Clincial Conditions Flashcards
What are the markers used to identify excessive alcohol intake? What are the results
GGT- liver enzyme that is increased by heavy alcohol intake
MCV- increased by prolonged heavy drinking
ALT and AST- increased levels indicate liver damage
What is the presentation of Hep B? (10)
Fatigue General aches and pains High temp (38+) Nausea and vomiting Decreased appetite Abdominal pain Diarrhoea Jaundice Dark urine Pale-grey faeces
What are the diagnostic markers for acute Hep B?
Positive for:
HBsAg
IgM HBcAb
Negative for:
HBsAb (not protected against it)
What are the diagnostic markers for chronic hep B?
Positive for:
HBsAg
IgG HBcAb
Negative for:
HBsAb (not mounted a sufficient immune response)
What two enzymes would you measure to diagnose acute pancreatitis? What would be the results?
Serum amylase: increase
Serum lipase: increase
What is hereditary haemochromatosis?
A condition in which iron levels in the body slowly build up of the years
What are the earlier symptoms seen with hereditary haemochromatosis? (5)
Fatigue, Weight loss Weakness Joint pain Men: erectile dysfunction Women: irregular or absent periods
What are the later symptoms of hereditary haemochromatosis?
Loss of libido and smaller testicles Abdominal pain and swelling Chest pain Darkening of skin/jaundice Severe pain and stiffness in joints Swelling of hands and feets Shortness of breathe Arrhythmias
What are the complications of hereditary haemochromatosis?
Liver damage
Diabetes (damage to pancreas)
Heart failure (damage to cardiac muscle)
Arthritis (damage to joints)
What is the current treatment for hereditary haemochromatosis?
Phlebotomy (removing some blood) Chelation therapy (giving medication that causes iron to be excreted in urine and faeces)-done if phlebotomy is not an option
What is alpha-1 antitrypsin deficiency?
Deficiency in the AAT protein which controls enzymes that would otherwise damage healthy lung tissues
What is the pathophysiology of an alpha1 antitrypsin deficiency?
Caused by mutations to the SEPRINA1 gene, causing altered configuration of molecules, preventing their release
This results in the uncontrolled action of proteases (ie neutrophil elastase) which damage alveoli walls and can cause emphysema
What is the presentation of an alpha 1 antitrypsin deficiency?
Dyspnea (shortness of breathe)
Cough
Sputum production
Wheezing
What are the complications of an alpha 1 antitrypsin deficiency?
Same as with COPD: Pneumothorax Pneumonia Acute exacerbation of air flow obstruction Respiratory failure
What is a coal-workers pneumoconiosis?
An industrial disease that is the result from breathing in carbon dust over a period of years. It can lead to inflammation, fibrosis and necrosis
Describe the symptoms associated with both simple and complicated coal-workers pneumoconiosis
Simple: shortness of breath (dyspnea) and chronic cough
Complicated: dyspnea, chronic cough and black sputum
What are the complications of coal-workers pneumoconiosis?
Lung dysfunction, pulmonary hypertension and heart problems
What is the difference betweenlobar pneumonia and bronchopneumonia?
LP: whole lobe affected
BP: only bronchioles and adjacent alveoli affected
What are commonest causative organisms of lobar pneumonia?
Strep. Pneumoniae
Haemophilus influenzae
Klebsiella pneumoniae
What are the complications of lobar pneumonia? (3)
Pleurisy (pleura become inflamed-can lead to resp failure)
Lung abscess (rare, usually seen in those with pre-existing illness or history of severe alcohol misuse)
Sepsis
What is the microscopic appearance of acute appendicitis? (Think about structure and cells present)
Structure:
No villi
No crypts
Ulcerated, complete loss of epithelium
Cells:
Polymorphs- neutrophils (most abundance acute inflammation cell)
*the epithelium is destroyed and replaces by inflammatory tissue that released proteases
What are the macroscopic features of acute pancreatitis?
Oedema due to fluid exudate
Swollen due to pus accumulation forming an abscess- fibrin mesh covering it
What type of necrosis occurs in the appendix?
Coagulative
What are the possible causes of acute pancreatitis?
Blockage to entrance of appendix by:
- Faecal matter
- Swollen lymph node (in wall of bowel due to infection elsewhere-upper resp tract)
These obstructions lead to inflammation and swelling, pressure can then cause the appendix to burst
What are the complications of an acute appendicitis? (2)
Peritonitis
Abscesses
What are the macroscopic features of bacterial meningitis?
Swelling,
Sulci filled with pus (giving cloudy appearance)
Gyri and sulci indistinguishable
What are microscopic features of bacterial meningitis?
Pus build up- made from neutrophils
It accumulates adjacent to the brain
What are commonest causative organisms of bacterial meningitis? (3)
Meningococcal bacteria
Pneumococcal bacteria
Haemophilus influenzae type B (Hib)
What are the complications of bacterial meningitis? (6)
Hearing and vision loss
Epilepsy
Problems with memory, concentration, co-ordination, movement and balance
Amputation and bone/joint problems (arthritis)
Kidney problems
What are the complications of gall stones? (5)
Acute cholecystitis (inflammation of gallbladder)
Jaundice
Acute cholangitis (infection of bile ducts)
Acute pancreatitis
Gallbladder cancer
What is ascending cholangitis?
