Pathology Flashcards
(136 cards)
1
Q
Inflammatory Response - normal phases (6)
A
Vascular Exudative Resolution Supparation Organisation Chronic inflammation
2
Q
What is the vascular phase of inflammation and how long does it last
A
Lasts 15 mins to several hours. Up to 10 fold increase in blood flow increases the hydrostatic pressure and causes a transudate (low protein). Plasma protein leaks into the tissues due to the decreased intravascular oncotic pressure.
3
Q
What causes the increased vascular permeability of the vascular phase of inflammation?
A
Contraction of endothelial cells
4
Q
What are the three phases of the exudative phase?
A
Margination
Adhesion
Emigration
5
Q
Inflammation, exudative phase, what is margination
A
The loss of intravascular fluid due to a breach from injury causes increased plasma viscosity, so flow slows at the injury site allowing neutrophils to flow closer to the epithelium
6
Q
Inflammation, exudative phase, what is adhesion and what impairs it
A
Neutrophils adhere to the endothelial surface by increased expression of leukocyte adhesion molecule and increased expression of epithelial surface adhesion molecule
Impaired by diabetes, corticosteriod use, acute alcohol intoxication, inherited adhesion deficiencies
7
Q
Inflammation, exudative phase, what is emigration
A
Migration of neutrophils through the basement membrane by active amoeboid movement
8
Q
Inflammation, what is resolution
A
Back to normal state with regeneration of damaged tissue
9
Q
Inflammation, what is supparation
A
A persistent causative agent that leads to pus formation and becomes walled off by a pyogenic membrane that is inaccessible to the body’s defences.
10
Q
Inflammation, what is fibrosis
A
Where a large area of tissue is destroyed or unable to regenerate. The scar tissue is mainly collagen, inflexible and may impair function
11
Q
Inflammation, what is chronic inflammation
A
A persistent causative agent that lasts months to years. There is tissue destruction and cellular exudate changes. It is mainly dominated by macrophage, lymphocyte and plasma cells, and their toxins damage host tissue
12
Q
In the later stage of inflammation, what is chemotaxis
A
Neutrophils are attracted towards complement, IL8, leukotriene B4 and bacterial products
13
Q
What is opsonisation
A
This prepares a particle for phagocytosis by coating it in Ig or complement, thus marking it for destruction
14
Q
How do bacteria activate the complement pathway?
A
Bacterial polysaccharides activate the alternative complement pathway and generate C3b.
Antibodies bind bacterial antigens and activate the classical complement pathway and generate C3b
15
Q
What happens at the phagocytosis phase
A
Neutrophils send out pseudopodia around the opsonised particles which fuse, containing the particle in a phagosome bound by a cell membrane. Lysosomes bind with the phagosome forming a phagolysosome to begin intracellular killing
16
Q
Explain oxygen dependent intracellular killing
A
Neutrophils produce hydrogen peroxidase which reacts with myeloperoxidase to produce microbicidal agents. Oxygen is reduced by NADPH oxidase to produce free radicals.
17
Q
What does oxygen independent intracellular killing use?
A
Lysozymes, lactoferrin, acid hydrolase and defensins
18
Q
What happens in chronic granulomatous disease?
