of ECM & cell surface
Describe (i) glycosaminoglycans (GAGs) (ii) integrins
(i) LONG chains of repeating disaccharide units which are highly -vely charged due to the sulphate group which makes it highly hydrated (ii) links from collagen fibres & proteoglycans to the cell surface membrane
What are myofibroblasts? What is their function.
They secrete collagen - are smooth muscle like - involved in tissue repair of damaged tissue - they proliferate & secrete collagen, consolidate the damaged area & contract - they differentiate from fibroblasts under mechanical stress & are especially important in wound healing
What are the 3 functions of adipocytes?
insulation - subcutaneous packing - e.g. eye energy store
Describe the function of tight junctions. (HINT: there's 3 functions)
They define the polarity Control the passage of substance between cells Can link actin cytoskeleton
Describe the function and structure of adherens junctions.
Are cell adhesion spots/bands
The plaque anchors actin filaments at the membrane
Are NOT as dense as desmosomes
Distinct cadherins provide cell adhesion in different tissues, these can be extended molecules & are flexible
Link from cadherins via catenin to actin
Describe the structure & function of desmosomes.
Are links between strong intermediate filaments in adjacent cells. Cadherins are non-classical types.
Cytoplasmic dense plaque containing desmoplakin & plakoglolbin proteins, and keratin filaments are anchored to these cytoplasmic dense plaques
What is the structure & function of gap junctions?
Allow communication between cells
Hydrophillic channel which allows small molecules to pass to coordinate function
What is the cause of Duchenne Muscular Dystrophy?
Gene mutation causing the absence of dystrophin. Premature termination of translation
Damage to muscle fibre due to muscle tearing:
- muscle wasting
- muscle weakness
- unable to walk by 12 years
(SIDENOTE: in healthy individuals, dystrophin usually binds to actin)
Describe the spread of cancer in terms of cell adhesion.
1. Tumour cells accumulate, cells not breached BM, carcinoma in situ
- expression of cadherins reduced. Cells converted to 'mesenchymal' cells
- microinvasion starts aided by secretion of metalloproteases
- BM breached
- invading tumours overexpress integrins which promote cell proliferation/interaction with non epithelial cells during movement
3. PROGRESSION TO METASTASIS
- autocrine motility factors from tumour cells
- entry into blood & lymphatics
- dissemination to metastasis
There are 3 types of cell adhesion molecules; focal adhesions, hemidesmasomes & integrins. Describe each of them respectively.
1. FOCAL ADHESIONS link the ECM to cytoskeleton (actin filaments) through transmembrane proteins (integrins)
- Dynamic (e.g. in fibroblasts)
- also act as signalling platforms
- link to fibronectin
2. HEMIDESMASOMES linkn ECM to cytoskeleton (intermediate filaments) through transmembrane proteins (integrins)
- more stable (e.g. linking epithelial cells to BM)
- link to laminin in BM
3. INTEGRINS are a large family of proteins that bridges between the cytosol & ECM
What attempt was made to correct Duchenne Muscular Dystrophy?
PTC124 (Ataluren) - an experimental drug that was thought to override premature stop single mutation to produce normal dystrophin
List the 4 points of Koch's Postulates.
- The bacteria must be present in every case of the disease
- Bacteria must be isolated from the host with the disease & grown in pure culture
- The specific disease must be reproduced when a pure culture of the bacteria is inoculated into a healthy susceptible host
- The bacteria must be recoverable from the experimentally infected host
What 4 things does the innate immune system consist of?
What is the function fo normal flora in our body? What is it suppressed by?
Protects us by competing with pathogens for colonisation sites & producing antibiotic substances that suppress competing organisms
- it may produce toxic metabolic products to INHIBIT other microorganisms & they may alter pH
Is suppressed by antibiotics
What are the 4 types of physical barriers of the innate immune system?
1. SKIN - secretes sebum & fatty acids to inhibit growth, although some microbes have evolved mechanisms to penetrate it
2. MUCOMUCILIARY CLEARANCE - particles settle on sticky mucus of respiratory epithelium & debris is transported by cilia to the oropharynx, where it is swallowed
3. FLUSHING - urinary tract
4. PERISTALSIS - gastrointestinal tract
What are the 4 chemical barriers of the innate immune system?
- antimicrobial products - lysozyme, lactoferrin, defensins
- gastric acid (pH 2 or 3)
- plasma proteins - complement, CRP, mannose-binding lectin, transferrin
What are the 5 types of phagocytic cells?
- dendritic cells
- mast cells
When does an infection occur? In what 2 ways can this occur?
