Pathology Flashcards
1
Q
What are the signs of a shocked patient
A
Pale, cold, clammy skin (peripheral vasoconstriction) Sweating rapid, shallow breathing (tachypnoea) Weakness and dizziness Hypotension (can be postural) tachycardia feeling sick and possibly vomiting Thirst Pyrexia in sepsis Oliguria (indicator of kidney function)
2
Q
What is the treatment of choice for acute shock
A
Treatment with synthetic colloids as immediate fluid of choice and also need to treat the underlying cause
3
Q
How can the red cell membrane get damaged
A
Mechanical damage (e.g. passing through a damaged valve)
Deposition of fibrin in small blood vessels causes mechanical damage (seen in E. coli 0157)
Inherited membrane defects (hereditary spherocytosis etc)
Autoimmune or alloimmune reactions
Inflammation
Oxidative stress
4
Q
What is a spherocyte
A
Abnormal RBC
Its membrane is tight, and the biconcave shape has been lost (circular)
Still contains the same amount of Hb
5
Q
Why are red blood cells more vulnerable to oxidative damage
A
Due to their close relationship with oxygen binding, as well as the dangers of oxidised iron
Also linked to water so can easily form H2O2
6
Q
What happens to the red cells in spherocytosis
A
The RBCs are spherical rather than biconcave
Genetic defect leading to structural problems with the red cell membrane
The membrane can get stripped off as it struggles to squeeze through the vessels
The blood cell becomes smaller and spherical to try and protect itself
Spleen will become enlarged as it tries to cope with getting rid of the damaged cells
7
Q
How do you treat hereditary spherocytosis
A
Long term treatment involves splenectomy
Can give folic acid
Treat the underlying trigger – infection
8
Q
What are the signs and symptoms of spherocytosis
A
Intermittent jaundice and fatigue
Can be triggered by infections
Folate deficiency
9
Q
What are the main form sof haemoglobin
A
HbA - 2A and 2B chains
Most common form in adults
HbA2 - 2A and 2delta chains
Seen in B-thalassaemia
HbF - 2A and 2gamma chains
Foetal Hb
10
Q
On which chromosome are the alpha globin genes found
A
Chromosome 16
There are 2 alpha genes per chromosome
Therefore 4 per cell
11
Q
On which chromosome are the beta globin genes found
A
Chromosome 11
There is 1 beta gene per chromosome
Therefore 2 per cell
12
Q
At what age are the adult level of Hb reached
A
6-12 months
Therefore beta chain issues don’t present until then (still have function HbF until then)
13
Q
What are haemoglobinopathies
A
Hereditary conditions affecting globin chain synthesis
Includes thalassemia’s (make less globin) and structural Hb variants
14
Q
What type of inheritance do haemoglobinopathies follow
A
Autosomal recessive
To have a condition you generally have to have inherited two copies
If you only get one copy, you have the trait or carry it
15
Q
What is affected in alpha thalassaemia
A
The alpha globin chains
16
Q
What is affected in beta thalassaemia
A
The beta globin chains
17
Q
What is thalassaemia
A
Reduced globin chain synthesis resulting in impaired haemoglobin production
Leads to a microcytic hypochromic anaemia
Can have toxic accumulation of globin chains and haemolysis
18
Q
What causes alpha thalassaemia
A
Results from deletion of one or both alpha genes from chromosome 16
If one its called A+
If both its called A0
19
Q
Which types of Hb are affected by alpha thalassaemia
A
All types - HbA, HbA2 and HbF
Alpha chains are present in all of them
20
Q
What are the different classifications of alpha thalassaemia
A
α thalassaemia trait; one or two alpha genes missing
HbH disease; only one alpha gene left
Hb Barts hydrops fetalis; no functional α genes
21
Q
Describe alpha thalassaemia trait
A
Asymptomatic carrier state
May have microcytic, hypochromic red cells with mild anaemia
Don’t really need treatment
22
Q
Describe HbH disease
A
Type of alpha thalassaemia with only one working gene Common in SE Asia
Will present with anaemia with very low MCV and MCH
Jaundice, splenomegaly, may need transfusion
23
Q
What happens to B globin chains in HbH
