case 4 Flashcards
1
Q
What happens in the absence of food
A
occasional burst of intense activity called a
Migrating Motor Complex (M.M.C.) from
stomach - S.I. (stimulated by motilin) - Empties stomach of large particulates
- removes “sloughed off” epithelial cells
- prevents bacteria in colon moving into S.I
2
Q
small intestinal reflexes
A
Ileogastric (“ileal Break”):
Glucose & Fat in ileum gastric motility
Gastro-colic:
gastric distension colon motility (defecation)
Gastro-ileal:
gastric distension ileal motility +
ileocaecal valve relaxes
Ileocaecal valve (between small and large intestine)
- normally closed
Opens – peristaltic wave reaches it
- as part of gastroileal reflex
3
Q
opioids and gut function
A
Constipation = side effect of opiates • Opioid receptors (μ, δ, κ) in gut: enteric nerves, muscle & epithelia • Receptor activation: – Activates K+ channels – Inhibits Ca2+ channels – Inhibits cAMP production motility secretion
4
Q
why does holistic care matter
A
Aid understanding of clinical problems
Improve relationship between healthcare
professionals and patients
Increase compliance
Increase satisfaction from patients and from
healthcare providers
Increasingly patient experience is used to develop
services and measure outcomes
5
Q
what is palliative care
A
an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical,
psychosocial and spiritual.
6
Q
what level is the duodenojejunal junction
A
L2
7
Q
which parts of the large instestine are intra or retroperitoneal
A
Ceacum: intraperitoneal.–Appendix: intraperitoneal.–Ascending colon: retroperitoneal.–Transverse colon: intraperitoneal.–Descending colon: retroperitoneal in 2/3rds of humans.–Sigmoid colon: intraperitoneal.–Rectum: intraperitoneal.
8
Q
what are epiploic appendages
A
small punches of peritoneum filled with fat.Along colon and upper part of rectum.Can become inflamed.
9
Q
tenia coli
A
= 3 separate longitudinal ribbons of smooth muscle: mesocolic, free and omental coli.They contract lengtgwise to form hustra.
10
Q
McBurneys point
A
name given to the point over the right side of the abdomen that is one-third of the distance from theanterior superior iliac spineto the umbilicus(navel).This point roughly corresponds to the most common location of the base of the appendix where it is attached to thececum
11
Q
ileocecal valve
A
Remains closed most of the time.–Opens briefly to let the contents of the small intestine exit.–Closes again quickly to prevent any materials in the large intestine from leaking back.
12
Q
functions of the colon
A
- Absorption of water and electrolytes from the chyme to form solid faeces.
- Storage of faecal matter until it can be expelled.
• The proximal half of the colon is concerned primarily with absorption.
• The distal half of the colon is concerned primarily with storage.
• Intense colon wall movements aren’t required for the functions of the colon, and so the movements of the colon are normally very sluggish.
13
Q
lymphatic drainage of the abdominal organs
A
Sup/inf pancreatoduodenal, mesocolic, right L gastric, hepatic, splenic, sup inf mesenteric —coeliac–intestinal trunk–cisterna chyli–thoracic duct.
14
Q
large intestine histology
A
Mucosa–Columnar epithelium- large number of mucus secreting goblet cells.–No villi. –Appendix= MALT.•Submucosa–Meissner’s/Submucosal Plexus. •Muscularis Propria–Circular & longitudinal muscles. –Myenteric (Auerbach’s) plexus. –Teniae coli- bands of outer longitudinal muscles.•Serosa
15
Q
mixing movements (haustrations) - segmestation
A
2.5cm of circular muscle contracts, occasionally constricting the lumen closed. also the longditudinal musc - teniae coli contracts. This causes the unstimulated part to bulge out into haustrations. provide minor propulsions of colonic contents. after a few mins new haustral contractions occur so faecal material is dug into and rolled over-exposed tk mucosal surface and fluid are absorbed.
16
Q
how much faeces in expelled each day
A
80-200ml.
17
Q
propulsive movements/mass
A
in cecum and ascending result from slow haustral contractions. 8-15 hours to move chyme from ileocecal valve through colon. from cecum to sigmoid mass movements can take over propulsion. Only occur 1-3 a day.
Mass movement is modified peristalsis
18
Q
sequence of events for mass movement
A
constrictive ring occurs in responce to distended part of colon, usually in transverse, rapidly, the 20 or more centimetres of colon distal to the constrictive ring lose their haustrations and instead contract as a unit, propelling the faecal material in this segment en masse further down the colon. When they have forced a mass of faeces into the rectum, the desire for defecation is felt.
19
Q
small intestinal reflexes
A
- Ileogastric reflexes: distention of ileum leased to decreased gastric motility.
- Gastro-ileal reflexes: increased gastric distention leads to increased ileal motility and ileocaecal valve relaxes.
- The ileocaecal valve is normally closed. It opens (gastroileal reflex) when a peristaltic wave reaches it.
20
Q
regulation of peristaltic contractions
A
slow waves determine frequency, basic electrical rhythm. Resting potential of -40 to -60mV. size of slow wave modulated nerves and hormones. contraction of smooth and striated muscle in intestinal wall will only occur if potential of slow wave exceeds threshold. then voltage gated Ca channels open inc Ca inc contraction.
21
Q
interstitial cells of Cajal
A
pacemaker cells in GI. create slow waves that lead to contraction of smooth muscle.
22
Q
modulation of slow waves
A
Food stimulates nerve and hormonal activity:
Increase or decrease size of the maximum depolarisation.
Nerves (intrinsic & extrinsic)
ACh, Substance P depolarisation (= contraction)
NO, VIP, opioids hyperpolarisation (= ↓ contraction)
Noradrenaline hyperpolarisation (= ↓ contraction)
Hormones
Motilin depolarisation (= contraction)
Secretin, G.I.P. hyperpolarisation (= ↓ contraction)
Adrenaline hyperpolarisation (= ↓ contraction)
23
Q
enterochromaffin cells
A
main mechano and chemo sensory cells. Stimulation causes release of seratonin intracellularly, stimulates sensory nerves via 5-HT3 receptors. diff stimuli cause stim or inhibitory responses to parasymp NS. SERT removes seratonin to terminate signal.
24
Q
defacation
A
most of the time rectum is empty because of A weak functional sphincter which exists between the sigmoid colon and the rectum, therefore preventing the entry of food into the rectum.
The sharp angulation at the junction between the sigmoid colon and the rectum that contributes additional resistance to filling of the rectum.
When a mass movement forces faeces into the rectum the desire to defecate occurs including reflex contraction of the rectum and relacation of anal sphincters.
