Histopathology Flashcards
1
Q
What are the most commonly run chemical pathology tests?
A
- Electrolytes (esp. Na + K)
- Urea & Creatinine
- Calcium & Phosphate
- Liver Function (LFTs = liver enzyme measurements)
- Hormone Assays
- Glucose
2
Q
Anticoagulants are added to samples - what is the purpose of the following:
(a) EDTA
(b) Fluoride Oxalate
A
(a) EDTA = potassium = maintains cells
(b) Fluoride Oxalate = poison
3
Q
What 5 qualities should all diagnostic tests have?
A
- Specificity
- Sensitivity
- Rapid
- Non-invasive
- Cost effective
4
Q
What can virological tests detect?
A
- Inefctious virus
- Viral protein componenets (i.e. antigens)
- Viral genetic components
- Host response
5
Q
List some of the potential sample sites for virological sampling
A
- Throat swap, NPA, broncheolar lavage etc. = resp. viruses
- Stool = GI viruses
- Urine = UT viruses
- CSF = viruses capable of crossing BBB (eg: herpes)
- Blood = serology (i.e. antibody detection)
- Saliva = serology
6
Q
Briefly outline what the following techniques are used for (in reference to diagnostic virology)
- EM
- Immunofluorescence
- Serology
- Quantification Assays
A
- EM
- Visualisation of viral structures
- Immunofluorescence
- Detection of viral antigens
- Serology
- Detection of antibodies
- Quantification Assays
- Measuring viral load
7
Q
With regards to diagnostic microbiology, what is the optimal time for the collection of specimen?
A
In the acute phase of illness
Before antimicrobials have been started
8
Q
Give an example of a sterile and non-sterile culture site for diagnostic microbiology
A
Sterile = blood or CSF
Non-sterile = skin or throat swab
9
Q
Briefly outline what the following techniques are used for (in reference to diagnostic microbiology)
- Microscopy
- Serology
- PCR
A
- Microscopy
- Gram-staining, identification of bacteria
- Serology
- Monitor Ab response, identification of bacteria
- PCR
- Used to detect MRSA
10
Q
Define the role of a cytopathologist
A
Cytopathologists make diagnoses on cells
11
Q
Define the role of a histopathologist
A
Histopathologists make diagnoses based on tissue
12
Q
List some of the uses of clinical immunology
A
- Immunodeficiency
- Malignancy
- Auto-immunity
- Inflammation
- Tissue typing
- Histopathology
- Diagnostics
13
Q
Define inflammation
A
Inflammation is a provoke response to tissue injury
- It is a complex reaction of vascularised connective tissue to injury
- It is non-specific
- Aim = destory, dilute or “ward off” injurous angents
14
Q
Briefly outline the main difference between acute and chronic inflammation
A
Acute = short duration, rapid response, usually physiological
Chromic = long duration, slow response (often follwos acute inflammation), usually pathological
15
Q
What are the 5 clinical signs of acute inflammation?
A
- Rubour - redness
- Tumour - swelling
- Calor - heat
- Dolor - pain
- Functio laesa - loss of function
16
Q
What are some potential causes of acute inflammation?
A
- Physical agents (eg: trauma)
- Chemical agents (eg: poisons)
- Bacterial agents
- Immunological reactions
- Hypoxia
17
Q
What are the effects of acute inflammation?
A
- Fever
- Increased pulse + BP
- Increased temperature + chills
- Anorexia
- Leukocytosis
- Protein production (liver)
18
Q
What are the outcomes of acute inflammation?
A
- Complete resolution
- Healing with scar formation
- Chronic inflammation
- Abcess formation
19
Q
What three processes are invovled in acute inflammation?
A
- Vascular Changes
- Cellular Changes
- Chemical Mediators
20
Q
Outline the three major vascular changes that occur with acute inflammation
A
- Changes in vascular calibre
- Brief vasoconstriction (minimise spread)
- Prolonged vasodilation (increase blood flow to combat invaders)
- Physical = rubor + calor
- Changes in vascular permeability
- Increased permeability (plasma proteins + WBCs)
- Changes in blood flow
- Increased blood flow (accomodates emigraton of WBCs)
21
Q
What is the difference between (a) exudate and (b) transudate?