A
Excess β chains form tetramers (β4) called HbH
B chains want to bind to something – if you don’t have A chains due to thalassemia then they bind to each other
This is non-functional
24
Q
Which ethnicity has a high incidence of a-thalassaemia
A
SE Asian
Higher risk of more severe forms if both parents from Se Asia
25
What are the clinical features of Hb hydrops foetalis syndrome
Profound anaemia
Cardiac failure
Growth retardation
Severe hepatosplenomegaly
Skeletal and cardiovascular abnormalities
Almost all die in utero - incompatible with life
26
What type of Hb is affected by B-thalassaemia
Only HbA
This is the only type that contains B chains
Therefore can make foetal Hb but not adult
27
What type of mutation usually causes B thalassaemia
Point mutations
28
What can cause iron overload
Hereditary haemochromatosis - primary
| Secondary - transfusional and iron loading anaemias
29
What causes hereditary haemochromatosis
Mutations in the HFE gene
Decreases synthesis of hepcidin
Increased iron absorption and gradual accumulation
30
What are the clinical features of hereditary haemochromatosis
```
Weakness/fatigue
Joint pains
Impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy
May be asymptomatic until end organ damage has occurred
```
31
When does hereditary haemochromatosis usually present
In middle age or later
| Very gradual process
32
How do you diagnose hereditary haemochromatosis
Genetic test - look for mutations
Transferrin saturation - increased
Serum ferritin - increased
Liver biopsy
33
How do you treat hereditary haemochromotosis
Weekly venesection
Keep doing it until you get their iron stores low enough
Then repeat a few times a year to prevent it rising again
Family screening
34
What can cause an iron loading anaemias
Repeated red cell transfusions
Excessive iron absorption related to over-active erythropoiesis - thalassaemia, sideroblastic anaemia
Red cell aplasia
35
How can you treat secondary iron overload
Iron chelating agents
Desferrioxamine (subcut or IV infusion)
They bind to iron and form a complex that is then excreted to reduce iron load
36
Why can you not treat secondary iron overload with venesection
The patients are usually already anaemic
37
What are the classifications of B thalassaemia
β thalassaemia trait - asymptomatic carrier trait
β thalassaemia intermedia - moderate severity
β thalassaemia major - unable to make adult Hb
38
What is the difference between β+ and β 0
β+ will have reduced β chain production
| β0 will have absent chain production
39
How does β thalassaemia present
```
Presents aged 6-24 months (as HbF falls)
Pallor, failure to thrive
Extramedullary haematopoiesis causing;
Hepatosplenomegaly
Skeletal changes - marrow expands
Organ damage
```
40
How do you manage β thalassaemia major
Regular transfusion programme to maintain Hb at 95-105g/l
This suppresses ineffective erythropoiesis and inhibits over-absorption of iron
Bone marrow transplant may be an option
41
What are the consequences of iron overload
Endocrine dysfunction - impaired growth and puberty, diabetes, osteoporosis
Cardiac disease - cardiomyopathy, arrhythmias
Liver disease - cirrhosis, hepatocellular cancer
42
What can cause sickle cell disorders
Point mutation in codon 6 of the β globin gene
| This alters the structure of the resulting Hb which distorts the red cell
43
Describe sickle cell trait
One normal, one abnormal β gene
Asymptomatic carrier state
May sickle in severe hypoxia eg high altitude, under anaesthesia
Blood film normal
44
What is the issue with sickle cells
HbS polymerises if exposed to low oxygen levels for a prolonged period
45
What causes sickle cell anaemia
Two abnormal β genes
| HbS will be over 80% with no HbA
46
What happens in sickle cell anaemia
Episodes of tissue infarction due to vascular occlusion – sickle crisis (very painful)
Chronic haemolysis – shortened RBC lifespan
Sequestration of sickled RBCs in liver and spleen
Hyposplenism due to repeated splenic infarcts
47
What can precipitate a sickle crisis
```
Hypoxia
Dehydration
Infection
