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Acute Phase Response

Pro-inflammatory cytokines  TNF-a/b, IL-1a/b, IL-6, IFN-ay, IL-8

Anti-inflammatory cytokines  TNF-a binding protein

 IL-1 binding protein
Bacterial infections  Strong systemic acute phase response
  CRP

Viral infections  Milder systemic acute phase response

Nerve Fibres

Mechanoreceptors in skin  A-beta

Fast conducting pain  A-delta

Slow conducting pain  C-fibre (unmyelinated)

Intrafusal fibres  1A afferent sensory

 Gamma motor neurones motor

Lower motor neurones (extrafusal muscle fibres)  A-alpha motor neurones

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Tumour Formation and Growth

Oncogenes  Alteration of key genes controlling the growth

of cells
 Ignores signals of cell apoptosis – continuous
cell formation

Degrees of differentiation of malignant cells  Well differentiated malignant neoplasm

 Poorly differentiated malignant neoplasm
 Anaplastic malignant neoplasm
o Immature cells which have little
differentiation at all

Dukes’ staging  Used for colorectal carcinomas

Systemic systems caused by neoplasm  Weight loss

 Loss of appetite (anorexia)
 Fever
 General malaise
 Anaemia

Fast growing cells  High cell turnover

 Both proliferation and apoptosis rates are high

Skin tumours

Skin tumours  Basal cell carcinoma

o Local
 Squamous cell carcinoma
o May metastaise

 Malignant melanoma
o Consequence of excessive exposure to
UV light
o Present with asymmetrical borders and
variable pigmentation

Breslow thickness  Measured thickness on histological section of a

malignant melanoma

Kaposi’s sarcoma  Tumour of vascular origin

Herpes simplex virus and shingles  May become latent within a DRG
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Breast tumours

Breast cancer  Most common cancer in the UK

 Most breast tumours are invasive
adenocarcinomas
o 53% ductal pure

 Presents in 4 main ways

o Palpable lump
o Abnormalities detected on
mammography
o Incidental histological findings
o First manifestation of metastatic
disease

Metastatic spread  Breast cancer can spread directly or

metastasise to the pleura

Respiratory tract disease + tumours

Tuberculosis  Patients taking anti-inflammatory (e.g.

rheumatoid arthritis) which effect the
inflammatory cascade are at risk of old
infections with tuberculosis
 Primary tuberculosis is usually mild and often
asymptomatic
o 90% of cases does not proceed further
 Remaining 10% develop clinical disease
 The infection can spread to lungs and other
organs, and may invade the circulation
causing widespread disease

Common problems with bronchial adenocarcinoma  Most common cause of death (lung cancer)

 Cough
 Haemoptysis
 Breathlessness, stridor or wheeze
 Chest infections

 Lethargy
 Anorexia and weight loss
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GI tract tumours

Oesophageal carcinoma  Malignant tumours are much more common

than benign
 Most common in the lower third
 Cigarette smoking, high alcohol intake,
environmental carcinogens, hot drinks and
human papilloma virus

 50/50 squamous cells and adenocarcinoma

 Incidence of adenocarcinoma is probably due
to the increasing incidence of Barrett’s
oesophagus

Gastric and small intestine adenomas  Usually asymptomatic until advanced

 Non-specific symptoms such as weight loss,
abdominal pain, anorexia, vomiting and altered
bowel habits

Gastric tumours spread  Direct invasion

 Lymphatic spread
 Spread via bloodstream
 Trans coelomic spread

Carcinoma of the colon  Second most common cause of death, after

bronchial carcinoma
 Nearly always an adenocarcinoma
o Most common in rectum
o Then sigmoid, then ascending colon

 Peak incidence is between 60-79 yrs

 May be asymptomatic, but may cause occult
bleeding and anaemia

Dukes’ staging  Colorectal carcinomas

Liver and pancreatic cancer

Liver cancer  Closely associated with Hepatitis C

Pancreatic cancer  One of the highest mortality rates of any

cancer
 Occur mainly in 60-80 yrs
 60% arise in the head, 15% in the body and 5%
in the tail
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Female reproductive tract tumours

Ovarian cancer  80% of ovarian tumours are benign

 Oocytes  Occur in women 20-45 yrs

 Malignant tumours are more common in

women 40-65 yrs

 Account for a disproportionate number of

deaths as many ovarian cancers are not
detected early in their development

 Complaints of pelvic and abdominal pain,

increased abdominal size/persistent bloating,
loss of appetite and feeling full quickly
 Increased urinary symptoms, change in bowel
habits, postmenopausal bleeding, rectal
bleeding, back pain and extreme fatigue