25
how is continual dribble of feacal matter through anus prevented
by tonic constriction of:
1. An internal anal sphincter, a several-centimetres-long thickening of the circular smooth muscle that lies immediately inside the anus
2. An external anal sphincter, composed of striated voluntary muscle that both surrounds the internal sphincter and extends distal to it.
o The external sphincter is controlled by nerve fibres in the pudendal nerve, which is part of the somatic nervous system and therefore is under voluntary, conscious or at least subconscious control; subconsciously, the external sphincter is usually kept continuously constricted unless conscious signals inhibit the constriction.
26
defacation reflex-intrinsic
intrinsic reflex mediated by local enteric NS in rectal wall. When faeces enter the rectum, distention of the rectal wall initiates afferent signals that spread through the myenteric plexus to initiate peristaltic waves in the descending colon, sigmoid, and rectum, forcing faeces toward the anus.
As the peristaltic wave approaches the anus, the internal anal sphincter is relaxed by inhibitory signals from the myenteric plexus; if the external anal sphincter is also consciously, voluntarily relaxed at the same time, defecation occurs.
The intrinsic myenteric defecation reflex functioning by itself normally is relatively weak.
27
parasympathetic defacation reflex
needed for effective defacation. involves sacral segments of the spinal cord. When the nerve endings in the rectum are stimulated, signals are transmitted first into the spinal cord and then reflexly back to the descending colon, sigmoid, rectum, and anus by way of parasympathetic nerve fibres in the pelvic nerves.
These parasympathetic signals greatly intensify the peristaltic waves as well as relax the internal anal sphincter, thus converting the intrinsic myenteric defecation reflex from a weak effort into a powerful process of defecation that is sometimes effective in emptying the large bowel all the way from the splenic flexure of the colon to the anus.
28
what other effects does defecation signals entering the spinal cord initiate
Taking a deep breath
Closure of the glottis
Contraction of the abdominal wall muscles to force the faecal contents of the colon downward and at the same time the pelvic floor is relaxed downward and pull outward on the anal ring to evaginate the faeces
29
how can defacation reflexes be purposfully activated
taking a deep breath to move the diaphragm downward and then contracting the abdominal muscles to increase the pressure in the abdomen, thus forcing faecal contents into the rectum to cause new reflexes.
• Reflexes initiated in this way are almost never as effective as those that arise naturally, for which reason people who too often inhibit their natural reflexes are likely to become severely constipated.
30
what influences rate of secretion of mucus
direct, tactile stimulation of the epithelial cells lining the large intestine and by local nervous reflexes to the mucous cells in the crypts of Lieberkühn.
• Stimulation of the pelvic nerves from the spinal cord, which carry parasympathetic innervation to the distal one half to two thirds of the large intestine, also can cause marked increase in mucus secretion.
This occurs along with increase in peristaltic motility of the colon.
31
what can emotional disturbances do to mucis
• During extreme parasympathetic stimulation, often caused by emotional disturbances, so much mucus can occasionally be secreted into the large intestine that the person has a bowel movement of ropy mucus as often as every 30 minutes; this mucus often contains little or no fecal material.
32
functions of mucus in the large intestine
Protects the intestinal wall against excoriation.
Provides an adherent medium for holding faecal matter together.
Protects the intestinal wall from the great amount of bacterial activity that takes place inside the faeces.
Plus the alkalinity of the secretion (pH of 8.0 caused by large amounts of sodium bicarbonate) provides a barrier to keep acids formed in the faeces from attacking the intestinal wall.
33
Diarrhea Caused by Excess Secretion of Water and Electrolytes in Response to Irritation
* Whenever a segment of the large intestine becomes intensely irritated, as occurs when bacterial infection becomes rampant during enteritis, the mucosa secretes extra large quantities of water and electrolytes in addition to the normal viscid alkaline mucus.
* This acts to dilute the irritating factors and to cause rapid movement of the faeces toward the anus.
* The result is diarrhoea, with loss of large quantities of water and electrolytes.
* But the diarrhoea also washes away irritant factors, which promotes earlier recovery from the disease than might otherwise occur.
34
where is Cl- secreted
* Electrogenic Cl- secretion occurs in crypts of both the small and the large intestine. • Cl- secretion is markedly stimulated by secretagogues such as ACh and other neurotransmitters.
* Cl- secretion is the major component of the ion transport events that occur during most diarrhoeal disorders.
35
three transport pathways on the basolateral membrane for Cl-
1. Na-K pump
2. Na/K/Cl cotransporter
3. Two types of K+ channels (IK1 and BK1)
• In addition, a Cl- channel (cystic fibrosis transmembrane regulator (CFTR)) is present on the apical membrane.
36
how is the Cl- secretory system energized
by the Na-K pump, which generates a low [Na+]i and provides the driving force for Cl− entry across the basolateral membrane through Na/K/Cl cotransport.
• As a result, [Cl−]i is raised sufficiently that the Cl− electrochemical gradient favors the passive efflux of Cl− across the apical membrane.
37
consequence of the many transport processes
the transepithelial voltage becomes more lumen negative, thereby promoting voltage-dependent Na+ secretion.
• This Na+ secretion that accompanies active Cl− secretion presumably occurs through the tight junctions (paracellular pathway).
• Thus, the net result is stimulation of NaCl and fluid secretion.
38
what does Cl- secretion require
• Normally (i.e., in the unstimulated state), the crypts secrete little Cl− because the apical membrane Cl− channels are either closed or not present.
• Cl− secretion requires activation by cyclic nucleotides or [Ca2+], which are increased by any of several secretagogues:
1. Bacterial exotoxins (i.e. enterotoxins)
2. Hormones and neurotransmitters
3. Products of cells of the immune system (e.g. histamine)
4. Laxatives
39
K ion secretion
• Passive K+ secretion is the primary mechanism for net colonic secretion.
• Active K+ secretion is present throughout the large intestine and is induced both by aldosterone and by cAMP.
• K+ ions can be both passively and actively secreted.
• Active transport of K+ ions is subject to considerable segmental variation in the colon.
Whereas active K+ secretion occurs throughout the colon, active K+ absorption is present only in the distal segments of the large intestine.
Thus, in the recto-sigmoid colon, active K+ absorption and active K+ secretion are both operative and appear to contribute to total body homeostasis
40
active K+ secretion
Uptake of K+ across the basolateral membrane is a result of both the Na-K pump and the Na/K/Cl cotransporter (NKCC1), which is energized by the low [Na+]i that is created by the Na-K pump.
Once K+ enters the cell across the basolateral membrane, it may exit either across the apical membrane (K+ secretion) or across the basolateral membrane (K+ recycling).
The cell controls the extent to which secretion occurs, in part by K+ channels present in both the apical and the basolateral membranes.
When apical K+ channel activity is less than basolateral channel activity, K+ recycling dominates.
Indeed, in the basal state, the rate of active K+ secretion is low because the apical K+ channel activity is minimal in comparison with the K+ channel activity in the basolateral membrane. • Aldosterone stimulates active K+ secretion in surface epithelial cells of the large intestine, whereas cAMP enhances active K+ secretion in crypt cells.