Cold exposure
Stress/fatigue
```
48
What happens in a sickle crisis
Tissue ischaemia due to the sickle cells occluding vessels
| Leads to pain in that area
49
How do you treat sickle crisis
```
Opiate analgesia
Hydration
Rest
Oxygen
Antibiotics if evidence of infection
Red cell exchange transfusion in severe crisis eg (lung) chest crisis or (brain) stroke
```
50
What is the long term management of sickle cell anaemia
Prophylactic penicillin and vaccinations due to hyposplenism
Folic acid supplementation
Hydroxycarbamide - induces HbF production which can reduce severity
Regular transfusion to prevent stroke in some patients
51
How do you diagnose haemoglobinopathy
FBC; Hb, red cell indices
Blood film
Ethnic origin
High performance liquid chromatography (HPLC) or electrophoresis to quantify haemoglobins present
52
What is compensated haemolysis
Increased red cell destruction compensated by increased red cell production
Some patients' are able to compensate so aren’t anaemic
53
What happens when haemolysis cannot be compensated for
Haemolytic anaemia
The Hb falls
Bone marrow cant keep up
54
What are the sequelae of haemolysis
```
Erythroid hyperplasia (increased bone marrow red cell production)
Excess red cell breakdown products eg billirubin
```
55
How can you detect haemolysis
Increased red cell production
| Detection of breakdown products
56
What is the normal bone marrow response to haemolysis
Reticulocytosis
| Erythroid hyperplasia
57
What is extravascular haemolysis
The blood cells are taken up by the spleen and liver (reticuloendothelial system)
58
What is intravascular haemolysis
Red cells destroyed within the circulation
| They spill their contents into the bloodstream
59
Which type of haemolysis is more common
Extravascular
60
What are the signs of extravascular haemolysis
Hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)
Unconjugated bilrubinaemia which leads to jaundice and gall stones
Urobilinogenuria - bilirubin in the urine
61
What are the signs of intravascular haemolysis
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia - albumin
Haemoglobinuria: pink urine, turns black on standing
Haemosiderinuria - iron product in the urine
62
What can cause intravascular haemolysis
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria
63
Which type of haemolysis is more life threatening
Intravascular
64
How do you investigate haemolysis
```
Identify haemolysis:
FBC
Reticulocyte count
Serum unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen
```
Identify cause:
History
Blood film
Direct coombes test
65
Which test can exclude haemolysis
Haptoglobins
| If these are normal it pretty much excludes haemolysis
66
What can cause autoimmune haemolysis
```
Idiopathic
Autoimmune disorder - SLE
Lymphoproliferative disorders
Drugs - penicillin's
Infections
```
67
What can cause alloimmune haemolysis
Haemolytic transfusion reaction - antibody immune response
Can be immediate (IgM)- usually intravascular
Delayed (IgG) - extravascular
Haemolytic disease of the newborn - antibodies are transferred from mum
68
What causes of mechanical red cells destruction can lead to haemolysis
```
Disseminated intravascular coagulation
Haemolytic uraemic syndrome (eg E. coli O157)
TTP
Leaking heart valve
Infections e.g. Malaria
Burns
```
69
Which conditions can lead to RBC membrane defects that cause haemolysis
```
Liver Disease (Zieve’s Syndrome)
Vitamin E deficiency
Paroxysmal Nocturnal Haemoglobinuria
```
70
How does Zieve's syndrome present
Anaemia
Haemolysis
Polychromatic macrocytes
Irregularly contracted cells
71
Name a congenital cause of red cell membrane abnormalities
Hereditary Spherocytosis
| Leads to haemolysis
72
Which drugs are common causes of oxidative stress
Dapsone
| Salazopyrin
73
How does sickle cell disease lead to haemolysis
Affects physical properties of haemoglobin (abnormal polymerisation) resulting in shortened red cell survival
74
What is the definition of shock
A syndrome in which tissue perfusion is inadequate for the tissue’s metabolic requirement
Covers a wide range of causes