Occurs when a microorganism causes ill-health
This occurs in 2 ways:
- invading host tissue
- by exerting effects from mucosal surfaces
Define (i) commensal (ii) pathogen (iii) pathogenicity (iv) virulence.
(i) microorganism which forms part of the normal microflora
(ii) microorganism capable of causing an infection
(iii) capacity to cause disease
(iv) meaure of the capacity to cause disease
What are the 3 types of pathogen? Describe them respectively.
1. OBLIGATE PATHOGEN = almost always associated with disease (e.g. HIV)
2. CONDITIONAL PATHOGEN = may cause disease if certain conditions are met (e.g. s.aureus)
3. OPPORTUNISTIC PATHOGEN = usually only infects an immunocomprimised host
What are the 4 ways that infection can be established?
- microbes with specific mechanisms for attachment & penetration of host's body surfaces
- microbes introduced into host by biting arthropods
- microbed introduced into host by skin wounds OR animal bites
- microbes able to infect ONLY when host defences are impaired
What is tissue tropism? What does it define? What are the influencing factors? What are the virulence factors?
The affinity for a specific tissue
- defines the cells & tissues of a host that support the growth of a particular microbe
- some microbes have a broad tissue tropism, others may infect a single tissue
Influencing factors = presence of cell receptors, transcription factors, local temperature, physical barriers, pH e.g. HIV. hep B, varicella zoster virus
Virulence factors = toxic secretion, antibiotic resistance, pilus formation, capsule, iron transport systems, adhesion factors & enzymes
What are the steps of infection?
Attachment & entry
Evasion of host defences
How does antibiotic resistance occur?
From resistant genes on plasmids producing enzymes that degrade the anitbiotic e.g. MRSA, VRSA
What 3 factors does transmission depend upon?
- number of microorganisms shed
- microorganisms stability in environment
- number of microorganisms recquired to infect a fresh host
What are the 4 types of transmission?
- Human-to-human (respiratory, faeco-oral, urinary)
- Animal-to-human (zoonoses)
- Fomite transmission (inanimate objects)
- Nosocomial infections (acquired during hospital stay)
What are the 4 differences bewteen endotoxins and exotoxins?
- low toxicity
- part of cell wall of gram -ve
- low specificity
- high toxicity
- produced from both gram +ve and gram -ve
- secreted from bacterial cells
- can be converted into toxoids for vaccine use (cholera toxin)
What are the 5 stages of a group's "life"?
- Forming - orientation to task and group, identifies boundaries
- Storming - Conflict and polarisation. Team members challenge and question
- Norming - cohesiveness, acceptance & understanding. Focus on task
- Performing - performance of task, flexible roles & function
- Adjourning- task ends, sense of loss
What are the individual roles adopted by members of a group?
TASK ROLES: initiator, coordinator, information seeker, information giver, energiser
MAINTENANCE: the encourager, the comprimiser, the group observer & commentator, the follower
DYSFUNCTIONAL ROLES: agressor, blocker, recognition seeker, dominator
Describe the duodenum, including its location, function & any special features.
It is RETROPERITONEAL & forms a C-shaped curve around the pancreas
It is split into 4 parts (superior, descending, inferior, ascending) of which the descending receives the combined bile & pancreatic ducts at the Ampulla of Vater
FUNCTION = neutralise gastric acid BUT continue digestion, especially of fats & commences absorption
- the wall is folded & villous to create huge absorptive surface
Describe the jejunum & ileum, their location, function & any other special features.
Are suspended on mesenteries & continue absorption (which is aided by the adddition of a HUGE amount of fluid to chyme)
- the ileum enters the 1st part of the colon - the caecum - in the right iliac fossa
What is the function of the colon, what are the parts of the colon? Mention the splenic & hepatic flexure.
Absorbs fluid to dry out the chyme & create faeces
Ascending & descending parts are RETROPERITONEAL
Transverse & sigmoid parts are on a mesentery
- the ascending becomes transverse at the hepatic flexure, and the transverse becomes descending at the splenic flexure
Where is the appendix located? What is it derived from? Where does early appendicitis refer pain to?
Hangs from the caecum on a short mesentery
Derived from a branch of the superior mesenteric artery & carries nerves derived from spinal cord segments T10/11
Early appendicitis refers pain to the peri-umbilical region, which later moves to the right inguinal region where the parietal peritoneum is involved.
What is the (i) function (ii) location of the rectum?
