Which conditions can lead to hypercoagulability?
Antithrombin III deficiency
Protein C or S deficiency
Factor V Leiden
How can immunohistochemistry be used in cancer?
What colour will proteins show up if present?
- Antibodies for cytokeratins can be used (family of around 20 intracellular fibrous proteins present in almost all epithelia) - will give information about primary site of cancer e.g. CK7+/CK20- can be present on lung cancer cells
- Antibodies for Her2 receptors - growth factor which can be used to predict the response of breast cancer to drug Herceptin
Proteins will show up brown if present
What kind of hypoxia does cyanide poisoning lead to? Why?
HISTIOCYTIC HYPOXIA
Cyanide poisoning leads to disabled oxidative phosphorylation.
It blocks the flow of electrons along the electron transport chain which means that H+ can’t flow out of the matrix into the intermembrane space.
This means no proton motive force is established so H+ doesn’t flow through ATP synthase –> no ATP –> needed for respiration in cells
What is ischaemic reperfusion injury? Why is it dangerous?
When blood is returned to a damaged but not yet necrotic area of tissue.
- FREE RADICALS - Increased production of free radicals with reoxygenation
- NEUTROPHILS - Increased neutrophils delivered to reperfused area - inflammation and tissue injury
- COMPLEMENT - Delivery of complement proteins and activation of complement pathways
What is graft vs host disease?
Pathological apoptosis - following a graft of foreign tissue, the cytotoxic T cells (?) from the graft tissue attack host cells causing them to apoptose
What is a1-antitrypsin deficiency?
What main complication can arise?
- What it is: an autosomal recessive disorder with varying levels of severity
- Pathophysiology: low levels of alpha-1 antitrypsin, a protease inhibitor which deactivates enzymes released from neutrophils at the site of inflammation. The liver produces a version of the protein α1-antitrypsin that is incorrectly folded. This cannot be packaged by the endoplasmic reticulum and accumulates within this organelle and is not secreted by the liver.
- Presentation: Breathlessness, jaundice, upper-left quadrant pain
- Complications: The systemic deficiency of the enzyme means that proteases within the lung can act unchecked and patients with the condition develop emphysema as lung tissue is broken down. Liver disease also occurs as the accumulated abnormal version of the protein causes hepatocyte damage and eventually cirrhosis.
How could you tell whether pleural oedema was due to pneumonia or heart failure?
Transudate = same protein content as blood plasma Exudate = higher protein content than blood plasma - only occurs in inflammation when vascular permeability is increased
Can take fluid from pleural oedema - if high protein then probably pneumonia.
If normal protein probably heart failure.
Which cytokines are particularly important?
IL-1, IL-6, TNFa - stimulate acute phase response = stimulates liver to produce CRP, complement factors, clotting factors, increase erythropoiesis in bone marrow.
Which organisms cause meningitis in different age groups?
Neonates (Up to 6 weeks old): group B strep (acquired from mother if she has it present in vagina), E.coli, listeria
Children: Same as young adults, plus haemophilus influenza
Young adults: Neisseria meningitidis, streptococcus pneumoniae
Older adults: Listeria, neisseria, strep pneumoniae
(Say Neisseria meningitidis other than for neonates)
What grading system is used for breast cancer?
Bloom-Richardson system grades according to presence of
- Tubules
- Pleomorphism
- Mitoses
Invasion of carcinoma cells involves altered adhesion, stromal proteolysis and motility.
What does altered adhesion involve?
Which proteases are involved in stromal proteolysis?
- Altered adhesion between malignant cells involves a reduction in E-cadherin expression.
- Altered adhesion between malignant cells and stromal proteins involves changes in Integrin expression.
- The cells must degrade basement membrane and stroma to invade.
- This involves altered expression of proteases, notably matrix metalloproteinases (MMPs)
What are the histiological features of TB and sarcoidosis?
TB - granulomas present, including Langhan’s giant cells, lymphocytes, epithelioid histiocytes and CASEOUS NECROSIS at the centre
Sarcoidosis - A granulomatous disease affecting lungs and lymph nodes of young adult women. Granulomas and giant cells present but without caseous necrosis.