In both cases, the rate-limiting step is the apical BK K+ channel, and both secretagogues act by increasing K+ channel activity.
41
how does aldosterone increase K+ secretion
increases passive K+ secretion by increasing Na-K pump activity and thus increasing electrogenic Na+ absorption.
The net effects are to increase the lumen-negative VTE and to enhance passive K+ secretion.
2. Second, aldosterone stimulates active K+ secretion by increasing the activity of both apical K+ channels and basolateral Na-K pumps
42
cAMP, Ca+ effect on K+
VIP and cholera enterotocin inc cAMP so stim K, Ca also stim active K secretion in both apical and basolateral channels.
• Because the stimulation of K+ channels is greater at the apical than at the basolateral membrane, the result is an increase in K+ secretion from the epithelial cell across the apical membrane.
• Stimulation of K+ secretion by cAMP and Ca2+, both of which also induce active Cl− secretion, contributes to the significant faecal K+ losses that occur in many diarrheal diseases.
43
absorption in large intestine: formation of feaces
* Most of the water and electrolytes in the chyme are absorbed in the colon, usually leaving less than 100ml of fluid to be excreted in the faeces.
* Nearly all the ions are absorbed, leaving only 1-5mEq each of sodium and chloride ions to be lost in the faeces.
* Most of the absorption in the large intestine occurs in the proximal half of the colon, giving this portion the name absorbing colon, whereas the distal colon functions principally for faeces storage until a propitious time for faeces excretion and is therefore called the storage colon.
44
absorptions of Na
activley transported, Na/k, Na/k/Cl, in ileum and LI. causes electrical potential gradiant which causes Cl absorbtion too. Tight junctions very tight so small back diffusion. • The overall electroneutral NaCl absorptive process is regulated by both cAMP and cGMP, as well as by intracellular Ca2+.
• Increases in each of these three intracellular messengers reduce NaCl absorption.
• Decreases in [Ca2+]I increase NaCl absorption.
• Decreased NaCl absorption is important in the pathogenesis of most diarrheal disorders.
45
Epithelial Na+ Channels and Distal Colon
* Epithelial Na+ channels are the primary mechanism of electrogenic Na+ absorption in the distal part of the colon.
* In electrogenic Na+ absorption, Na+ entry across the apical membrane occurs through epithelial Na+ channels (ENaCs) that are highly specific for Na+.
* These ENaCs are blocked by the diuretic amiloride (a potassium sparing diuretic).
* Na+ absorption in the distal part of the colon is highly efficient.
* Because this segment of the colon is capable of absorbing Na+ against large concentration gradients, it plays an important role in Na+ conservation.
* Na+ movement through electrogenic Na+ absorption is markedly enhanced by mineralocorticoids (e.g aldosterone).
* Aldosterone increases electrogenic Na+ absorption by increasing Na+ entry through the apical Na+ channel and by stimulating activity of the Na-K pump.
46
voltage dependant Cl absorption
o Cl− may passively diffuse from lumen to blood across the tight junctions, driven by the lumen-negative transepithelial voltage (paracellular route).
o Alternatively, Cl− may diffuse through apical and basolateral Cl− channels.
o This usually occurs in the jejunum, ileum and the distal colon.
47
electroneutral Cl HCO3 exchange
o In the absence of a parallel Na-H exchanger, electroneutral Cl-HCO3 exchange at the apical membrane results in Cl− absorption and HCO3 secretion.
o This occurs in the ileum, proximal colon and the distal colon.
48
parallel Na H and Cl HCO3 exchange
o Electroneutral NaCl absorption can mediate Cl− absorption in the interdigestive period.• Absorption of sodium and chloride ions creates an osmotic gradient across the large intestinal mucosa, which in turn causes absorption of water.
49
what is the maximum absorption capacity of the large intestine
• The large intestine can absorb a maximum of 5-8 litres of fluid and electrolytes each day
50
bacterial action in the colon
colon bacilli.capable of digesting small amounts of cellulose, in this way providing a few calories of extra nutrition for the body.
This source of energy is of little importance in human beings.
• Other substances formed as a result of bacterial activity are vitamin K, vitamin B12, thiamine, riboflavin, and various gases that contribute to flatus in the colon, especially carbon dioxide, hydrogen gas, and methane.
• The bacteria-formed vitamin K is especially important because the amount of this vitamin in the daily ingested foods is normally insufficient to maintain adequate blood coagulation.
51
composition of faeces
```
¾ water
¼ solid matter
30% dead bacteria
10-20% fat
10-20% inorganic matter
2-3% protein
30% undigested roughage from the food and dried constituents of digestive juices, such as bile pigment and sloughed epithelial cells
```
52
properties of faeces
• The brown colour of faeces is caused by stercobilin, a derivative of bilirubin.
• The odour is caused by products of bacterial action; these products vary from one person to another, depending on each person’s colonic bacterial flora and on the type of food eaten.
The actual odoriferous products include indole, skatole, mercaptans, and hydrogen sulfide
53
change in size of cells
Atrophy - cell shrinking
This may be achieved by apoptosis, reduced functional activity, loss of innervation, reduced blood supply, diminished nutrition, loss of hormonal or growth factor stimulation.
Hypertrophy - increase in size of existing cells
It is accompanied by an increase in functional capacity.
The number of cells doesn’t change, the cells just get bigger
54
change in number of cells
Hyperplasia - increased number of cells caused by an increase in cell division.
Aplasia - decreased number of cells.
55
change in differentiation
Metaplasia - this is an adaptive response to environmental stimuli
Specialised cell types change their pattern of differentiation to a new mature stable cell type.
This allows them to withstand stress better
56
growth in cancer
* Metaplasia - this is an adaptive response to environmental stimuli
* Dysplasia - the enlargement of tissue by the proliferation of abnormal (metaplasia) cells, as a developmental disorder or an early stage in the development of cancer.
* Anaplasia - loss of intracellular structural differentiation within a cell often with increased capacity for multiplication, as in a malignant tumour.
* Cancer>metaplasia followed by dysplasia followed by anaplasia.
57
cell cycle - interphase
G1-normal cell functions + cell growth, duplication of organelles.
This is the phase where the cell is sensitive to growth factors (thus entering cell cycle) and anti-proliferative factors (thus not entering cell cycle). Once the cell has entered the cell cycle, there is no reversal – the point at which the cell enters the cell cycle and can no longer be affected by growth/anti-proliferative factors, is called the ‘restriction point'.
G0 – Cells that stay in G1 for a long time, and possibly never divide again are said to be in G0
S phase (synthesis phase) – DNA replication
G2 – Chromosomes begin to condense in preparation for the next mitotic division
58
Mitosis - prophase
– chromosome becomes visible, 2 pairs of centriole separate, and nucleus disintegrates.