(i) stores faeces prior to defecation
(ii) is ABOVE the pelvic floor (levator ani) & leads to the anal canal
What is the epithelium in the anal canal? What is the pectinate line?
Pectinate line is the division between the rectum & anal canal, here the nerve supply changes & it is v.sensitive to pain BELOW the line
What is the muscle in the (i) internal anal sphincter (ii) external anal sphincter?
Where is the liver located? What is the blood supply?
It is the largest organ in the body
Lies across the upper abdomen, under the diaphragm, surrounded by peritoneum, except for the bare area posteriorly
Supplied by the hepatic portal vein, bringing nutrients from the stomach & gut, & the hepatic artery which supplies the hepatocytes with oxygen. Venous drainage is by hepatic veins that enter the inferior vena cava.
What is the function of the liver? What is the porta hepatis?
The liver produces bile which is drained via canaliculi, which lie between the hepatocytes, into the bile ductules & eventually into bile ducts
Also responsible for the storage of glucose & glycogen, the detoxification of metabolic waste & the synthesis of blood clotting factors
The portal vein, hepatic artery & heaptic ducts enter the liver at the porta hepatis
What is the function of the falciform ligament? Where is the quadrate lobe located & where is the caudate lobe located?
Separates the L & R lobes
Quadrate lobe is next to the gall bladder
Its visceral surface shows the caudate lobe next to the inferior vena cava
What are the constituents of bile? What are bile pigments derived from? What is the role of bile salts?
Constituents = bilirubin, cholesterol, phospholipids, fatty acids, water & electrolytes
Bile pigments are derived as breakdown products of haemoglobin. Kupffer cells (fixed phagocytes) play a role in their formation
Bile salts are responsible for the detergent & emulsifying effects of bile on fats, they also increase absorption fats by the small intestine
What is the function of the gall bladder? What are the 3 parts of a gall bladder?
Stores (60ml) & concentrates bile (non essential functions)
Has a fundus, body, neck
Drains bile to the cystic duct which combines with the hepatic duct to form the bile duct & enter the 2nd part of the duodenum with the pancreatic duct at the Ampulla of vater
What is the location of the pancreas? What is its function? What is its blood supply?
Is RETROPERITONEAL (except tail) & lies close to major BVs making it difficult to access
Has BOTH exocrine & endocrine function: the former is to secrete digestive proenzymes to the pancreatic duct (which joins the bile duct)
Blood supply is mainly via the splenic artery (from the coeliac trunk) as well as the pancreato-duodenal arteries (from sup mesenteric artery or coeliac trunk)
From superficial to deep, the skin is made up from the epidermis, dermis & hypodermis, describe each of the layers.
EPIDERMIS is epithelial tissue derived from the ectoderm
DERMIS is a connective tissue derived from the mesoderm
HYPODERMIS is also derived from the mesoderm, but unlike the dermis it's NOT derived from the dermatome region of the mesoderm
What structures are continuous with & in development formed from the epidermis?
Sweat glands, hair follicles, along with their sebaceous gland
Describe the junction between the epidermis and dermis.
Is very uneven
There is ridges and grooves on the deep surface of the epidermis have a COMPLEMENTARY pattern to the underlying dermis (which is the dermal papillae)
What does the (i) papillary layer of dermis (ii) deeper reticular layer composed of?
(i) fine, loosely arranged bundles of collagen fibres
(ii) thicker bundles of collagen fibres arranged in a NETWORK
What type of epithelium is the epidermis? What cells does it contain? (name them & describe) (HINT: there's 4 cell types)
Stratified Squamous Keratinised
KERATINOCYTES - cells which undergo keratinisation
MERKEL CELLS - tactile corpuscles that aggregate and form touch receptors
MELANOCYTES - derived from neural crest cells, produce melanin to protect against UV radiation
LANGERHANS CELLS - derived from bone marrow, are antigen presenting cells
Thick skin is composed of 5 layers, name and describe these layers from superficial to deep.
- Stratum CORNEUM - horny layer with dead keratinocytes to PREVENT water loss & entry of antigens
- Stratum LUCIDUM - translucent layer of approx 6 layers of keratinised cells
- Stratum GRANULOSUM - granular layer of approx 6 layers
- Stratum SPINOSUM - prickle/spiny cell layer of variable thickness
- Stratum BASALE - single layer continually producing keratinocytes
What layer does thin skin NOT contain?
What is desquamation? How long does it take?
The process of dead cells falling off
Takes 15-30 days depending on WHICH body part you're looking at
Describe the structure of a sweat gland.