Compare Crohn’s and Ulcerative Colitis
Crohn’s…
- Lesions are transmural and have a cobblestone appearance
- Shows discontinuous distribution (skip lesions)
- Affects any part of the GI tract (anal lesions therefore often seen – Crohn’s is moth to anus)
- Granulomas and crypt abscesses often seen
- Lymphocytes predominate
- Bowel fistulae more likely than in UC
Ulcerative colitis
- Inflammation limited to mucosa and submucosa - superficial
- But inflammation is continuous - many neutrophils present
- Distorted crypt architecture very common
- Significantly increased risk of colon cancer
- Often most severe in distal colon
- Colectomy often indicated
What does Helicobacter pylori do?
What will gut infected with it look like?
What are some complications of it?
- Role of Helicobacter pylori: Gram negative. Causes chronic gastritis by stimulating production of pro-inflammatory cytokines and by directly injuring epithelial cells and increasing acid secretion.
- Microscopic appearance
- Helicobacter pylori organisms present
- Chronic inflammation (and some acute inflammation) in the lamina propria and superficial epithelium
- Lamina propria fibrosis
- Mucosal atrophy
- Intestinal metaplasia
• Complications
o Gastric adenocarcinoma.
o MALT (mucosa associated lymphoid tissue) lymphoma.
What is scurvy? Why does it occur? What is its main complication?
Defect in collagen synthesis due to vitamin C deficiency - required for hydroxylation of procollagen.
Patients unable to heal wounds adequately –> tendency to bleed e.g. Gums
What is Ehlers-Danlos syndrome?
What does it lead to?
Type 3 collagen deficiency
- Skin is hyperextensible, fragile and susceptible to injury, hypermobile joints –> poor wound healing and joint dislocation
- Can lead to rupture of colon and large arteries, corneal rupture and retinal detachment
What is osteogenesis imperfecta?
What does it lead to?
Autosomal dominant condition
- Type 1 collagen deformity/deficiency - major component in ground substance of bone
- Too little bone tissue –> extreme fragility –> repetitive fractures and bowed limbs
- Blue sclerae due to too little collagen, making them translucent
- Can also have hearing impairment and dental abnormalities
What is Alport Syndrome?
What does it lead to?
Usually X-linked
Type VI collagen abnormal
- Disruption of glomerular basement membrane –> haematuria and chronic renal failure
- Dysfunction of cochlear or ear and lens of eye –> neural deafness and eye disorders
What is a transient ischaemic attack? What causes it?
Episodes of neurological dysfunction that appear suddenly and last minutes or hours and then disappear.
They are the result of microscopic emboli, usually atheroemboli, to the brain.
What does aspirin do and how?
Antithrombogenic.
Prevents platelets from producing thromboxane A2, a powerful platelet aggregator.
Prolongs bleeding time.
What does heparin do?
Forms irreversible complexes with antithrombin III resulting in its activation
What does warfarin do?
How are levels measured?
What is recommended dose and what classes as overdose?
Interferes with vitamin K metabolism - vitamin K is required to synthesis clotting factors, so inhibiting it means that clotting time will be prolonged.
INR is used as a measure of dose - ratio of patient’s PT to mean normal PT
Dose should be between 3-9mg/day
If INR >8 give vitamin K orally or IV
Why might someone have thrombocytopenia (low platelets?)
IMMUNE DESTRUCTION - Immune thrombocytopenic purpura - autoantibodies against glycoproteins on platelets –> petechia - treat with corticosteroids
DIC - Small clots in microcirculation - caused by malignancy, G- sepsis, massive tissue injury e.g. Burns, massive haemorrhage and transfusion. Raised PT/APTT, INR, fibrinogen and D-dimers.
Can lead to haemolytic anaemia as RBCs get damage by fibrin
DILUTION - due to blood transfusion
SEQUESTRATION in spleen
MARROW FAILURE e.g. Chemo, cancer/fibrosis, B12 or folate deficiency, HIV/hepatitis
What is haemophilia A? What are its symptoms? How would you test for it? And treat it?
How is haemophilia B different?
Haemophilia A is an X-linked condition
- Congenital lack of factor VIII
- Symptoms: bleeding into muscles, joints and post-operatively
- Test: ELISA test for factor VIII
- Treatment: Recombinant factor VIII or DDAVP to release factor VIII from stores
Haemophilia B
- Similar presentation to A, but due to reduction in factor IX