Inflammation of the bile duct
What is the link between ascending cholangitis and gallstones?
Cholangitis is caused by a bacterial infection as a result of an obstruction of the biliary tree. A gall stone is the most common cause of the obstruction
What are the common causative organisms of ascending cholangitis? (3)
E.coli
Klebsiella species
Enterococcus species
What are the complication of acute cholangitis? (3)
Acute pancreatitis
Inadequate biliary drainage due to endoscopy, radiology or surgery
Hepatic abscesses
What is hereditary angio-oedema?
Autosomal dominant inherited blood disorder causing episodic attacks of swelling which can affect the following: Face Extremities Genitals GI tract Upper airways
What is the presentation of hereditary angio-oedema?
Recurrent swelling in face, extremities, GI, lips, larynx
Sensation of fullness but not pain or itching
*those who experiment abdominal swellings may experience acute pain in abdomen
What is chronic granulomatous disease?
A primary immunodeficiency disorder of phagocytes resulting from impaired killing of bacteria and fungi
What is the presentation of chronic granulomatous disease?
Early onset (first 2 years of life)
Severe recurrent bacterial and fungal infections
Dysregulated inflammatory response resulting in granuloma formation and other inflammatory disorders like colitis
Short stature
What is the presentation of rheumatoid arthritis?
Throbbing and aching pain in joints (often worse in the mornings and after periods of activity)
Stiffness in joints (lasting longer than 30 minutes-this would indicate osteoarthritis)
Swelling warmth and redness of joints
What are the microscopic features of rheumatoid arthritis?
[chronic inflammatory features:]
Pannus (layer of granulation tissue), Hyperplasia, fibrosis, errotion of articular cartilage, lymphocytes
What is a rheumatoid nodule?
A lump that appears subcutaneously in some patients with RA, usually not tender but occasionally painful
What is microscopic appearance of a rheumatoid nodule?
centre of fibrinoid necrosis
cellular palisade which is densely packed layer of macrophages and fibroblasts
Fibrous shell containing T cells and plasma cells in association with blood vessels
(Paler patchy middle, purple outline, then pink circle around that)
What is the presentation of ulcerative colitis?
Recurring diarrhoea which may contain blood, pus or mucus
Abdominal pain
Frequent need to empty bowels
Fatigue, loss of appetite and weight loss
What is the macroscopic appearance of ulcerative colitis?
Lumps (psuedopolyps)
Ulceration
Redness
Distal colon
What are the microscopic features of ulcerative colitis?
Crypt distortion (loss of organisation) Fibrosis (due to chronic inflammation) Ulceration Limited to mucosa and submucosa Crypt abscesses
What are the complications of ulcerative colitis?
Osteroporisis (due to corticosteroid medication)
Poor growth and development (lack of absorption)
Primary sclerosing cholangitis
Toxic megacolon (dilated colon and other issues)
What is the presentation of Crohn’s disease?
Diarrhoea possibly containing blood and mucus
Abdominal pain
Fatigue and weight loss
What are the macroscopic features of Crohn’s disease?
Cobblestone appearance Thickening of wall Thinning of lumen Bowel fistulae Discontinuous distribution (but can be found throughout GI tract) Anal lesions
What are the microscopic features of Crohn’s disease?
Granulomas
(Sometimes) cyrpt abscesses
What are the complications of Crohn’s disease? (2)
Intestinal strictures (narrowing that causes problems by slowing or blocking the movement of food through an area) Fistulas
What are the macroscopic features of chronic cholecystitis?
Thick walls-opaque grey/white appearance
Scarring (fibrosis)
Perforation of wall
Fistula formation
What is chronic cholecystitis?
repeated attacks of acute inflammation on the gallbladder, usually due to gallstones. The gallstones may block the opening of the gallbladder into the cystic duct or block the cystic duct itself.
What are the microscopic features of chronic cholecystitis?
Thickening of the gallbladder wall - due to fibrosis/muscular hypertrophy - key feature.
Chronic inflammatory cells - usu. “minimal”.
Lymphocytes - most common.
Rokitansky-Aschoff sinuses - common.[3]
Entrapped epithelial crypts – pockets of epithelium in the wall of the gallbladder.
+/-Foamy macrophages in the lamina propria (cholesterolosis of the gallbladder).
What is the role of helicobacter pylori in chronic gastric?
It is a gram negative bacilli that colonise and infect the stomach
Survive in mucous layer (covering gastric epithelium)
Can cause intense inflammatory responses in stomach and is associated with tissue damage
What changes can be seen microscopically in chronic gastritis caused by H.pylori?
Helicobacter pylori organisms. Chronic inflammation (and some acute inflammation) in the lamina propria and superficial epithelium. Lamina propria fibrosis. Mucosal atrophy. Intestinal metaplasia.
How does helicobacter pylori cause gastritis?
By stimulating production of pro-inflammatory cytokines and by directly injuring epithelial cells and increasing acid secretion.