75
What does normal tissue perfusion rely on
Cardiac Function
Capacity of vascular bed
Circulating blood volume
76
How can you estimate perfusion
BP is most common surrogate
MAP
Can use different things for different organs – lactate, urine output, blood pressure
77
What can cause hypovolaemic shock
Acute haemorrhage
Dehydration, vomiting and burns all reduce plasma volume and can lead to shock – don’t have to lose whole blood
Don’t have sufficient volume for perfusion
78
What can cause cardiogenic shock
Primarily ischaemia induced myocardial dysfunction (MI)
| Also: cardiomyopathies, valvular problems, dysrhythmias
79
What can cause obstructive shock
Direct obstruction to cardiac output – PE, air-embolism
Restriction of cardiac filling – tamponade, tension pneumothorax
80
What can cause distributive shock
Septic, anaphylaxis, acute liver failure, spinal cord injuries
Due to disruption of normal vascular autoregulation, and profound vasodilatation
81
What are some endocrine causes of shock
Severe uncorrected hypothyroidism, Addisonian crisis – both reduced CO and vasodilation
82
What is the most common type of shock
Distributive (septic)
83
Describe the neuroendocrine response to shock
Release of pituitary hormones – Adrenocorticotrophic Hormone, Anti-diuretic hormone, endogenous opioids
Release of cortisol – fluid retention, antagonises insulin
Release of glucagon
84
How does the inflammatory response impact shock
Triggered by the cellular ischaemia
Cause a vicious cycle of vasoconstriction and oedema – worsening cellular ischaemia – as well as direct cytotoxic damage.
85
Describe the haemodynamic changes that can occur in shock
Vasodilatation, or constriction
Maldistribution of blood flow
Capillary abnormalities - AV shunting, “stop-flow” or “no-flow” capillary beds, failure of capillary recruitment, increased capillary permeability
Inappropriate activation of coagulation system.
DIC
Reperfusion injuries
86
Why is there a failure of vascular smooth muscle contraction in shock
Inflammation pathways activate a form of nitric oxide in vessel smooth walls
NO causes smooth muscle to relax
87
What are some of the causes of eosinophilia
```
Allergic reactions
Severe skin conditions - atopic dermatitis
Asthma
Parasitic infections
Hodgkin's and T cell lymphomas
Pulmonary syndromes
```
88
What are the roles of neutrophils
Phagocytosis
| Chemoattraction of other immune cells
89
What does the presence of immature neutrophils in the circulation suggest
Marrow stress or damage
| Shouldn't usually be able to get out
90
What can cause neutrophilia
```
Neoplasia
Inflammation
Tissue necrosis
Bacterial infection
Acute haemorrhage
```
91
What can cause basophilia
Polycythaemia rubra vera
| Chronic myeloid leukaemia
92
What are the functions of eosinophils
They release their granular contents which can damage parasites and surrounding tissues
This signals other cells in the inflammatory response to come to the area
Release T cell regulatory cytokines
93
What is released from mast cells when they degranulate
Mast cell tryptase - can be measured as a marker
Histamine
Heparin
94
Where do lymphocytes arise and develop
Arise in bone marrow
| Develop in primary lymphoid tissue - bone marrow and thymus
95
Describe class 1 hypovolaemia
<15% approx. blood loss
All other parameters normal
Requires monitoring
96
Describe class II (mild) hypovolaemia
```
15-30% approx. blood loss
HR normal or raised
Pulse pressure decreased
Base deficit = -2 to -6
May need transfusion
```
97
Describe class III (moderate) hypovolaemia
```
30-40% approx. blood loss
Increased HR and potentially RR
Decreased BP, pulse pressure, urine output and GCS
Base deficit = -6 to -10
Will require blood products
```
98
Describe class IV (severe) hypovolaemia
```
Over 40% approx. blood loss
HR and RR increased
Decreased BP, pulse pressure, urine output and GCS
Base deficit = -10 or less
Start massive transfusion protocol
```
99
What should you monitor in a patient with shock
Examination – Pale, cold skin, prolonged capillary refill.