59
Metaphase
chromatids move to a midline (equator)
60
anaphase
– Chromatids are pulled apart
61
telophase
Chromosomes uncoil, two nuclei formed
62
cytokinesis
Cytoplasmic division
63
cell cycle control
* Cyclins activate Cyclin Dependent Kinases (CDKs) – these are enzymes that control the progression through the cell cycle - checkpoint control.
* Checkpoint controls prevent DNA replication or mitosis of damaged cells and either stop the cell cycle to allow for DNA repair or eliminate irreversibly damaged cells by apoptosis.
* CDKs work by promoting DNA replication and various aspects of the mitotic process and are required for cell cycle progression.
* Cyclin Kinase Inhibitors (CKIs) inhibit CDKs.
* One particular CKI is p21, which is a potent inhibitor of CDKs
64
cell cycle cyclins and CDKs
D E A A B
| 4 2 2 1 1
65
cyclin B
protein found in high quantities in the late G2 stage, peaking during mitosis.
• It associates with cyclin-dependent kinase (CDK1) to activate it.
• Cylin B/CDK1 complex phosphorylates proteins to cause mitosis.
• MAP: microtubule associated proteins – cause spindle formation.
• Lamin: usually makes a protein meshwork which the nuclear envelope sits on. Upon phosphorylation, this meshwork breaks down, leading to the breakdown of the nuclear envelope.
• Histone: this causes condensation of chromosomes.
66
signalling pathways
ligand-receptor-signalling cascade-transcription factors-gene expression-proteome-tissue function/architecture altered
67
Ras and cell signalling
normally bound to GDP and is inactive. GTP makes active-now can initiate signalling cascades to causes inhibition of apoptosis, cell growth, protein synthesis etc. It is an oncogene, its mutation causes it to remain active and cause inc in cell growth and proliferation.
68
Wnt signalling
signalling pathway must be mutated to cause colorectal cancer! Wnt is a ligand. Absense, GSK-3B is active so phosphorylates beta catenin, which causes proteolytic degradation of B catenin. When Wnt signals are present, bind receptor and GSK-3B is switched off so B catenin isnt phosphorylated so not degraded, It moves into nucleus where interacts with transcription factors changing gene expression and increasing cell proliferation. A mutation in B catenin gene causes it to remain unphosphorylated and stable so incereases cell proliferation.
69
cell cycle entry
* Growth factors stimulate Ras, which binds to its receptors, thus activating transcription factors and affecting gene expression, especially Cyclin D1.
* Wnt signals, via B-catenin, also activate transcription factors, and affect gene expression, especially Cyclin D1.
* Cyclin D1 activates CDK4.
* CDK4 phosphorylates Rb = pRb.
* Normally Rb binds to the E2F family of transcription factors, it inhibits them.
* When CDK4 phosphorylates Rb, pRb now causes the liberation of E2F transcription factors, thus allowing them to enter the nucleus and modulating gene expression, especially of Cyclin E.
* Cyclin E can now bind to its CDK (CDK2), thus triggering the S phase of the cell cycle.
70
cells in the SI effected by Wnt
principle cell type of epithelium of SI are Paneth cells. Found below stem cells in crypts. Belong to stem cell niche which is a microenviron where stem cells are found where they are influenced by growth (Wnt) and differentiating factors to regulate cell fate.
71
Rb
tumour suppressor gene.
• If one copy of this gene is mutated, it has no effect on the liberation of E2F.
• However, if both copies of Rb are mutated, then E2F is always liberated and the cell continuously enters the cell cycle and the S phase without the importance of the checkpoint control.
72
S phase
all the control of the cell cycle happens internally, i.e. external factors don’t influence this phase of the cycle.
• Here, the stability of the genome is maintained without any damage to the DNA.
• If the S phase doesn’t go as planned, it results in the activation of p53, which will then aim to shut down the cell cycle (defense mechanism).
• P53 is a transcription factor which is degraded normally, but in response to stimuli it can become active and remains non-degraded.
Kinases and ubiquitin ligases which would normally break down p53 are inhibited
73
activation of p53
• Activation of p53 can be as a result of:
```
Lack of nucleotides
UV radiation
Ionizing radiation
Oncogene signalling
Hypoxia
Blockage of transcription factors
```
74
activation of p53 causes the following cascades
Cell cycle arrest, leading to senescence or return to proliferation.
This occurs by the upregulation of p21 (CKI).
This inhibits CDKs, thus arresting the cell cycle.
DNA repair
Block of angiogenesis
Apoptosis
P53 drives expression of genes such as Puma and Noxa.
These activate the BAX intrinsic apoptotic pathway, thus leading to programmed cell death.
Bcl-X is a pro-survival protein in colon cancer.
75
apoptosis
programmed cell death. intracellular events causing cell death without release of products harmful to surrounding cells. Ex/Intrinsic pathways.
76
proteolytic cascade for apoptosis
1. Cell shrinks and condenses. pyknosis
2. Digestion of the nuclear DNA into small DNA fragments. Karyorrhexis.
3. Cell’s cytoskeleton disassembles.
4. Blebbing.
5. Cell surface membrane altered to allow phagocytosis.
77
extrinsic pathway for apoptosis
* Ligand (TNFα or Fas) bind to a receptor on the cell surface membrane of the cell.
* The activation of the receptor causes a DISC (death inducing signaling complex) to bind to the internal aspect of the receptor.
* This causes the activation of enzymes known as caspases (known as paracaspases when inactivated).
* Proteolytic cascade occurs.
78
Intrinsic pathway
* Cell recognises internal damage.
* BAX (in the cytoplasm) binds to a receptor on the mitochondria.
* Upon binding, BAX changes shape.
* Proteins (cytochrome C) in the intramembranous space of the mitochondria leak out into the cytoplasm.
* Cytochrome C activates the paracaspases into caspases, leading to apoptosis.
79
necrosis
• Cell death due to:
1. Trauma
2. Disease
3. Ischaemia as a result of lack of blood supply
• Release of intracellular content into the surrounding tissue
80
familial cancers
1% of all cancers.
Single gene mutations (Mendelian disorders)
Most are inherited as autosomal dominant traits.
Most due to inherited mutations of tumour suppressor genes.
Further genetic events are necessary if the mutation is in somatic cells. Even though the mutated gene is inherited, it isn’t sufficient for malignancy.
The inherited mutated gene increases cancer susceptibility
Early onset, multiple tumours, both copies of TSG inactivated in tumour cell, in other cells one copy of TSG inactivated
81
sporadic cancers
99% of all cancers.
Result of exposure to carcinogenic agents and unrepaired DNA replication errors.
Results in somatic activation/ inactivation of cancer genes
Late onset, single tumour usually, tumour cells both copies of TSG inactivated all other cells normal.