Endometriosis  Affects 10% of women between 30-40 yrs

 Menstrual irregularities are common

 Patients present with severe dysmenorrhoea,
dyspareunia and pelvic pain due to peri-uterine
adhesions and intrapelvic bleeding

 Can lead to infertility

Uterine cancer  Carcinoma of the endometrium is the most

common invasive cancer of the female genital
tract

Fibroids  Leiomyomas as the most common benign

tumours of the uterus
 Affect over half of all women over 30 yrs

Cervical cancer  Linked to Human Papilloma Virus (HPV)

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Male urogenital tract tumours

Testicular cancer  Most common in 15-34 yrs

 Presents with testicular mass which is often
painful

Renal tumours  Both benign and malignant tumours are found

Bladder cancer  More common in men than women (3:1)

 Occurs in patients between 50-80 yrs
 90% of bladder tumours drive from transitional
epithelium

Prostate cancer  Develops in men over 50 yrs and incidence

increase with age (90% of men aged 70yrs)
 Develops in the peripheral zone

 Spread is by direct invasion, via bloodstream

and lymphatic drainage

 PSA antigen detection in diagnosis and

management of prostate cancer

Gleason staging  Used for prostate cancer to score the gland and
the degree of tumour cell differentiation
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Renal Pathology

Renal pathology  Recognised by changes in the urine or blood

Three main causes of pathological conditions  Reduced blood through kidneys

 Damage to the glomerular basement
membrane
 Obstruction of outflow

Disruption of the glomerular basement membrane
(GBM)
 Make it leaky for plasma proteins to escape
 Loss of plasma proteins will alter the normal
oncotic mechanisms at the capillary beds
 Causes widespread oedema as interstitial fluid
remain and accumulates as it is not drawn back
into the circulation (due to lack of plasma
proteins)

Nephrotic syndrome  Proteinuria – frothing urine

 Hypoalbuminemia – excreted in the urine
 Generalised oedema – water stays in interstitial
space
 Hyperlipidaemia and lipiduria

Nephritic syndrome  Haematuria – blood in urine

 Oliguria – less than normal amount of urine
 Oedema
 Hypertension – renin release, increase in BP

Acute renal failure  Pre-renal

o Blood supply to the kidney
 Renal
o Kidney itself
 Post-renal
o Obstruction of urinary flow
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Pathology of the CNS

Increased intracranial pressure  Fastest onset would be caused by an arterial

aneurysm bursting
 Extradural and intracerebral haemorrhage will
also raise the ICP and cause drowsiness and
coma
 Subdural haemorrhage will raise the pressure
slower, similar to tumours (both are space
occupying lesions)
Cerebellar tonsils  If suffering from a space occupying lesion:
 Drainage of CSF at the lumbar cistern would
allow the brain to move caudally very
suddenly, making the cerebellar tonsils to
become pressed against the edges of the
foramen magnum and be compressed
o Will compress the respiratory centres

Brain tumours

Glial cells  Overarching name for oligodendrocytes,

astrocytes and ependyma

Oligodendrogliomas  Most common in 40-50 yrs

Ependymomas  Tumour in the walls of the fourth ventricle

 May project into the fourth ventricle and cause
a secondary hydrocephalus
o Excess CSF build up in the ventricles and
may increase pressure within the head

Choroid plexus neoplastic change  Forming papilloma

 In children, these are most common in the
lateral ventricles
 In adults, these are most common in the fourth
ventricles
 As these tumours enlarges, it may obstruct CSF
flow and cause hydrocephalus

Colloid cyst  Non-neoplastic lesion of the ventricular system

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of the third ventricle
 Positional headache

Medullablastomas  Occur mainly in children and exclusively in the

cerebellum
 May lead to hydrocephalus
 Highly malignant and can spread through the
CSF

Pituitary tumours (adenomas)  Diagnosis is made on endocrine changes

and/or visual changes

Meningiomas  Uncommon in children

 Usually slow growing and present with vague
non-localising symptoms

Metastatic brain tumours  Deriving from a primary tumour

 80% of brain metastases arise from the lung,
breast, skin (melanoma), kidney and GI tract

PNS tumours, meningitis and CNS infections

Schwannoma  Growing on the vestibular branch of CN VIII,

termed an acoustic neuroma
 Patients present with tinnitus, hearing loss and
vertigo