What are the complications of H.pylori associated chronic gastritis?
Stomach ulcers
Polyps in stomach
Tumours in the stomach (benign and malignant): Gastric adenocarcinoma or MALT (mucosa associated lymphoid tissue) lymphoma.
What is cirrhosis? What is process of this?
Scarring of the liver caused by continuous long term liver damage
Scar tissue replaces healthy tissue and prevents the liver working properly
What are some causes of liver cirrhosis? (3)
Alcohol consumption
Hepatitis
Non-alcoholic steatohepatitis (NASH)
What are some complications of cirrhosis? (4)
Swollen varices Ascites and peripheral oedema Encephalopathy (disease affecting the function of the brain) Sever bleeding (due to livers decreased ability to clot blood)
What is the macroscopic appearance of a cirrhotic liver?
Shrunken
Yellow-ish tan colour
(May be enlarged if alcohol was the cause)
Bumpy effect- micro/macronodular
What is the microscopic appearance of a cirrhotic liver?
Scar tissue replacing normal parenchyma Dilated sinusoids No bile duct(?) Fibrous septa Fatty cells Necrosis
What is the pathophysiology of Tuberculosis?
Infection with mycobacterium tuberculosis due to exposed of lungs/mucous membranes to infected aerosols
TB develops in the lungs for 2-12 weeks until there is a sufficient number of organisms to illicit an immune response
(Produces no toxins, causes disease by persistence and induction of cell mediated immunity)
What is the microscopic appearance of TB? (4)
Granulomas made of: Giant cells (langhans type) Caseous necrosis centre Lymphocytes Epithelioid macrophages
How does TB differ to sarcoidosis?
TB has caseating granulomas (necrotic centres) whereas Sarcoidosis has non-caseating epithelioid cell granuloma
What is the presentation of sarcoidosis? (3)
Shortness of breath
Persistent dry cough
Tender red bumps or patches on the skin (shins) as well as rashes on upper body
What is the microscopic appearance of sarcoidosis?
Granulomas: Non-caseating Giant cells Involves lymph nodes, lungs Lymphocytes
What causes scurvy?
Lack of Vit C
What is the pathophysiology of scurvy?
Without vitamin C, collagen cannot be replaced, the body’s tissues will begin to breakdown and deteriorate
What is the presentation of scurvy?
Fatigue Irritability Pain in limbs (legs) + severe joint pain Small red-blue dots on skin Swollen gums Shortness of breath Easy bruising + redness and swelling in recently healed wounds In infants: lack of appetite, irritability, poor weight gain, diarrhoea, temp >38
What is Ehlers-Danlos syndrome?
A group of rare inherited conditions that affect connective tissue
What is the clinical manifestation of Ehlers-Danlos syndrome?
Joint hyper-mobility
Stretchy skin
Fragile skin that breaks or bruises easy
What is osteogenesis imperfecta?
Brittle bone disease- genetic disorder that mainly affects the bones and results in the bones breaking easily
What is the clinical manifestation of Osteogenesis imperfecta?
Malformed bones and short, small stature Loose joints and muscle weakness Blue sclera hearing loss (age 20/30) Triangular face Curved spine Brittle teeth
What is alport syndrome?
A genetic disorder causing a defect in type IV collagen
What is the clinical manifestation of alport syndrome?
Kidney disease: haematuria, proteinuria
Hearing loss (due to abnormalities in ear)
Eye abnormalities due to misshapen lenses in the eyes
Abnormal coloration of the retina
Vision loss (as a result of previous 2 points)
What is the macroscopic appearance of a keloid scar?
Taller, more pronounced scar Smooth top Pink/purple in colour Irregular shape Grow beyond boundaries of original wound
*wont regress over time like a normal scar
What is the microscopic appearance of a keloid scar?
Type 3 (early) and type 1 (late) collage composition Lots of granulation tissue (scar tissue)
What is haemophilia A?
Deficiency in factor 8 affecting ones ability to clot
What is the presentation of haemophilia A?
Spontaneous haemorrhage
Easy bruising
Haemorrhage disproportionate to trauma
What are the results of a lab test if someone has haemophilia A? Consider the results of: Platelet count Bleeding time PT APTT Factor assays
PC: normal
BT:normal (measurement of platelet activity)
PT: normal (extrinsic pathway is fine)
APTT: prolonged APTT (factor 8 affecting intrinsic pathway)
Low factor 8 assay
What is haemophilia B? What is another name for it?
Christmas disease
Deficiency in factor 9, inherited conditions effecting ones ability to clot
What is the presentation of haemophilia B?
Spontaneous haemorrhage
Easy bruising
Haemorrhage disproportionate to trauma
What are the results of a lab test if someone has haemophilia B? Consider the results of: Platelet count Bleeding time PT APTT Factor assays
PC: normal BT: normal PT: normal (extrinsic pathway fine) APTT: prolonged (factor 9 is in this pathway) Low factor 9 assay
What is Von-Willebrand disease?
Most common inherited bleeding disorder which affects the blood’s ability to clot
Deficiency in Von-Willebrand factor
What is the function of Von-Willebrand factor?