82
general types of cancer
* Adenoma: cancer of the glands (glandular cells)
* Carcinoma: epithelial cells (more than 90% of all cancers)
* Lymphoma: lymphocytes or lymphatic system
* Sarcoma: connective tissue
* Blastoma: immature/ pre-cursor cells (dendrites – white blood cells)
* Papilloma: surface epithelia (skin)
83
neoplasia
means new growth-tumour, described as malignant
84
Benign tumours
capsule surrounding tumour, well differentiated cells, structure similar to tissue organ, Low mitotic activity-slow rate of growth, no invasion or metastasis.
85
malignant tumours
no capsule, lack differentiation (anaplasia) structure different to tissue organ, high mitotic activity, invasion and metastasis.
86
genomic instability
• Cancer genomes are unstable:
Either chromosomal instability (CIN) – result of many numerical and structural abnormalities.
Or microsatellite instability (MIN) – result of impaired DNA Mismatch Repair (MMR).
87
telomerase and senescence
* Telomerase is an enzyme that prevents the shortening of the telomere, thus preventing senescence (specific number of cell divisions).
* In normal cells, telomerase is switched off.
* In malignant cells, telomerase is switched on, thus inhibiting senescence.
88
successful carcinogenesis
• Successful carcinogenesis requires:
Either mutations that increase the rate of cell proliferation, so as to provide an expanded target for further mutations (clonal evolution).
Or mutations that destabilise the genome, so as to increase the rate of further mutations.
89
successful malignant cells
become independant of external growth signals. Insensitive to external antigrowth signals. Avoid apoptosis. Indefinite replication-usually have finite number before dying-senescence. Sustained angiogenesis. Metastasis.
90
cancer is mediated by
```
Genes – oncogenes and TSGs
Telomeres – telomerase and senescene
Signalling Pathways – Wnt and Ras
Genome Instability – CIN/ MMR
P53 and Apoptosis
Cell Cycle Control – cyclin/ CDK/CKI(p21)/
```
91
(proto)oncogenes
Gain function, dominant. can be activated to oncogene due to mutations or inc expression. result Protein-oncoprotein. they promote cell devision survival and growth.
92
Tumour suppressor gene
Loss of function, recessive. • Tumour suppressor genes are the body’s natural defence mechanism against malignancy.
• When both alleles of this gene are mutated, there is a loss in protein function.
• If there is a familial predisposition, then one allele has already been mutated, therefore, only a second hit is required for fatal effects (“two-hit hypothesis”).
• Inactivation of TSGs are caused by:
1. Mutations
2. Chromosomal abnormalities
3. Methylation of promoters
4. Interaction with viral proteins
• Loss of TSG is worse than activation of oncogenes!!!
93
activation of protooncogenes
1. Point mutations that increase protein function.
2. Gene amplification that causes overexpression.
3. Chromosomal translocation (e.g. MYC).
4. Viral stimulation that may lead to addition/deletion of genes when viral DNA is integrated with human DNA
• Example: MYC - This is a regulator gene that codes for a transcription factor. If translocated, MYC will be continually expressed, causing unregulated expression of many genes, some of which are involved in cell proliferation (e.g. cyclin D1) and results in the formation of cancer.
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oncogene
potential to cause cancer (e.g. β-catenin and KRAS)• Oncogenes usually code for:
1. Secreted growth factors (e.g. EGF/ Wnt/ Ras)
2. Cell surface receptors (e.g. HER)
3. Signal transduction system components (ABL)
4. Nuclear proteins, transcription factors (e.g. MYC)
5. Cyclins/ cyclin-dependent kinases (cyclin D1, CDK4)
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functions of tumour suppressor genes
1. Inhibit progression through the cell cycle (CDKIs = p21)
2. Promote apoptosis (e.g. p53 gene and APC).
3. Inhibit cell growth (anti-proliferative).
4. DNA repair and genomic stability (mismatch DNA repair genes (replication error genes) and BRCA1 gene).
5. Cell adhesion to prevent metastasis
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all cancers metastasise except
1. Glial cells of the CNS (these usually form benign tumours)
2. Basal cell carcinomas of the skin
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cancer spreads by 3 pathways
1. direct seeding of body cavities or surfaces (local invasion of surrounding tissue)
2. lymphatic spread
3. hematogenous spread (blood)
• Common metastasis sites: lungs, liver, spine and bone
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colorectal cancer
cancer in the colon or rectum-large intestine. abnormal growth of cells that can invade other parts of the body. usually an adenocarcinoma. mostly sporadic. some familial-FAP/HNCC.
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epidemiology of Colorectal cancer
3rd most common cancer and 2nd most common cause of UK cancer deaths (16,000 deaths/ year).
56% of presentations are in those >70 years old.
15% caecum and ascending colon
10% transverse colon
5% descending colon
25% sigmoid colon
45% rectum
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risk factors of Colorectal cancer
diet-red and processed meats. N nitros compounds NOCs which are carcinogenic. Low fibre doesnt use muscles as much. Obesity. Smoking, Alcohol. over 50. family history - neoplastic adenomatous polyps, colorectal cancer. Inherited disease FAP HNCC. History of inflammatory bowel disease.
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presentation: left sided cancer, disorder with storage
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o Bleeding/ mucus (PR)
o Altered bowel habit or obstruction (25%)
o Tenesmus (continual feeling of needing to evacuate bowel)
o Mass (PR)
o Abdominal mass
o Perforation
o Haemorrhage
o Fistula
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presentation: right sided cancer, disorder with absorption
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o Weight loss
o Reduced haemoglobin
o Abdominal pain
o Obstruction less likely
o Abdominal mass
o Perforation
o Haemorrhage
o Fistula
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tests for colorectal cancer
Blood Test
Full blood count – indicate low serum levels (microcytic anaemia)
Serum proteins –
Calcium – check for metastatic hypercalcemia (bone metastasis)
Liver Function Test
Bilirubin – colorectal cancer liver metastasis causes severe hyperbilirubinaemia
Alkaline phosphatase (ALP) – ALP levels elevated with liver metastasis of colorectal cancer
Kidney Function Test
Creatinine – creatinine levels elevated with kidney metastasis of colorectal cancer
Sigmoidoscopy/ Colonoscopy/ Barium enema
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colorectal cancer investigations
• For patients without major comorbidity – offer colonoscopy to confirm diagnosis of colorectal cancer.
• For patients with major comorbidity – offer flexible sigmoidoscopy then barium enema.
If a lesion suspicious of cancer is detected, perform a biopsy to obtain histological proof of diagnosis, unless it is contraindicated (for example, patients with a blood clotting disorder).
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endoscopy
1. Sigmoidoscopy – the endoscope only reaches to the top of the descending colon
2. Colonoscopy – the endoscope reaches the entire length of the colon to the ileocecal valve
• Both these allow the doctor to view the mucosal lining of the lower GI.
• Before a colonoscopy procedure:
IV pain medication and sedative
Blood pressure, pulse and oxygen monitored
Supplemental oxygen
• A sigmoidoscopy doesn’t require this much preparation.