A
NADPH is deficient causing recurrent bacterial infections
19
Q
What happens in myeloperoxidase deficiency
A
Frequent candidal infections
20
Q
Chemical mediators - histamine
A
From mast cells, basophils and platelets. Stimulated by C3a, C5a, IgE, lysosomal proteins and physical injury
21
Q
Chemical mediators - serotonin
A
from platelets - causes vasodilation, increases vascular permeability and promotes chemotaxis
22
Q
Chemical mediators - lysosomal compounds
A
from neutrophils - causes vasodilation, increases vascular permeability and promotes chemotaxis
23
Q
Chemical mediators - Prostaglandins
A
From arachadonic acid
Thromboxane A2 - from platelets, causes vasoconstriction and platelet aggregation
Prostacyclin - from endothelium, inhibits platelet aggregation
Prostaglandin - causes pain
24
Q
Chemical mediators - Cytokines
A
From arachadonic acid
IL1 +TNF - causes fever, increases adhesion molecules and activates neutrophils
IL8 - chemotactic
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Complement C5a
Chemotactic
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Complement C3b, C4b, C2a
Oponin
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Complement C3a, C5a
Stimulates histamine release
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Complement C5b-C9
Membrane attack complex
29
The Kinin cascade
Activated by factor XII and leads to formation of bradykinin which causes vasodilation, increased vascular permeability, bronchoconstriction and pain
30
Beneficial local effects of inflammation (6)
Permits entry of antibodies leading to the breakdown of microorganisms, increased delivery of nutrients and oxygen, dilution of toxins and stimulation of the immune system
31
Harmful local effects of inflammation (2)
Damage to normal tissue
| Swelling (epiglottitis, compartment syndrome)
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Systemic effects of inflammation (5)
Malaise, anorexia, nausea, pyrexia, raised ESR
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Causes of leukocytosis - neutrophilia
Pyogenic infection
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Causes of leukocytosis - eosinophilia
Allergy and parasites
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Causes of leukocytosis - lymphocytosis
Chronic infection and viral
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Causes of leukocytosis - monocytosis
mononucleosis, some bacterial (TB, Typhoid)
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Causes of abnormal inflammation (9)
Genetic malformation, cancer, atherosclerosis, allergy, asthma, autoimmune, chronic inflammation, vasculitis, transplant rejection
38
What is CRP
An acute phase reactant hat rises dramatically with inflammation in response to increased Il6 released by macrophages. Rises more in bacterial infections than viral. It is synthesised and secreted by the liver. It binds phosphocholine opsonizing damaged or foreign cells for phagocytosis
39
What is Rheumatoid Factor
An autoantibody against the Fc portion of IgG. High levels indicate rheumatoid arthritis and Sjogren's syndrome. The sigher the level the higher the risk of a more destructive arthropathy.
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What is ANF
Antinuclear factor or antinuclear antibodies are autoantibodies against the cell nucleus, present in various disorders
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Specific subtype of ANF found in SLE
All ANF
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Specific subtype of ANF found in systemic sclerosis
All ANF, Scl-70
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Specific subtype of ANF Limited scleroderma
All ANF, anti-centromere
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Specific subtype of ANF Sjogren's syndrome
All ANF, anti-RO, Anti-La
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3 layers of the normal immune response
Physical, innate, adaptive
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Physical immune barriers (5)
```
Coughing and sneezing
Tears and urine to flush away
Skin and mucus
Commensal flora outcompete
Gastric acid neutralises most bacteria
```
47
What is the innate immune response
Non-specific. Initiated when microbes are identified from components common to large groups of microbes and when injured cells signal
48
What are the four main functions of the immune system?
Recruit immune cells to the site
Activate the complement cascade
Identify and remove foreign substances
Activate the adaptive response by antigen presentation
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First innate immune response is
Inflammation
50
Second innate immune response is
Cellular response - white cells (neutrophils, eosinophils, basophils and natural killer cells) identify and eliminate pathogens
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Third innate immune response
Complement cascade
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When is the adaptive immune response initiated?
When the innate response presents enough antigen
53
What is the function of the adaptive immune response
Recognises non-self
Generate specifically tailored immune responses to the particular pathogen
Develop a memory to remember the pathogen and allow easier elimination of subsequent infections
54
What are the main cellular components of the adaptive immune response
T and B lymphocytes
55
Explain the adaptive immune response: Antigens are presented to...
Naïve T lymphocytes which activate to become either cytotoxic CD4 cells or helper CD4 cells.
Cytotoxic T lymphocytes undergo rapid clonal expansion and travel in search of the antigen. Cells with the antigen are punctured and lysed by cytotoxins.
56
Activation of the T lymphocyte requires either
a strong signal or a prompt from a CD4 helper cell
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What happens after the infection resolves
Some T cells remain to form immune memory, ready to be quickly activated if the same pathogen returns.
58
What do CD4 helper cells do?
Manage the immune response and activation leads to the release of assorted cytokines
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What do B cells do?