Assists in platelet plug formation by attracting circulating platelets
It stabilises factor 8, protecting it from premature destruction
*a lack of this will cause inadequate platelet function and adhesion
What is the presentation of Von-Willebrand disease?
Bruising easily
Bleeding from gums, nose and lining of the gut
Prolonged bleeding after cuts, excessive bleeding after tooth extraction and surgery
Menorrhagia (heavy periods)
What are the results of a lab test if someone has Von-Willebrand disease? Consider the results of: Platelet count Bleeding time PT APTT
PC: normal
BT: increased (lowered platelet function)
PT: normal
APTT: prolonged (because Von-willebrand stabilises and protects factor 8 from destruction)
What is immune thrombocytopenic purpura?
Low platelet count with normal bone marrow
The low platelet count is due to reduced platelet survival
What is the presentation of thrombocytopenic purpura?
Purpuric rash
Increased tendency to bleed
What are the results of a lab test if someone has thrombocytopenic purpura? Consider the results of: Platelet count Bleeding time PT APTT
What other tests might you want to do?
PC: low
BT: prolonged (due to low platelet activity)
PT: normal (assesses clotting cascade not platelet function)
APTT: normal (assesses clotting cascade not platelet function)
Bone marrow biopsy may be necessary to exclude other causes of low platelet counts
What is a thrombophilia?
Inherited/acquired defect of haemostasis which results in a predisposition to thrombosis eg DVT/PE
Name some types of thrombophilia? (5)
Factor V leiden (no deactivation of factor V) Antithrombin deficiency (natural anticoagulant) Protein C deficiency (natural anticoagulant) Protein S deficiency (natural anticoagulant) Antiphospholipid syndrome (autoimmune- attacks phospholipids which keep blood at correct consistency)
What is the presentation of a thrombophilia resulting in DVTs?
Pain
Swelling
Tenderness and heavy ache in affected area (usually calve)
What is the presentation of a thrombophilia resulting in PEs?
Chest and upper back pain
Shortness of breath (dyspnea)
Feeling lightheaded and fainting
Coughing (usually dry but can cough up blood)
What is disseminated intravascular coagulation?
Thrombo-haemorrhagic disorder occuring as a secondary complication in a variety of conditions
(You bleed and clot at the same time)
What are some possible causes of DIC?
Sepsis (gram negative bacteria as these have endotoxins that activate clotting)
Severe trauma (especially in the brain where there is a larger amount of thromboplastin)
Extensive burns
Complication in childbirth (amniotic fluid embolism, retained dead foetus)
Malignancy
Snake bites
Severe transfusion reactions
What is the pathophysiology of DIC?
Systemic activation of blood coagulation leads to microthrombi
This consumes platelets and coagulation factors therefore activates fibrinolysis and patient experiences haemorrhages
How is DIC diagnosed?
Diagnosis is made by combining clinical presentation with lab abnormalities
Consider the following results of someone who has DIC?
Platelet count
FDP (fibrin degradation products) levels/D-dimer
Coagulation time
Peripheral smears (what do you see)
PC: low
FDP/D-dimer: increased (lots of fibrinolysis)
CT: prolonged (lack of clotting factors)
PS: see shistocytes (fragmented part of a RBC-typically irregularly in shaped, jagged, and have two pointed ends)
What is the treatment of DIC?
Treat underlying cause (antibiotics if sepsis etc)
Platelet transfusion if thrombocytopenic and bleeding or at risk of bleeding (surgery)
*occasionally you may need to administer an anticoagulant like Heparin
What is the role of thrombosis in MIs?
MI is caused by ischaemia often due to obstruction of a coronary artery by a thrombus
This occlusion starves the heart of oxygen and results in tissue death- infarction
What are the markers used to confirm and measure the severity of a MI?
Troponin mainly
But can use creatine kinase (this is used less as it can be released by damaged skeletal muscle also)
{*take measurements over a 24 hr period as levels may not immediately be raised}
What are the complications of MI?
Arrhythmias
Heart failure
Cardiogenic shock
Heart rupture
What is the pathophysiology of a DVT? [think about Virchows triad]
Formation of a thrombus (due to slow or turbulent blood flow, increased coagulability of blood, damage to epithelium of vein) within a Deep vein has the potential to embolise and cause issues around the body (ie PE). The thrombus itself may occlude/narrow the lumen causing further issues
Name some predisposing factors for DVT?
Anything that may disrupt Virchow’s triad
Changes in vascular wall [damage]: hypertension
Changes in blood flow [slow or turbulent]: sedentary life, being obese, major surgery/trauma
Changes in blood [hyper-coagulability]: DIC, old age, major surgery/trauma, pregnancy, oral contraceptives, thrombophilias (ie protein C deficiency)
Family history
Wha is the presentation of PE?
Chest and upper back pain described as sharp (may be worsen upon inhalation)
Dyspnea
Coughing (dry but can cough up blood)
Feeling lightheaded, dizzy, fainting
What is the pathophysiology of PE?
Usually arise from thrombi in deep veins of thigh and popliteal vein
Occlude/narrow lumens starving lungs-ischaemia- cell death
What are the risk factors for PE?