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barium enema
* Barium enema – this is a test used to identify problems in the colon, such as polyps, inflammation (colitis), narrowing of the colon, tumours etc.
* A thick liquid (containing barium) is placed in the lower gut via the rectum.
* This coats the mucosal lining of the colon, thus highlighting the colon in an x-ray.
* Characteristic findings are indicative of pathology
* Colon cancer leaves an “applecore” sign
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analysing faeces
help diagnose conditions of the GI like infection (parasites, viruses, orbacteria), poor nutrient absorption, or cancer. Laboratory analysis includes microscopic examination, chemical tests, and microbiologic tests.
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colorectal cancer treatment-surgery
cure and increase survival times by up to 50%.
• Laparoscopic surgery is a safe alternative to an open approach.
• Right Hemicolectomy - for caecal, ascending or proximal transverse colon (2/3) tumours (midgut)
• Left Hemicolectomy – for tumours in distal transverse colon (1/3) or descending colon (hindgut)
The reason they perform it with regards to ‘midgut’ and ‘hindgut’ is so that the area with the same blood supply is removed.
• Anterior Resection – for low sigmoid or high rectal tumours.
• Abdomin-perineal (A-P) Resection – for tumours in low rectum: permanent colostomy and removal of rectum.
• Hartmann’s Procedure – in emergency bowel obstruction or palliation
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radiotherapy
* Radiotherapy may be used pre-op in rectal cancer to reduce the local recurrence and increase 5 year survival.
* It may be associated with a higher rate of post-operative complication, e.g. DVT.
* Pre-op radiotherapy is only used in patients with rectal tumours at high risk of local recurrence
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chemotherapy
* Good evidence adjuvant fluorouracil (5-FU) and other agents (e.g. folinic acid, levamisole).
* Chemotherapy reduces Duke’s C mortality by about 25%.
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Fluorouracil 5-FU
* Fluorouracil is a pyrimidine analog that is an antineoplastic antimetabolite.
* An antimetabolite prevents purine/pyramidine (e.g. thymine) from incorporating into the DNA during the “S” phase, stopping normal development and division.
* Fluorouracil blocks the enzyme which converts the cytosine nucleotide into the deoxy derivative.
* Fluorouracil inhibits the incorporation of the thymidine (a pyrimidine) nucleotide into the DNA strand.
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mechanism of Fluorouracil
Fluorouracil is converted in cells to 5-fluoro-2’-5’-monophosphate (5-FdUMP) and 5-fluorouridine-5’-triphosphate (FUTP), its metabolites.
5-FdUMP incorporates into the DNA of fast growing cells in the body.
Here, it interferes with DNA synthesis by blocking thymidylate synthetase.
Normally, thymidylate synthetase converts uracil into thymidylate.
Blocking this enzyme inhibits the synthesis of thymidylate.
This means that thymidine (a pyrimidine) can no longer be incorporated into DNA.
Incorporation of FdUMP into DNA inhibits DNA synthesis function.
Incorporation of FUTP into RNA interferes with RNA processing and function.
Tumour cell resistance mechanisms include decreased activation of 5-FU, increased thymidylate synthase activity, and reduced drug sensitivity of this enzyme.
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folinic acid
• This is generally administered as calcium or sodium folinate (or leucovorin calcium/sodium).
• It is an adjuvant used in cancer chemotherapy involving the drug methotrexate.
• It is also used in synergistic combination with chemotherapy agent 5-FU.
• Folinic acid can be taken as a pill or injected into a vein (intravenously) or muscle.
• Indications:
Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anaemias due to folic acid deficiency.
Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer. It enhances the effect of 5-FU by inhibiting thymidylate synthase.
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folinic acid mechanism
As leucovorin is a derivative of folic acid, it can be used to increase levels of folic acid under conditions favouring folic acid inhibition (following treatment of folic acid antagonists such as methotrexate).
Leucovorin enhances the activity of fluorouracil by stabilizing the bond of the active metabolite (5-FdUMP) to the enzyme thymidylate synthetase.
This is because 5-FU doesn’t stay long in the system and so folinic acid allows 5-FU to bind to this enzyme.
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TNM staging
T-tumour. 0 in situ, in mucosa. T1 into submucosa. T2 grown into muscle layer of bowel. T3 grown into outer lining of bowel (serosa) T4 Grown through outer wall, nearby structures then finally perforation and to outside bowel.
N0 no nodes, N1 3 nodes, N2 4+ nodes.
M0 no metastasis. M1 distant metastasis.
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Dukes staging for colorectal cancer
* This provides a 5 year prognosis.
* Dukes’ A: 90% chance of survival over the next 5 years.
* Dukes’ B: 66% chance of survival over the next 5 years.
* Dukes’ C: 33% chance of survival over the next 5 years.
* Dukes’ D:
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number staging for colorectal cancer
Stage 0
• The cancer is at its earliest stage and is only in the mucosa (Tis N0 M0).
Stage 1
• The cancer has grown into the submucosa or muscle but has not spread to the lymph nodes or elsewhere (T1 N0 M0 or T2 N0 M0).
Stage 2
• The cancer has grown through the muscle wall or through the outer layer of the bowel, and may be growing into tissues nearby. The cancer has not spread to the lymph nodes or elsewhere (T3 N0 M0 or T4 N0 M0).
Stage 3
• The tumour is any size and has spread to lymph nodes nearby, but has not spread anywhere else in the body (Any T N1 or N2 M0).
Stage 4
• The tumour is any size. It may have spread to nearby lymph nodes. The cancer has spread to other parts of the body such as the liver or lungs (Any T Any N M1).
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grading of cancer
• Grading refers to how closely the tumour cells resemble their tissue of origin; level of malignancy is based on cytological differentiation (dysplasia and anaplasia) of tumour cells and the number of mitoses within the tumour. Grade 3 is look abnormal and proliferate rapidly.
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types of mutation
Missense mutations
With a missense mutation, the new nucleotide alters the codon so as to produce an altered amino acid in the protein product. Nonsense mutations
With a nonsense mutation, the new nucleotide changes a codon that specified an amino acid to one of the STOP codons.
Silent.
Translocations are the transfer of a piece of one chromosome to a nonhomologous chromosome. Translocations are often reciprocal; that is, the two nonhomologues swap segments
Deletion, inseriton, frameshift.
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pathology of colon cancer
* The mucosal lining of the colon contain crypts.
* These are the sites of mutations in colon cancer.
* If the mutation occurs in the differentiated villi/ epithelial cells, then the development of the tissue isn’t so harmful.
* If the mutation occurs in the crypts (the site of colon stem cells), then the development of the tissue is very harmful (polyps).
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FAP and APC
* Adenomatous Polyposis Coli (APC) forms part of the Wnt Signalling pathway, APC formed part of the intracellular protein complex.