BP
CO
Urine output – Sensitive indicator of renal perfusion
Neurological – Disturbed consciousness a good indicator of cerebral hypoperfusion
Biochemical – Acidosis, lactate levels
100
How can you monitor BP in a shocked patient
Cuff - uninvasive
| Arterial line
101
How do you monitor CO
Gold standard – Thermodilution with a PA catheter (rare)
Pulse contour analysis
Doppler ultrasonography
102
What is the immediate management of shock
ABC approach
Establishment of reliable, wide bore IV access and resuscitate while investigating
103
What is the purpose of giving fluids
Increase the preload and therefore increase CO
104
What is the risk of prescribing fluids in shock
Fluid overload
Shocked patients more susceptible to pulmonary oedema due to microvascular dysfunction
Can lead to PO/ARDS, bowel oedema etc
105
What is a fluid challenge
Rapid administration of a fluid, with an assessment of response
Typically – 300-500ml over 10-20 mins.
Can be repeated, but if “non-responsive” should be stopped
106
What are the pros and cons of prescribing crystalloids
Pro = convienient, cheap and safe
Con - rapidly lost from circulation to extravascular space (need large volume)
Includes saline
107
What are the pros and cons of prescribing colloids
Pros = Cheap(ish), reduce volumes required
Cons: Can cause anaphylaxis, no evidence of benefit
108
What are the pros and cons of prescribing blood products
Pros = has oxygen carrying capacity, will stay in circulation.
Cons = a scarce resource, and multiple risks
109
Which drugs can be used in the treatment of shock
Adrenaline (Epinephrine)
Noradrenaline (Norepinephrine) - usually first choice
Vasopressin (ADH)
Dopamine
110
Why are adrenaline and nor-adrenaline used in the treatment of shock
Alpha/beta agonists
| Affects HR, contractility and causes vasodilation
111
When are drugs used in the treatment of shock
When the fluids are no longer working on their own
| Used in addition
112
What happens if drugs and fluids don't work in the treatment of shock
Mechanical support options
In cardiogenic shock: balloon pumps, L-VADs, R-VADs
In severe cases – VA-ECMO (mechanical perfusion)
113
How do you manage hypovolaemia
Assessment of bleeding – estimation of volume loss, and speed of ongoing loss.
Establish source – may require imaging if stable
Temporisation – Direct pressure, tourniquet’s
Damage limitation resuscitation – until definitive control
Damage limitation surgery
114
Describe de-escalation in the shocked patient
Important to remove extra fluid from a patient once their shock has resolved
Various means: Spontaneous, Diuretic, Dialysis
115
Why do red cells clump together in infection
The positive charge of the acute phase proteins released during infection prevents the negative RBCs from repelling each other
This leads to an increased ESR
116
What is toxic granulation
When you see more granules in the WBC
| Seen in neutrophils during infection
117
How can coeliac disease present on a blood film
You get abnormal blood cells as the spleen isn't working well enough to filter them - hyposplenism
118
What can infected mononucleosis be a sign of
Most commonly glandular fever caused by EBV
| Can also be seen in HIV and CMV
119
What is pancytopenia
A deficiency of blood cells of all lineages
| Generally excludes lymphocytes
120
What can cause pancytopenia
Reduced cell production - bone marrow failure
| Increased destruction - hypersplenism
121
What characterises inherited marrow failure syndromes
Arise due to defects in DNA repair/ribsosomes
| Characterised by impaired haemopoesis, cancer pre-disposition and congenital anomalies
122
What are the features of Fanconi's anaemia
```
Short stature
Skin pigment abnormalities - café au lait
Radial ray abnormalities
Hypogenitilia
Endocrinopathies
GI defects
Cardiovascular
Renal
Haematological issues - pancytopenia
```
123
List examples of acquired primary bone marrow failure causes
Idiopathic aplastic anaemia
Myelodysplastic syndromes (MDS)
Acute leukaemia
All intrinsic problems with the marrow
124
What is aplastic anaemia
When there is an autoimmune attack against haemopoietic stem cell(s)
Therefore don't produce the differentiated cells
125
Describe myelodysplastic syndromes
There is dysplasia (disorder development) in the marrow