Blood clot in deep vein of lower limb
Previous PE
Anything that causes DVT:
Alteration in blood flow: immobilisation, injury, pregnancy, obesity, cancer
Damage to walls: surgery, catheter causing direct injury
Factors affecting coagulation: contraceptive pill, thrombophilias, pregnancy, obesity, cancer
What is the pathophysiology of an air embolism? When might it occur?
Occurs when one or more air bubbles enter a vein or artery and block it
This may occur during injections, surgical procedures, lung trauma and scuba diving
What is the presentation of a fat embolism?
Breathlessness and vague pains in the chest
Fever and tachycardia
Petechial rash
CNS symptoms from mild headache to significant cerebral dysfunction
Haematuria
What is the pathophysiology of an amniotic fluid embolism?
Amniotic fluid enters mother’s circulation through tear in membranes, this can cause sudden resp. Distress, hypotension, seizures, loss of consciousness, DIC-amniotic fluid contains prothrombotic substances
What is heterozygous familial hypercholesterolaemia?
A defect in LDL receptors which means there is decreased haptic uptake of LDLs therefore more circulating LDLs
What are the consequences of Heterozygous familial hypercholesterolaemia?
High levels of LDL cause an increased risk of atherosclerosis which can lead to ischaemic heart diseases and thus MI
What is the role of atherosclerosis in ischaemic heart disease?
Lipid deposits build up in the coronary arteries and become hardened, stiffened and swollen to form a plaque
This leads to limitation of blood flow causing the myocardial cells to be starved of oxygen
What is the role of atherosclerosis in transient ischaemia attack?
A dislodged atherosclerotic plaque in one of the carotid arteries can cause an embolus to occlude an artery in the brain
What is the pathophysiology of a transient ischaemic attack?
A temporary reduction of cerebral blood flow in a specific neurovascular distribution as a result of partial or total occlude- no permanent damage
What is the role of atherosclerosis in Cerebrovascular accident (stroke)?
A thrombus can form around an atherosclerotic plaque and break into an embolus and block a blood vessel in the brain
What is the pathophysiology of a stroke?
Vascular occlusion secondary to thromboembolic disease, ischaemia causes hypoxia and depletion of ATP so ionic gradients cannot be maintained and passive inflow of Na+, Ca2+ and water leads to cytotoxic oedema
What is the difference between an ischaemic stroke and a haemorrhagic stroke?
Ischaemic: obstruction within a blood vessel supply blood to the brain
Haemorrhagic: weakened blood vessels rupture (oftendue to uncontrolled hypertension)
What is the roles of atherosclerosis in bowel ischaemia?
Atherosclerosis can cause thrombosis and cause impaired blood transfusion to the intestine which delivers bacterial to an otherwise sterile location. This induces an inflammatory response
What is the role of atherosclerosis in peripheral vascular disease?
Atherosclerosis leads to blood vessels becoming narrowed and blood flow decreasing
Lacquers build up in the vessels and limit flow (and O2 delivery) to organs and limbs
Thrombi may develop and completely occlude artery which can lead to ischaemia- necrosis- loss of fingers, toes and limbs if untreated
What is presentation of peripheral vascular disease?
Intermittent claudication Hair loss on legs and feet Numbness/weakness in legs and muscle wasting Brittle, slow growing toenails Ulcers which don't heal Pale and shiny skins Erectile dysfunction Pain in both legs
What is the role of atherosclerosis in abdominal aortic aneurysm?
The walls of an AAA often carry an atherosclerotic burden, but atherosclerosis cannot be used to explain the initial defect and cause of the occlusion
What are the complications of an abdominal aortic aneurysm?
- Can leak and cause abdominal pain
- Rupture and cause death
- Associated with atherosclerosis and clot can embolise into smaller blood vessels
- (Rare) infection
What are the causes of Left ventricular hypertrophy?
Aerobic exercise and strength training
Increased afterload due to aortic stenosis, aortic insufficiency and hypertension
Hypertrophic cardiomyopathy
What are the complications of LV hypertrophy?
- Weakening of LV= heart failure
- Stiffening and loss of elasticity=heart failure
- Compression of coronary arteries= IHD
- Arrhythmias
- Aortic root dilation
- Stroke
- Sudden cardiac arrest
What is barrett’s oesophagus?
An abnormal change (metaplasia) in the cells of the lower portion of the oesophagus characterised by the replacement of stratified squamous epithelial cells by simple columnar epithelium cell with goblet cells
What causes Barrett’s oesophagus?
Gastroesophageal reflux (GERD) can cause it due to the exposure of oesophageal cells to stomach acid
What are the complications of Barrett’s oesophagus?
Oesophageal cancer (1/20 within 10-20 years)
What is traumatic myositis ossificans?
A benign process characterised by heterotrophic ossification within large muscles
What is the macroscopic appearance of benign prostatic hyperplasia?
Swollen gland
Narrowing of urethra
Smooth
Symmetrical glands
What are the complications of benign prostatic hyperplasia?
UTI
Acute urinary retention
What is the presentation of psoriasis?