Create antibodies - Y shaped proteins that identify and neutralise foreign material
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What are the 5 types of antibodies
IgA, IgD, IgE, IgG, IgM
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How are B cells activated
Antigen and signals from CD4 cells
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What do activated B cells do next?
Multiply and mature into plasma cells, which last 2-3 days and produce antibodies which bind antigens, opsonise and activate the complement cascade. 10% of plasma cells survive to form antigen specific immune memory cells to fight off repeated further infection.
63
What is a type 1 hypersensitivity reaction
Allergic - includes atopy, anaphylaxis and asthma. Provoked by re-exposure to a specific antigen. IgE mediated - released from mast cells and basophils
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What is type 2 hypersensitivity reaction
Cytotoxic, antibody dependent reaction where antibodies bind antigens on 'self' and mark for destruction.
IgG and IgM mediated of autoimmune thrombocytopenic purpura and haemolytic disease of the newborn
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What is type 3 hypersensitivity reaction
Immune complex disease - small antibody-antigen immune complexes are not cleared by macrophages and are deposited in tissues causing disease. IgG or IgM mediated eg SLE, polyarteritis nodosum
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What is type 4 hypersentivity reaction
Delayed hypersensitivity - eg Type 1 DM, MS.
| T cells mediated. T cells targeting specific 'self' cells proliferate and destroy on contact.
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What is Autoimmunity
Overactive immune response with a failure to distinguish self and non-self leading to immune attack of body tissues eg Autoimmune hepatitis, Goodpastures, MS, RA
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What is immunodeficiency
One or more components of the immune system are deficient or malfunctioning. It may be inherited or acquired.
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5 stages of wound healing
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Haemostasis
Inflammation
Reconstruction
Epithelialisation
Maturation
```
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Haemostasis stage of wound healing
Local vascular contraction, platelet plug formation and activation of the clotting cascade
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Inflammation stage of wound healing
Removes bacteria, foreign material and devitalised tissue to prepare the wound for healing. Prolongation of this stage causes increased macrophage activity and poor wound healing.
72
Reconstruction stage of wound healing
Fibroblasts synthesise collagen and elastin and contract to bring the wound edges together. Macrophages release growth factor to stimulate new blood vessel formation
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Epithelialisation stage of wound healing
In wounds that are closed epithelial coverage develops in 24-48 hours, impaired by surface debris, eschar or devitalised tissue
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Maturation stage of wound healing
The amount of scar tissue formed depends upon the forces that act across a wound. Strength is gained as collagen matures and further modelling and maturation occurs over 2years.
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Wound healing specific tissues - skin
may need delayed closure.
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Wound healing specific tissues - tendon
Reconstruction lasts 6 weeks and full strength is never regained, It heals with fibrous scar tissue, Controlled movement while undergoing reconstruction aids healing
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Wound healing specific tissues - Peripheral nerves - levels of injury (3)
Neuropraxia
Axonotmesis
Neurotmesis
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What is neuropraxia
Mildest form of injury - block or reduction of conduction across a segment with conduction preserved above and below
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What is Axonotmesis
Middle severity - neural tube intact but axons disrupted - likely to recover
80
What is Neurotmesis
Most severe - neural tube severed. Likely permanent without repair.
81
3 phases of bone repair
Reactive
Reparative
Remodelling
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Reactive stage of bone repair
Incorporates haemostatic and inflammatory stages of normal wound healing
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Reparative stage of bone repair
Incorporates reconstruction and epithelialisation. There is callous formation and lamellar bone deposition. Periosteal cells proximal to the fracture and fibroblasts in the granulation tissue develop into chondroblasts and form hyaline cartilage. Periosteal cells distal to the fracture develop into osteoblasts and form woven bone. These tissues grow and unite to forma fracture callus. Osteoblasts then replace the fracture callus with lamellar bone
84
Remodelling phase of bone healing
Lamellar bone is replaced with compact bone and is at 80% strength by 3 months. Full healing can take 18 months.