* APC gene is a tumour suppressor gene.
* APC gene encodes a protein consisting of 2800 amino acids which binds to B-catenin, thus causing down regulation of it by initiating its proteolytic degradation (along with activated GSK-3B).
* This stops the cell from over proliferating.
• A mutation in APC:
1. Prevents the degradation of B-catenin and so results in excessive proliferation of the cell.
2. Makes the genome unstable by affecting the spindling during mitosis.
3. Stimulates the migration of malignant stem cells out of the crypts (polyps).
• Deregulation of APC/B-catenin is an obligate and early step in CRC.
* APC IS MUTATED IN 80-90% OF SPORADIC COLORECTAL CANCERS!
* B-CATENIN IS MUTATED IN 10-20% OF SPORADIC COLORECTAL CANCERS!
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HNCC
* This is an inherited disease of the colon that causes about 2-3% of all colorectal cancers.
* It is also known as ‘Lynch syndrome’.
* HNCC not only predisposes the individual to colorectal cancer, it predisposes them to other cancers too (ovarian, small intestine, urinary tract, skin and brain).
* In this condition, very few polyps form but the progression of development into colorectal cancer is fast (2-3 years).
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mismatch repair
• Mismatch repair genes have a higher mutation rate than other genes.
• If mismatch genes are mutated then any errors in newly made DNA strands can’t be repaired.
• This leads to an increase in mutations newly made DNA strands.
E.g. MLH1 gene is a mismatch repair gene, associated with microsatellite stability. A mutation of this can lead to microsatellite instability and HNCC.
• MLH1 mutations can cause cancer:
The cells are constantly making mistakes when making new DNA strands that aren’t being repaired.
This means the mutation rate in these patients increases significantly.
This means that they can acquire more mutations more easily in specific regions of the genome such as oncogenes and TSGs.
An elevated mutation rate doesn’t cause cancer; mutations in specific areas of the genome give us cancer (i.e. in oncogenes/ TSGs).
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TGF B
TGF-B binds to its receptor, thus causing a signalling cascade to occur via Smad intracellular proteins.
This causes:
Activation of CKIs – thus inhibiting proliferation
Inhibition of MYC (a pro-proliferative molecule) – thus inhibiting proliferation
• Mutations can occur in the Smad 4 pathway (25% of CRC), thus leading to an increase in proliferation.
• Mismatch Repair Gene Mutation:
TGF-B is a growth inhibitory factor.
Mismatch repair mutations cause deletion of AA bases.
This causes a truncation of the TGF-B receptor gene, meaning that it is no longer synthesised.
As a result, the cell now becomes unresponsive to anti-proliferative signals (such as that from TGF-B).
TGF-B receptor gene mutation occurs in 90% of colorectal cancers with a mismatch repair gene defect.
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inflammation
• Without the TGF-B pathway (anti-proliferative effect), the colon becomes sensitised to inflammation and so can develop colorectal cancer.
• In response to the inflammatory response, the NF-kB pathway is upregulated, leading to an upregulation of gene expression, causing:
Proliferation (via Cyclin D1)
Anti-apoptosis (via Bcl-X = pro-survival protein)
Synthesis of Pro-inflammatory prostaglandins (via COX2)
NSAIDs can block this pathway.
Evidence suggests that long-term prophylactic use of NSAIDs can reduce the incidence rate of colorectal cancer
• Chronic inflammation, in this manner, causes ulcerative colitis, which increases the risk of developing colorectal cancer.
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angiogenesis
* Damage to the vasculature (due to the invasive effects of the tumour) lead to an increase in vascular endothelial growth factor (VEGF).
* This results in angiogenesis.
* Angiogenesis can be treated by VEGF-inhibitors (eg. Avastin).
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psychology in cancer
• First suggested by Galen in AD 200–300, who argued for an association between melancholia and cancer,
• Gedman in 1701 suggested that cancer might be related to life disasters.
• Eighty-five per cent of cancers are thought to be potentially avoidable.
Psychology therefore plays a role in terms of attitudes and beliefs about cancer and predicting behaviours, such as smoking, diet and screening which are implicated in its initiation
In addition, sufferers of cancer report psychological consequences, which have implications for their quality of life.
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Observations for psychology in cancer
• Cancer cells are present in most people but not everybody gets cancer; in addition, although research suggests a link between smoking and lung cancer, not all heavy smokers get lung cancer.
Perhaps psychology is involved in the susceptibility to cancer
• All those who have cancer do not always show progression towards death at the same rate.
Perhaps psychology has a role to play in the progression of cancer
• Not all cancer sufferers die of cancer.
Perhaps psychology has a role to play in longevity
• The role of psychology in cancer will now be examined in terms of:
(1) the initiation and promotion of cancer;
(2) the psychological consequences of cancer;
(3) dealing with the symptoms of cancer; and
(4) longevity and promoting a disease-free interval
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behavioural factors in initiation and promoting cancer
Smith and Jacobson (1989) reported that
30% of cancers are related to tobacco use,
35% are related to diet,
7% are due to reproductive and sexual behaviour
3 % are due to alcohol.
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stress factors
Laudenslager et al. (1983)
• If this stressor could be controlled, there would be a decrease in the rate of tumour development. However, if the stressor was perceived as uncontrollable, this resulted in an increase in the development.
Sklar and Anisman (1981)
• An increase in stress increased the promotion of cancer, not its initiation
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life events
Jacobs and Charles (1980)
• reported that in families who had a cancer victim there were
higher numbers who had moved house,
higher numbers who had changed some form of their behaviour,
higher numbers who had had a change in health status other than the cancer person,
higher numbers of divorces,
indicating that life events may well be a factor contributing to the onset of cancer
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coping styles
* If an individual is subjected to stress, then the methods they use to cope with this stress may well be related to the onset of cancer.
* For example, maladaptive, disengagement coping strategies, such as smoking and alcohol, may have a relationship with an increase in cancer
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personality
Temoshok and Fox (1984)
• Argued that individuals who develop cancer have a ‘type C personality’ (passive, appeasing, helpless, other focused and unexpressive of emotion)
Eysenck (1990)
• Described ‘a cancer-prone personality’, and suggests that this is characteristic of individuals who react to stress with helplessness and hopelessness, and individuals who repress emotional reactions to life events.
• E.g. heavy smokers who develop lung cancer have a poorly developed outlet for their emotions, perhaps suggesting type C personality.
• The type of individual who was more likely to develop cancer as having impaired self-awareness, being self-sacrificing and self-blaming, and not being emotionally expressive (16% greater risk
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hardiness
• Kobasa et al. (1982) described a coping style called ‘hardiness’,
• has three components: control, commitment and challenge.
Low control suggests a tendency to show feelings of helplessness in the face of stress.
Commitment is defined as the opposite of alienation: individuals high in commitment find meaning in their work, values and personal relationships.