Consists of a coiled part in the deep and underlying dermis (where sweat is made)
And a straight duct that passes through the dermis and epidermis to open onto either skin OR a hair follicle
What are the 2 types of sweat gland? Describe them both.
1. ECCRINE - simple coiled tubular sweat gland that secretes a watery fluid. Lies in the dermis and superficial fascia. The duct opens onto the SURFACE of the skin. Controlled by the symathetic NS important in thermoregulation and a response to fear
2. APOCRINE - found in axillae and genital region. Open into the hair follicles and release a milky secretion containing pheromones
What is a pilosebaceous unit composed of? Decribe each of its sub-units. (HINT: there's 3)
1. HAIR FOLLICLE - cylindrical, epithelial structure anchored in hypodermis. The hair shatf grows from the bulb and the shaft is composed of keratin
2. SEBACEOUS GLAND - produces and secretes sebum to lubricate the hair and adjacent skin
3. ARRECTOR PILI MUSCLE - smooth muscle, attached to the papillary dermis and to the sheath of the follicle. Makes hair stand up for WARMTH (SNS)
Describe the 5 types of sensation & what sense organs are associated with each.
- PAIN: nocioceptors fire when tissues are being damaged OR are close to being damaged (free nerve endings)
- TEMPERATURE: separate receptors for cold & heat (F.N.E)
- TOUCH: Meissner's corpuscles (in papillae of dermis and detect touch and vibrations) or Merkel cells (dome shaped, detect fine touch). Just beneath epidermis
- PRESSURE: Pacinian corpuscles (deeper than meissner, detect pressure and vibration). In dermis
- VIBRATION: Meissner's and Pacinian corpuscles. Dermis
What is sub lethal injury? Give an an example.
Due to a hydropic change when the cel balloons with water & sodium (ONCOSIS) making certain processes less efficient
e.g. A fatty change such as too much alcohol in the liver, depleting NADPH from the metabolism pathway
They do vary in the nature of the injury e.g. acute vs chronic, mild vs severe, what cell type is affected
What is lethal injury and when does lethal injury occur? What are the 6 types of necrosis? Describe them
When the integrity of the cell membrane is lost. Is known as necrosis, it induces inflammation and repair
- it is normally whole tissues destroyed NOT just one cell
- COAGULATIVE - most common, coagulation of cellular proteins. Initially firm and later soft
- COLLIQUITIVE - in brain. Dead cells are liquefied
- CASEOUS - in Tb, pale yellow semi-solid material (cheese like)
- GANGRENOUS - with putrefaction. Wet form (from bugs) and dry form (ischaemia)
- FIBRINOID - associated with malignant hypertension
- FAT - may follow trauma and cause a mass OR may follow pancreatitis visible as multiple white spots
What is apoptosis? What is the difference between PCD and apoptosis?
APOPTOSIS - involves shrinkage of the cell without losing membrane integrity. The cell then splits into various vesicles each containing different organelles. They are phagocytosed by neighbouring cells. No inflammation present
Apoptosis is MORPHOLOGICAL, PCD is INTENT
Tissues can be grouped into one of three categories depending on HOW they divide and thus whether or not they can regenerate. Name and describe these three categories.
- LABILE (e.g. epithelial cells, blood, gut) - are dividing/proliferating ALL the time and so can generally be regenerated. E.g. psoriasis (cells should take 28 days but only 3-4 days in psoriasis to proliferate)
- STABILE (e.g. hepatocytes, fibroblasts and endothelial cells) - can proliferate in response to damage. E.g. damage to liver - hepatocytes tiggered via complex signals to divide
- PERMANENT (e.g. neurones, cardiac and skeletal muscle) - CANNOT regenerate
What are the 3 things that can happen after injury?
Describe (i) healing (ii) repair.
(i) resolution with no, or minimal, residual effect. E.g. superficial skin abrasion, incised wound healing via 1st intention)
(ii) the next best option when there is tissue loss. E.g. healing via 2nd intention
When is healing via 1st intention used? What is the process?
A skin incision where little tissue has been lost
The apposed edges of the incisioin are joined by a thin layer of fibrin, which is ultimately replaced by collagen which is covered by surface epidermis
By the end of the 1st month the scar tissue consists of cellular connective tissue and tensile strength now increases
When is healing via 2nd intention used? What is the process involved?
Wound with separated edges as MORE tissue lost
Becomes filled with granulation tissue, which eventually contracts, leaving a small scar
What is granulation tissue? What does it consist of?
Consists of loops of capillaries, myofibroblasts, collagen and inflammatory cells
What feature most clearly differentiates primary and secondary healing?