85
Wound healing specific tissues - Myocardial plus complications
Injury usually comes from infarction where coronary arteries are blocked causing cell death which is irreparable. Collagen scar formation can lead to arrhythmias or rupture
86
Wound healing specific tissues - brain
No reparative or regenerative function but sometimes other areas of the brain can take over function to compensate.
87
How is anaemia classified and what are the three types
By red blood cells size
Macrocytic - larger
Normocytic - normal
Microcytic - smaller
88
Causes of macrocytic anaemia (5)
Meagaloblastic anaemia - low B12 with or without concurrent low folate (either from poor intake or poor absorption)
Pernicious anaemia - poor absorption of B12 due to autoantibodies against intrinsic factor or the parietal cells that produce it
Gastric bypass surgery
Hypothyroidism
Methotrexate
89
Causes of microcytic anaemia
Issues with haem synthesis - iron deficiency
Issues with globin synthesis - thalassaemia
Lead poisoning
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Causes of normocytic anaemia
Acute blood loss
Anaemia of chronic disease - cytokine action or iron metabolism
Aplastic anaemia
Haemolytic anaemia
91
Investigations for anaemia
FBC, ESR, Ferritin, Serum iron, Transferrin, Serum B12 and folate. Occasionally a bone marrow biopsy is needed.
92
What is leukaemia
Malignant disease or blood or bone marrow causing an increase in WBC. It presents as bruising, bleeding, petechial haemorrhage, frequent infections, anaemia, fever, chills, night sweats, splenomegaly, weight loss.
93
Classification of leukaemia
Acute or chronic and then by cell line affected - lymphoblastic (lymphocytes - usually B cells) or myeloid (marrow cells that form RBC, eosinophils, basophils, neutrophils and platelets)
94
What are acute leukaemias
Feature a rapid rise in immature cells. Crowding makes the bone marrow unable to produce healthy cells. Requires quick treatment to prevent malignant cells spilling into the blood stream. Most common form of childhood leukaemia
95
What are chronic leukaemias
Feature an excessive build up of mature abnormal WBC that takes years or months to progress. More common in the elderly, but can be affect any age.
96
Acute lymphoblastic leukaemia
Most common in young children but can affect adults over 65. Survival 85% in children, 50% in adults
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Chronic lymphoblastic leukaemia
Most common in adults over 55, almost never occurs in children. Incurable but chemo can control symptoms
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Acute myeloid leukaemia
More common in adults than children and men more than women. Survival 40% at 5 years
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Chronic myeloid leukaemia
Mainly adults but some children. 90% survival at 5 years.
100
What is lymphoma
Lymphocyte cancers that present as a solid mass of lymphoid cells and are classified by cell type
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Types of lymphoma
Mature B cells - Burkitt's lymphoma, follicular, Hodgkin's
| Mature T cells and NK cells - Aggressive NK cell lymphoma, anaplastic large cell lymphoma
102
Signs and symptoms of lymphoma
Presents with night sweats, weight loss, lymph node enlargement and hepatosplenomegaly
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Investigations for lymphoma
Investigate with FBC, U&E, LFT, LDH, CXR, Staging CT and biopsy
104
What is myeloma
An incurable cancer of plasma cells - the B cells which make antibodies. Signs and symptoms vary, depending on the proteins released by the malignant plasma cells
105
Signs and symptoms of myeloma (5)
```
Bone pain /fractures
Infections
Anaemia
Renal failure
Neurological symptoms
```
106
Explain bone pain in myeloma
Plasma cells produce RANKL which binds osteoclasts and induces bone resorption. Bone lesions are lytic and cause hypercalcaemic
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Explain increased infection rate in myeloma
Decreased production and increased destruction of normal antibodies
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Explain renal failure in myeloma
Damage caused by hypercalcaemia and the deposition of light chains produced by the malignant plasma cell
109
Explain neurological symptoms in myeloma
Weakness, confusion and fatigue due to hypercalcaemia. Spinal cord syndromes from pathological fractures
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Investigations for myeloma
FBC, U&E, Ca, Seruma nd Urine electrophoresis for paraproteins like Bence-Jones. Skeletal survey, bone marrow biopsy, Ig levels and B2 - microglobulin
111
Treatment for myeloma
High dose chemo to induce remission. Younger patients may get a bone marrow transplant
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Low platelet count disorder - What is throbocytopenia
Causes low platelet count, eg ITP - autoantibodies against platelets
113
Low platelet count disorder - What is Aplastic anaemia
Bon marrow failure secondary to autoimmune, toxins or infection. Causes pancytopenia as the bone marrow fails to make new cells
114
Low platelet count disorder - What is Gaucher's disease
A lysosomal storage disease where lipids accumulate in cells and tissues including the bone marrow, resulting in pancytopenia.