Patches of skin that are dry, red (plaques) and covered in silver scales
Itchiness and soreness
Plaques may be cracked or bleeding
What is the macroscopic appearance of psoriasis?
Patches of red skin with plaques and covered in silver scales
What is the microscopic appearance of psoriasis?
Inflammatory cells: dendritic cells, macrophages, T cells
Over abundance of skin cells (keratinocytes)
Clubbed epidermal projections that interdigitate with dermis
Epidermal thickening
Granula layer can sometimes be missing
Most superficial cells aren’t fully matured (still have nucleus)
What is the pathophysiology of psoriasis?
Hyperproliferation of keratinocytes in the epidermis with an increase in the epidermal turnover rate
(Turnover very 3-5 days as opposed to 28-40)
What is colorectal carcinoma?
A malignant epithelial neoplasm of the colon/rectum
What are the predisposing factors for colorectal carcinoma?
- Old age
- Family history
- Diet high in red and processed meat
- Smoking and heavy drinking
- Obesity and inactivity
- Crohn’s disease and ulcerative colitis
What is the presentation of colorectal carcinoma?
- Persistent change in bowel habit- more often with looser stall and abdominal pain
- Blood in the stool
- Abdominal pain,bloating and discomfort always due to eating
What is the macroscopic appearance of colorectal carcinoma?
Ulcerated
Flat (sessile polyp)
Irregular margin
What is the microscopic appearance of colorectal carcinoma?
Large pleomorphic cells, with dark nuclei
Poor differentiation
Mitotic figures
What are the principals of staging a colorectal cancer?
Dukes staging A. Into but not through wall B. Through wall C. Lymph nodes D. Metastases (distant)
What is the screening programme for colorectal carcinoma?
M/F 60-74 screened every 2 years
74+ screened at request
Screen includes: bowel scope, testing for blood in stools
What is the presentation of uterine leiomyoma?
Heavy or painful periods
Abdominal and lower back pain
A frequent need to urinate and constipation
Pain and discomfort during sex
What is the macroscopic appearance of uterine leiomyoma?
Multiple tumours
Polyps (pedunculated)
Pushing the boundaries
What are the microscopic features of uterine leiomyoma ?
Elongates cigar shaped Nuclei
Well differentiated
Pushing boundaries
Storiform structure (elongated cells radiating from centre)
What is osteosarcoma?
Malignant neoplasm of the bone
What is the presentation of osteosarcoma?
- Persistent bone pain that gets worse over times and continues into the night
- Inflammation over a bone which can make movement difficult, if affected bone is near a joint
- Noticeable lump on bone
- Weak bone that fractures easily
What is the macroscopic effect of osteosarcoma?
Growth on bone, abnormal outlines
What are the microscopic features of osteosarcoma?
Pleomorphic malignant cells (all look different)
Less osteoid
Poorly differentiated cells
What is an ovarian teratoma?
Also called a dermoid cyst of the ovary, this is a bizarre tumor, usually benign, in the ovary that typically contains a diversity of tissues including hair, teeth, bone, thyroid, etc
What is the presentation of ovarian teratoma?
Pelvic pain and pain during sex
Difficulty emptying bowels and a frequent need to urinate
Irregular/abnormal periods
Bloating, a swollen abdomen and feeling full after eating only a little
What is the macroscopic appearance of an ovarian teratoma?
Cyst containing hair, sebum, teeth etc
What is the microscopic appearance of a ovarian teratoma?
Serbacous glands
Epidermis
Etc
What is the cell of origin for a dermoid cyst?
Germ cell
Growth of ectoderm, mesoderm and endoderm tissues (ie bone, hair, nerves)
What is a strums ovarii?
A rare form of monodermal teratoma that contains mostly thyroid tissue which may cause hyperthyroidism
What is chronic lymphocytic leukaemia?
A monoclonal disorder characterised by a progressive accumulation of functionally incompetent lymphocytes (B lymphocytes)
Common in adults over 50
What is the presentation of a chronic lymphocytic leukaemia?
- getting infections often
- anaemia and bleeding and bruising
- fever and night sweats
- swollen glands in neck, armpits and groin
- swelling and discomfort in the abdomen
- unintentional weight gain
What is chronic lymphocytic leukaemia a stage of?
Small lymphocytic lymphoma: the of B cell lymphoma which present primarily in the lymph nodes
What is melanoma?
Cancer of the melanocytes (skin cancer)
What are the predisposing factors for malignant melanoma?
- Repeated sunburn
- Radiotherapy treatment
- Lots of large moles/lots of freckles
- Family history
- Pale skin, fair hair, blue eyes
- HIV/immunosuppressants
- Previous diagnosis
What is the presentation of malignant melanoma?
A new mole or a change in a mole: getting bigger, changing in shape or colour, bleeding or becoming crusty, itchiness and soreness
What is the macroscopic appearance of malignant melanoma?
Mole on skin, large, variations in colour, asymmetrical shape, with irregular borders
What is the microscopic appearance of malignant melanoma?
Proliferation of melanocytes
Inflammatory cells
Squamous epithelium
Melanocytes in dermis and epidermis
What is pancreatic adenocarcinoma?