Bacterial meningitis  Severe, but less common than viral

 Affects children and adolescents featuring
acute onset skin rashes

Viral meningitis  Milder disease presenting with headache,

fever, photophobia, but less neck stiffness
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Blood Pathology
Red Blood Cells
Haematocrit (HCT) or Packet Cell Volume (PVC)
Mean Cell Haemoglobin (MCH) or (MCHC)
 Colour of RBCs
Normocytic anaemia
 Normal size, but too few RBCs
Mean Cell Volume (MCV)
 Size of RBCs
Erythrocyte Sedimentation Rate (ESR)
 Test how quickly erythrocytes settle at the
bottom of a blood sample test tube
o Normally relatively slow (<20mm/hr)
 Non-specific evidence for disease
Platelets
Thrombocytopenia
 Deficits of megakaryocytes
Essential Thrombocythemia
 Deficits of megakaryocytes
Year 2 205
 The ratio of the volume of red blood cells to
the total volume of blood
 Men have higher %RBC than women
 Abnormal low HCT – Anaemia
 Abnormal high HCT – Polycythaemia
 MCH below 27pg  Hypochromia (from iron
deficiency)
 E.g. blood loss due to injury
 MCV less than 80fl  Microcytic anaemia
(lower than normal size)
 MCV more than 95fl  Megaloblastic anaemia
(deficiency of B12 vitamin)
 Measure of concentrations of proteins in
plasma
 A faster-than-normal rate may indicate
inflammation of the body
 Too few platelets
 Abnormal bleeding such as
o Spontaneous skin purpura (burst of
small blood vessels)
o Mucosal haemorrhage
o Prolonged bleeding after trauma
 Rise in platelet, abnormal development
 Spontaneous bruising often occurs
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Anaemia

Iron deficiency = micro, too small cells

Low MCHC  Hypochromia anaemia

Low MCV  Microcytic anaemia

Symptoms  Gradual onset of lethargy, weakness, dizziness

and palpitations

B12 deficiency = macro, too large cells

- Common in terminal ileum disease (common in Crohn’s disease)

High MCV  Macrocytic anaemia

High MCV  Megaloblastic anaemia

Low platelets  Thrombocytopenia

High platelets  Essential thrombocythemia

White Blood Cells

 Whereas the number of RBCs remain fairly constant, the number of white blood cells will vary
according how a person interacts with their environment

Bacterial infection  Neutrophils (Macrophages inside tissue)

Viral infection  Lymphocytes

Parasitic infection  Eosinophils

Allergy (infection)  Basophils (Mast cells inside tissue)

 Eosinophils

Chronic leukaemia  B-cell proliferation

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 Uncontrolled infections

Myeloma  Malignant proliferation of plasma cells in the

bone marrow

Leukaemia

Acute lymphoblastic leukaemia  Most common in children under 14 yrs

- Most common in kids  Rarely affects young adults

Acute myeloid leukaemia  Most common in adult and elderly

- Most common in adults and elderly  Do also occur in children and young adults

Chronic myeloid leukaemia  Most common in adults around 60-65 yrs

- Most common in adults

Chronic lymphoblastic leukaemia  Second most common in adults over 50 yrs

- Second most common in adults  Predominantly in elderly
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Gut Pathology

Oesophagus Barret’s oesophagus – metaplastic change of lower oesophagus epithelium

Causes
 Related to GORD, and also smoking and alcohol

Mechanism
 Gastric reflux can lead to metaplastic change of the oesophageal mucosa in the
lower oesophagus

Stomach Gastritis – inflammation of the stomach lining

Causes
 Bacterial infection, NSAIDs, alcohol, reflux of the duodenal contents (pyloric
sphincter)
 Defective parietal cells

Mechanisms
 Different agents (such as bacterial) which may irritate the gastric mucosa and
develop inflammation

Peptic ulcer – local area of mucosal damage

Causes
 70% of gastric ulceration is from helicobacter pylori
 Also produced by the action of gastric secretions (e.g  gastric acid)

Mechanism
 Local damage to gastric mucosa and inflammation
 If the agent persists, the damage continues in repairing tissue
 It may perforate the gut wall, or heal completely if the agent is removed

Clinical features
 Epigastric tenderness may be present
 Pain may wake patient up between 2 – 4 at night
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 Some people get referred pain in their back between T6-T9
 May result in haematemesis (vomiting blood)