Individuals high in challenge regard potentially stressful events as a challenge to be met with expected success.
• Hardiness may be protective in developing cancer.
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emotional responses to cancer
• Up to 20% of cancer patients may show
severe depression,
grief,
lack of control,
personality change,
anger and anxiety.
• Persistent deterioration in mood does seem to be related to previous psychiatric history, lack of social support, age, and lack of an intimate relationship.
• In sufferers with advanced cancer, psychological morbidity was related to functional status (how well the patient functioned physically) and suggested that lowered functional status was associated with higher levels of depression, which was also related to lower social class.
• Women with breast cancer often report changes in their sense of femininity, attractiveness and body image. (shown to be greater in women who have radical mastectomies rather than lumpectomies)
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cognitive responses to cancer
• A ‘fighting spirit’ is negatively correlated with anxiety and depression while ‘fatalism’, ‘helplessness’ and ‘anxious preoccupation’ are related to lowered mood
• Taylor (1983) examined the cognitive adaptation of 78 women with breast cancer. She reported that these women responded to their cancer in three ways.
First, they made a search for meaning (understand why they developed cancer). Meanings that were reported included stress, hereditary factors, ingested carcinogens such as birth control pills, environmental carcinogens such as chemical waste, diet, and a blow to the breast.
Second, they also attempted to gain a sense of mastery by believing that they could control their cancer and any relapses.
- Such attempts at control included meditation, positive thinking, and a belief that the original cause is no longer in effect.
Third, the women began a process of self-enhancement.
- This involved social comparison, whereby the women tended to analyse their condition in terms of others they knew.
• The women showed ‘downward comparison’, which involved comparing themselves to others worse off, thus improving their beliefs about their own situation.
• According to Taylor’s theory of cognitive adaptation, the combination of meaning, mastery and self-enhancement creates illusions which are a central component of attempts to cope.
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psychology and alleviating symptoms
* Experiences of cancer sufferers, which included very distressing pain, breathing difficulties, vomiting, sleeplessness, loss of bowel and bladder control, loss of appetite, and mental confusion.
* Psychosocial interventions have therefore been used to attempt to alleviate some of the symptoms of the cancer sufferer and to improve their quality of life:
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pain managment
• Biofeedback and hypnosis have been shown to decrease pain.
• Turk and Rennert (1981)
- encouraged patients with cancer to describe and monitor their pain,
- encouraged them to develop coping skills,
- taught them relaxation skills,
- encouraged them to do positive imagery and to focus on other things.
They reported that these techniques were successful in reducing the pain experience
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social support
• Support groups: emphasize control and meaningful activities and aim to reduce denial and promote hope.
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treating nausea
* Cancer patients are often offered chemotherapy as a treatment for their cancer, which can cause anticipatory nausea, vomiting and anxiety.
* Respondent conditioning and visual imagery, relaxation, hypnosis and desensitization have been shown to decrease nausea and anxiety in cancer patients.
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body image counselling
• The quality of life of cancer patients may also be improved through altered body image counselling, particularly following the loss of a breast and, more generally, in dealing with the grief at loss of various parts of the body
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cognitive adaptation strategies
* Taylor (1983) used such strategies to improve patients’ self-worth, their ability to be close to others, and improvement in the meaningfulness of their lives.
* Such methods involve self transcendence and this has been related to improvement in well-being and decrease in illness-related distresses.
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the work of the simontons
• Simonton and Simonton (1975) are applied psychosocial factors and interventions to improve patients’ quality of life using a whole-person approach.
• This involves the following processes:
a. Relaxation (decreases muscle tension and therefore decrease pain)
b. Mental imagery, whereby cancer patients are encouraged to focus on something positive (this aims to develop a belief in the ability to recover, therefore decreasing pain, tension and fear)
c. Exercise programmes, which aim to increase the sense of well-being.
• These methods are also currently being used at Penny Brohn Cancer Care in the UK.
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voluntary euthanasia
* Euthanasia carried out by A at the request of B.
* There is a close connection between voluntary euthanasia and assisted suicide, where one person will assist another to end her life - for example, when A obtains the drugs that will allow B to suicide.
* Euthanasia can be voluntary even if the person is no longer competent to assert her wish to die when her life is ended.
* You might wish to have your life ended should you ever find yourself in a situation where, whilst suffering from a distressing and incurable condition, illness or accident have robbed you of all your rational faculties, and you are no longer able to decide between life and death.
* If, whilst still competent, you expressed the considered wish to die when in a situation such as this, then the person who ends your life in the appropriate circumstances acts upon your request and performs an act of voluntary euthanasia
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non voluntary euthanasia
• When the person whose life is ended cannot choose between life and death for herself - for example, because she is a hopelessly ill or handicapped newborn infant, or because illness or accident have rendered a formerly competent person permanently incompetent, without that person having previously indicated whether she would or would not like euthanasia under certain circumstances
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involuntary euthanasia
* When it is performed on a person who would have been able to give or withhold consent to her own death, but has not given consent - either because she was not asked, or because she was asked but withheld consent, wanting to go on living.
* Whilst clear cases of involuntary euthanasia would be relatively rare (for example, where A shoots B without B's consent, to save her from falling into the hands of a sadistic torturer), it has been argued that some widely-accepted medical practices (such as the administration of increasingly large doses of pain killing drugs that will eventually cause the patient's death, or the unconsented-to withholding of life-sustaining treatment) amount to involuntary euthanasia.
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palliative care
• Illness affects all parts of a patient’s life (and their families)
• Considering the patient holistically can improve their overall care
• The multi-disciplinary team is your friend! Other people have expertise that can help the patient, they may find out bits of information that can help you.
• Palliative care is an example of holistic multidisciplinary care, but the principles apply to all areas of clinical practice.
• Palliative care: “... an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.” [WHO]
• Palliative Care:
concept of care, not place of care
quality rather than quantity
affirmation of death as a natural part of life
neither hastens nor postpones death
holistic care – physical, emotional, social & spiritual
respect, empowerment, choice, compassion
team approach to care
enhances quality of life
applicable from diagnosis to death & into bereavement
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what does palliative care involve
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careful & continual assessment of symptoms
concept of “total pain”
the family as the unit of care
active total care
listening
questioning
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“You matter to the last moment of your life and we will do all that we can, not only to help you die peacefully, but to live until you die.”
• Essence into Practice:
life-limiting illness (cancer/ non-malignant disease)
support system to help patients “live until they die”
support system to help families & carers cope during the illness & into bereavement
• Who gets Palliative Care?
Traditionally aimed at patients with incurable cancer
More recently (past years) patients with any lifelimiting diagnosis
BUT
Is it fair to wait until an illness is incurable/life-limiting before trying to improve their quality of life?
Principles of palliative care (i.e. holistic care) applicable to all and should be part of everyday practice Most palliative care is carried out by non-specialists