Malignant neoplasm of the pancreas (epithelium)
What is the macroscopic features of a pancreatic adenocarcinoma?
Large growth
What are the microscopic features of a pancreatic adenocarcinoma?
Rudimentary gland (the tumour is trying and failing to make glands)
What are the complications/symptoms of a pancreatic adenocarcinoma?
Weight loss Jaundice Pain Bowel obstruction Symptoms of diabetes
What is a carcinoid tumour?
Slow growing well differentiated neuroendocrine tumour originating in the cells of the neuroendocrine system
They can be found in the bowel, lung and stomach as well as other places
What is the presentation of a neuroendocrine tumour/carcinoid tumour that is found in the:
A) bowel
B) lung
C) stomach
A) bowel carcinoid tumour: abdominal pain, blocked bowel, rectal bleeding, diarrhoea and constipation
B) lung carcinoid tumour: cough which may include blood, wheezing, breathlessness, chest pain and tiredness
C) stomach carcinoid tumour: pain, weight loss, tiredness and weakness
What are the complications of carcinoid tumours?
Carcinoid syndrome: skin flushing in face and neck, chronic diarrhoea and dyspnea
Carcinoid heart disease: may secrete hormones that thicken the heart chambers, valves and blood vessels=leads to heart failure
Cushing’s syndrome: lung carcinoid tumour can cause this by releasing ACTH/CRH
What is Burkitt’s lymphoma?
Cancer of the lymphatic system, in particular the B cells found in the germinal centres.
Fasted growing human tumour
Associated with impaired immunity
Rapidly fatal if untreated
Name some predisposing factors for Burkitt’s lymphoma?
- Immunocompromised (HIV or in immunosuppressants)
- Autoimmune condition
- Previous exposure to EBV, HTLV, H.pylori infections
- Previous chemo/radiotherapy
- Coeliac disease
What is familial adenomatous polypsis?
Inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when they are left untreated
Multiple benign growths in the colon may develop as early as teenage years
What is an adenomatous polyp?
Polyps (abnormal growths) that grow on the lining of the colon and which carry a high risk of cancer, they are considered pre-malignant
What is the genetic change that gives rise to familial adenomatous polyposis?
Mutations in APC gene which affects the ability of cells to maintain normal growth and function
What is the macroscopic appearance of familial adenomatous polyposis?
Hundreds to thousands of colorectal polyps, small abnormalities in the intestinal tract
What are the complications of familial adenomatous polyposis?
Colorectal carcinoma
Duodenal or periampullary adenocarcinoma
Desmond formation
What is the treatment for familial adenomatous polyposis?
Surgery to prevent development of colon cancer
Sulindac and celecoxib can reduce the size and number of polyps in patients who have had surgery
What is hereditary non-polyposis colorectal cancer?
Most common form of colorectal carcinoma
What are the genetic changes that lead to the development of hereditary non-polyposis colorectal carcinoma?
Autosomal dominant syndrome due to defective mismatch repair protein (MMR)
What is retinoblastoma?
Cancer of immature cells of a retinue (light detecting tissue of eye)
What is the pathophysiology of a retinoblastoma?
Arises from a mulitpotential precursor cell that could develop into almost any type of inner or outer retinal cell
What is the presentation of retinoblastoma?
Normally occurs in those under 5 Unusually white reflection in the pupil Squinting or poor vision Colour change in iris Red or inflamed eye
What is xeroderma pigmentosum?
rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient
What are the genetic changes that occur to result in xeroderma pigmentosum?
Mutation in the genes that are involved in DNA repair:
XPC
ERCC2
POLH
What is the presentation of xeroderma pigmentosum?
Sever sunburn with only small amounts of exposure
Freckles at an early stage
Painfully sensitive eyes (to sun)
Rough surfaced growth/skin cancers
Blistering and freckles on minimum sun exposure
What is malignant mesothelioma?
Cancer of the pleura or the peritoneum
What is the predisposing factor for malignant mesothelioma?
Exposure to asbestos
What is the macroscopic appearance of a malignant mesothelioma
Thickening of the mesothelium
What are the predisposing factors for cervical cancer?
HPV (human papilloma virus) Smoking Weakened immuno system Taking the pill for more than 5 years Having children
What is the pathophysiology of HPV causing cervical cancer?
HPV expresses E6 and E7 proteins that inactive/inhibit tumour suppressor proteins: p53 and pRB (respectively)
Thus it:
Speeds cell through cell cycle
Inhibits apoptosis (because p53 is inhibited)
Combats cellular senescene
What are the screening and prevention methods put into place to reduce the cervical cancer?
HPV test and vaccinations
What are the predisposing factors for hepatocellular carcinoma?
Hep B/C
Alcoholism/liver cirrhosis
Aflatoxin
Haemochromatosis
What is the tumour marker used for hepatocellular carcinoma?
Serum alpha fetoprotein which will increase
What are the genetic changes seen in familial cases of breast cancer?
BRCA1 and BRCA2 abnormalities and mutations stop these genes from repairing cell damage
What are the predisposing factors for breast cancer?