Small intestine Peptic ulcer (duodenum) – same as in the stomach

Causes
 90% of duodenal ulceration is from helicobacter pylori

Coeliac disease – allergic reaction to gluten

Causes
 Auto-immune response which causes damage to the tight junction joining the
enterocytes
 A type of T cell is activated by gluten which damage the epithelial enterocytes

Clinical features
 Often diagnosed in patients found to be iron or folate deficient
 Malaise, fatigue, diarrhoea and weight loss is common

Large intestine Diverticular disease

(colon)
Causes
 As people get older, the intracolonic pressure promotes the development of
herniations ‘diverticulum’ of the mucosa and submucosa along the vascular entry
points of the colon which are ‘weakened’

Mechanisms
 Can occur along the whole colon, but is common near the sigmoid and rectum
 Diverticulosis: development of multiple asymptomatic diverticuli
 Diverticulitis: inflammation and healing response of a diverticulum
 Diverticular disease: includes haemorrhage into a diverticulum, inflammation of a
diverticulum and eventual rupture of the colonic wall at the site of a diverticulum

Prevalence of diverticulosis
 Increases with age
 Prevalence is 60% after 85 yrs
 Condition of Marfan’s and Erlhers Danlos syndrome as it is associated with aging
and replacement of collagen

Clinical findings
 Lower abdominal pain (depending on the site), fever and leucocytosis
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Inflammatory Crohn’s disease Ulcerative colitis

bowel disease Any part of the bowel can be affected, Only colon. Starts in rectum and may
but common in terminal ileum spread to all colon

Causes Causes
 Evidence suggests that it is  May be similar to Crohn’s
environmental, possible
immunological origin Mechanisms
 Inflammation is limited to the mucosa
Mechanisms  Oedema of mucosa and submucosa
 Inflammation in all layers  Depletion of goblet cells
 Swelling of the mucosa and
submucosa due to severe Clinical features
submucosal oedema – loss of folds in  Patients present with mild fever,
the gut malaise, loss of appetite and
 Small superficial areas of malabsorption: diarrhoea is usual
haemorrhagic ulceration develop  May have changes to their nails
which deepen to form fissures (clubbing, leukonychia and
koilonychia)
Clinical features
 Patients present with mild fever,
malaise, loss of appetite and
malabsorption: diarrhoea is usual
 May have changes to their nails
(clubbing, leukonychia and
koilonychia)

Complications
 Risk of malabsorption
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Pancreas Pancreatitis – inflammatory condition of the pancreas resulting in necrosis of both

exocrine (acinar cells) and endocrine (islet of Langerhans) cells

Causes
 Alcohol abuse, occlusion of the bile duct by gallstones
 More frequent in men with a peak incidence between 35-45 yrs

Acute pancreatitis
 Sudden onset of abdominal pain which radiates to the thoracolumbar region –
usually resolves within 48 hours – pain is thought to be caused by rise in
pancreatic ductal pressure

Chronic pancreatitis
 Same process as with acute, but with further acinar and islet cell loss, infiltration
of the gland with inflammatory cells and irregular deposition of collagen

 Loss of production of pancreatic enzymes results in less ability to digest food

sufficiently for absorption, which may lead to malabsorption and weight loss
 Loss of lipase affects intestinal fat absorption and leads to steatorrhea

Liver and gall Jaundice – skin and sclera of the eye turns yellow due to binding of bilirubin in the
bladder tissues

Causes
 Gallstones
 Alcoholic liver disease
 Pancreatitis
 Hepatitis

Mechanism
 Extensive haemolysis (destruction) of RBCs may produce excessive levels of
unconjugated bilirubin
 Damaged or necrotic hepatocytes (liver) are unable to metabolise unconjugated
bilirubin which then accumulates and escape into the blood
o Hepatocytes may be damaged by infection, drugs and alcohol

 Circulation bilirubin binds to tissues and make it yellow

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o Both conjugated and unconjugated bilirubin cause jaundice

Gall stones – crystalized cholesterol forming ‘stones’ in the bile duct

 Usually asymptomatic, only cause symptoms (often related to eating high fat
foods) if they obstruct the gall bladder neck, or become lodged in the ducts
 Pain is initially in the epigastrium or right upper quadrant with referral to the right
shoulder

Cirrhosis – chronic alcoholic liver disease the most common

Causes
 Chronic alcohol:
o 80% of cases are associated with alcohol abuse
 Non-Alcoholic Fatty Liver disease (NAFLD)
o Similar effects, but due to the level of sugar and fructose in the diet

Ascites – increased fluid in the peritoneal cavity

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