Hypercellular marrow
Increased apopotosis of progenitor and mature cells (inefffective haemopoiesis)
126
What can myelodysplastic syndromes develop into
Propensity for evolution into AML
127
Why can acute leukaemia cause pancytopenia
It causes proliferation of abnormal cells from the leukaemic stem cells
Fail to develop onto normal or mature cells
It hijacks the haemopoietic process which prevents normal HSC development - reduces other normal cells
128
List causes of secondary bone marrow failure
Drug induced aplasia - e.g. chemo
B12/folate deficiency - affects nuclear maturation in all lineages
Infiltration - non-haemopoietic malignant infiltration, lymphoma
HIV and other viral causes
Storage disease
129
List causes of hypersplenism
Splenic Congestion - portal hypertension, congestive cardiac failure
Systemic diseases - Rheumatoid Arthritis (Felty’s)
Haematological diseases- Splenic lymphoma
130
What are the clinical features of pancytopenia
Anaemia
Neutropenia - infections
Thrombocytopaenia - bleeds
Oher symptoms related to the exact cause
131
How would you investigate a pancytopaenia
```
History and clinical finding
FBC and Blood film
Further bloods guided by above - B12/folate, LFT etc
Bone marrow examination
Cytogenetics
```
132
In which condition is the marrow hypocellular
Aplastic anaemia
133
In which condition is the marrow hypercellular
Myelodysplastic syndromes
B12/folate deficiency
Hypersplenism
134
How do you treat idiopathic aplastic anaemia
Immunosuppression
135
What is the supportive treatment for pancytopenia
Red cell transfusions
Platelet transfusions
Antibiotics prophylaxis/treatment
136
What is the definitive treatment for pancytopenia
Treat the underlying cause
| e.g. cancer = chemo, treat viral cause etc
137
Describe the pathogenesis of AL amyloidosis
Problem with the plasma cells
Mutation in the light chain causes an altered structure
Precipitates in tissues as an insoluble beta pleated sheet
Accumulation in tissues causes organ damage
138
How do you treat AL amyloidosis
With chemo similar to myeloma to switch off light chain supply
139
How can AL amyloidosis present
```
Often presents late with organ damage
Nephrotic syndrome
Cardiomyopathy
Hepatomegaly and deranged LFTs
Neuropathies - autonomic and peripheral
Malabsorption
```
140
How do you diagnose amyloid
Organ biopsy confirming AL amyloid deposition - stained with congo red
SAP scan - shows up deposits in other organs
Can be used for monitoring
Echocardiogram/cardiac MRI
Nephrotic range proteinuria
Shows affects on these organs
141
What can lead to a polyclonal increase in immunoglobulins
Infection
Autoimmune
Malignancy- reaction of the host to the malignant clone
Liver disease
142
What can cause a monoclonal rise in immunoglobulins
Marker of underlying clonal B-cell disorder
| Means all Ig is derived from a single parent B cell
143
How do you detect immunoglobulins
Serum electrophoresis
The separated serum proteins appear as distinct bands
Abnormal bands will stand out
144
What are bence-jones proteins
Excess immunoglobulin free-light chains that are secreted into the urine
145
What can lead to an increase in the amount of free light chains
Polyclonal increase in plasma cells - seen in infection
| Monoclonal increase - multiple myeloma
146
List reactive causes of high granulocyte counts
Infection: eg pyogenic bacteria causing neutrophilia
| Physiological eg post-surgery, steroids
147
List reactive causes of high platelet counts
Infection
Iron deficiency
Malignancy
Blood loss
148
List reactive causes of high RBC counts
Dehydration
Diuretics
Secondary polycythaemia (eg hypoxia-induced)
149
List different types of bruising
Ecchymoses - typical bruise, caused by bleeding into the skin or sub-dermal tissues
Purpura - non-blanching, small, purple or brownish-red macular lesions due to
intradermal bleeding
Petechiae - non-blanching, pin-head, red, macular lesions due to intradermal capillary bleeding
150
What can cause easy bruising
It may be the only clinical indication of an underlying
haemorrhagic disorder
Characteristic of primary haemostatic failure like thrombocytopaenia but may also occur with secondary haemostatic failure like haemophilia
Also liver disease and malignancy