Increased age Genetic mutations (BRCA1/2 genes) Early menstrual period (before age 12) Late or no pregnancy Starting menopause after 55 Physical inactivity/being overweight after menopause Having dense breasts
What is the macroscopic appearance of breast cancer?
Dimpling or puckering Rash crusting Nipple discharge (clear/ bloody) Change in nipple appearance (being pulled in) Lump
What two type of receptors can be identified within breast cancer tissue to establish the potential cause of the proliferation?
Oestrogen receptors (cancer is called oestrogen-receptor-positive) Her2 receptors
*both these substances may have stimulate the cancer cells to divide and grow
What are the two types of treatment for breast cancer?
Hormone therapy (limited scope but non toxic) Herceptin therapy (can have autoimmune side effects)
Describe how hormone therapy is used to treat breast cancer?
Used to treat oestrogen receptor positive cancers.
They bind to the receptors and prevent oestrogen from binding
Eg tamoxifen
Describe how herceptin therapy can be used to treat breast cancer
Used for cancers with large HER2 receptors, herceptin can block these and causes the cell to stop growing and death
What are the predisposing factors for squamous cell carcinomas of the skin?
Fair skin
Xs sun exposure, use of tanning beds and history of sunburns
Personal history of precancerous skin lesions and of skin cancer
What is the microscopic appearance of squamous cell carcinoma?
Islands of cells that look like epidermis, it will form keratin- pink fibrinolytic structures: looks like cabbage
What is the macroscopic appearance of squamous cell carcinoma of the skin?
Ulcerated red patch
Hard raised edges
What are the predisposing factors for a basal cell carcinoma?
Chronic sun exposure Radiation therapy for psoriasis or acne Fair skin Male Over 50 Personal or family history of skin cancer
What is the macroscopic appearance of basal cell carcinoma?
Red/brown abnormal lump/growths on skin
Raised (central ulceration)
What is the microscopic appearance of a basal cell carcinoma?
Peripheral palisade
Islands of dark cells in epidermis and dermis of skin
What is the behaviour of a basal cell carcinoma?
Rarely metastasises
Prognosis is excellent but if allowed to progress it can cause significant morbidly
Name 5 types of lung cancer
- Adenocarcinoma (cells lining lungs, gland like properties)
- Squamous cell carcinoma (squamous cell lining of resp. tract)
- Large cell carcinoma (poorly differentiated)
- Large cell neuroendocrine tumour (fast growing type)
- Small cell lung cancer (type of neuroendocrine tumour, fast growing cancer that rapidly spreads/metastasises)
What is the relationship between smoking and lung cancer?
Cigarette smoking is linked to 80-90% of lung cancer
At least 70 of the chemical in tobacco are known to be carcinogenic
What are the predisposing factors for bladder cancer?
Smoking
Increasing age
Being white
Being male
Exposure to harmful chemicals (eg arsenic)
Previous cancer treatment aimed at the pelvis
What is kaposi’s sacroma?
A cancer that causes patches of abnormal tissue grow under the skin/lining of mouth, nose and throat/ in lymph nodes etc
The patches are usually red or purple and are made of cancer cells, blood cells and blood vessels
What are some causes of Kaposi’s sarcoma?
Human herpesvirus 8 (HHV-8)- spread during sex, by saliva or vertically
Particularly at risk if you have a weakened immune system or have a genetic vulnerability to the virus
What are the two types of testicular cancer?
Seminoma and non-seminoma (teratoma, embryonal carcinoma, choricarcinoma, yolk sac tumours)
What are the macroscopic appearances of testicular cancer?
Abnormal lumps
Changes in size, shape or weight (compared to other testicle)
What are the tumour markers used for testicular cancer?
Alpha fetoprotein (AFP) Beta human chorionic gonadotropin Lactate dehydrogenase (LDH)
What is the presentation of a Hodgkin’s lymphoma?
Lymph node swelling in neck, armpits or groin Night sweats and fever Unintentional weight loss Persistent cough or dyspnea Persistent itching all over body
What is the microscopic appearance of Hodgkin’s lymphoma?
Multi-nucleated Reed-Sternberg cells in lymph nodes
Eosinophils (secreting IL5)
What is the staging method used for lymphomas?
Ann Arbor:
Stage 1- 1 node region
Stage 2- 2 separate nodes on 1 side of diaphragm
Stage 3- 2 separate nodes on different sides of diaphragm
Stage 4- involvement of extra-lymph nodula structures involved ie bone marrow/lungs
What is the macroscopic appearance of prostate cancer?
Enlarged prostate
Compressed urethra
What are the microscopic features of prostate cancer?
No glands Irregular cells Large nuclei Pleomorphic Apoptotic debris Poorly differentiated
How is prostate cancer graded?
Gleason grading system:
Stage 1. Cancer is small and only in prostate
2. Cancer is larger and may be in both lobes of prostate
3. Cancer had spread beyond prostate to nearby lump nodes/seminal vesicles
4. Cancer has spread to other organs like bone-metastatic
What is the tumour marker used for Prostate cancer?
PSA - prostate specific antigen