115
High platelet count disorder - What is thrombocytosis (primary and reactive)
Primary thrombocytosis isa myeloproliferative disorder causing increased risk of thrombosis and may progress to AML or myelofibrosis.
Reactive thrombocytosis can be due to inflammation, hyposplenia or asplenia
116
Platelet dysfunction disorder - HELLP syndrome
A variant of pre-eclampsia
| Haemolytic anaemia, Elevated Liver enzymes, Low Platelets.
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Platelet dysfunction disorder - Haemolytic Uraemic Syndrome
Toxins from enterohaemorrhagic E Coli cause haemolytic anaemia, acute renal failure and thrombocytopenia, mostly in children
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Platelet dysfunction disorder - Dengue
Viral haemorrhagic fever caused by flavivirus
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Platelet adhesion disorder - Von Willebrand disease (4 types)
Type 1 - heterozygous - decreased levels of vwf
Type 2 - qualitative defect
Type 3 - homozygous, most severe
Type 4 - platelet type - defect in the VWF receptor on the platelet
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Inherited coagulation disorders (2)
Von Willebrand Disease
| Haemophilia - recessive X linked disorder affecting clotting factors
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Haemophilia A
Factor VIII deficiency, most common
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Haemophilia B
Factor IX Christmas disease
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Treatment of haemophilia
Infusions of the missing factor, but some people develop antibodies tot he replacement an therefore need larger amounts or nonhuman factor
124
Causes of acquired coagulation disorders (4)
Toxins
Infections
Liver failure
DIC
125
Toxins or drugs that cause acquired coagulation disorder
Rattlesnake and viper venom
| Warfarin
126
Actions of warfarin
Inhibits vitamin K dependent synthesis of clotting factors II, VII, IX, X, protein C, protein S and protein Z which regulate the clotting process
127
Infections that cause acquired clotting disorder
Viral haemorrhagic fever - multifactorial aetiology - hepatic damage, consumptive coagulopathy, primary marrow dysfunction
128
How does liver failure cause an acquired clotting disorder
decreased protein syntesis
129
Acquired clotting disorders - DIC
A consumptive coagulopathy leading to depletion of platelets and clotting factors. Micro-emboli form in the vascular system, threatening end organ function.
130
Causes of DIC
```
Cancer (lung, pancreas, stomach)
Eclampsia
Amniotic fluid embolus
Massive trauma
Burns
Infection (Gram negative sepsis, strep pneumonia, malaria)
Snake/scorpion venom
```
131
What is thrombophilia
An abnormality causing hypercoagulability - can be congenital or acquired
132
Congenital causes of thrombophilia - Factor V Leiden
Factor V is a cofactor of Factor X that leads to activation of thrombin and is broken down by Protein C to limit clotting. Factor V Leiden is a form of factor V that cannot be broken down by Protein C.
133
Congenital causes of thrombophilia - Protein C deficiency
Protein C is an anticoagulant that inhibits Factor V and Factor VIII
134
Congenital causes of thrombophilia - Protein S deficiency
Protein S is a vitamin K dependent anticoagulant that acts as a cofactor to protein C
135
Acquired causes of thrombophilia - antiphospholipid antibodies
Autoimmune issue. Has various forms that cause either up regulation of prothrombotic factors or inhibition of antithrombotic factors or a combination of the two.
136
Signs and symptoms of thrombophilia
DVT, PE, clots in unusual places - venous sinus thrombosis, portal vein thrombosis, hepatic vein thrombosis, mesenteric vein thrombosis, renal vein thrombosis, recurrent miscarriage