A
Exudate
- Inflammatory extra-vascular fluid
- Protein rich
- Result of inflammation
Transudate
- Ultra-filtrate of blood
- Low [protein]
- Result of hydrostatic or osmotic imbalance
22
Q
Extravasation of luekocytes (i.e. cellular events) is a co-ordinated event in acute inflammation - what steps are involved?
A
-
Margination
- WBCs come out of central axial column to the periphery
- WBCs align along the endothelial surface
-
Adhesion
- Activation of endothelial cells upreguates adhesion proteins
- Adhesion proteins enable WBCs to leave the vessel lumen
- Rolling
-
Diapediesis
- Leukocytes pierce the basement membrane and degrade it
-
Chemotaxis
- Locomotion oriented along a chemical gradient
- Assisted by chemo-attractants
-
Phagocytosis
- Recongition + Attachment
- Engulfment
- Killing + Degradation
23
Q
What 4 families of adhesion proteins are involved in acute inflammation?
A
- Selectins
- Immunoglobulins
- Integrins
- Mucin-like glycoproteins
24
Q
Outline the role of cytokines during the acute inflammatory process
A
Adhesin proteins are partially under the control of cytokines - they help to increase their affinity for endothelial binding sites, enabling stable binding between the endothelium and the WBCs (via the adhesin proteins)
25
What is the difference between a plasma-derived and cell-derived chemical mediator of acute inflammation?
Plasma-derived = synthesised in pre-cursor form, must be activate, short-lived
Cell-derived = synthesised de novo in active form, short-lived
26
Name and describe the two major vasoactive amines
**Histamine**
* Cell-derived
* Widely distributed
* Released in response to trauma and immune reactions
* Causes dilation of aterioles
**Serotonin**
* Cell-derived
* Present in platelets
* Simiar action to histamine
27
How is acute inflammation terminated?
Eradication of offending agent leads to the discontinuation of the inflammatory response
The process is aided by the short-lived nature of cells and chemicals invovled in inflammation
28
Define Chronic Inflammation
Chronic inflammation = _prolonged inflammation_ in which **active inflammation, tissue destruction + attempts at repair** are occuring simultaneous
29
Describe the two scenarios which can potentially result in chronic inflammation
1. Following acute inflammation
2. Low-grade, long-standing inflammatory resposne
30
List some of the potential causes of chronic inflammation
* Persistent infection (eg: TB)
* Prolonged exposure to toxins
* Autoimmunity
31
Name three histological features of chronic inflammation
* Infiltration by mononuclear cells (i.e. macrophages, lymphocytes, plasma cells)
* Tissue destruction
* Attempts at healing (i.e. connective tissue laying and fibrosis)
32
Name the 4 cell types invovled in chronic inflammation
* Macrophages
* Lymphocytes
* Eosinophils
* Mast Cells
33
Outline the role of macrophages in chronic inflammation
* Macrophages are the major cell type invovled
* There is macrophage accumulation in chronic inflammation
* Recruitment from blood via adhesion molecules
* Immobilisation of cells at inflammatory site (controlled by cytokines)
* Stimulation of cellular influx (macrophages attract cytokines etc.)
* This becomes unregulated in chronic inflammation leading to tissue damage
34
Define: granuloma
A granuloma is a focus of chronic inflammation consisting of an aggregate of macropahges which have been transformed into epitheloid cells surrounded by mononuclear leukocytes
35
Define: epitheloid cell
An epitheloid cell is a macrophage with an elongated appearance - they arise due to a pattern of chronic inflammation
36
Name and describe the three types of granuloma
* **Foreign body granuloma** - incite by relatively inert foreign bodies (eg: form around ruptured implants)
* **Immune granuloma** - caused by insoluble particles capable of inducing a cell-mediated immune respons (eg: TB)
* **Unknown aetiology** - eg: sarcoidosis
37
What is a **casseating granuloma**
A casseating (cheese-like) granuloma is typical of TB where the immun granuloma has started to necrose
38
What are the two types of cell injury?
Lethal = leads to cell death via necrosis or apoptosis
Non-lethal = degenerative changes that can be regenerated
39
Define degeneration
Degeneration = alteration or loss of struction and function in cells following injury or ageing
There are two types - pigmentation and non-pigmentation
40
What are the two major types of degenerative joint/bone disease?
Osteoarthritis & Rheumatoid arthritis - these are examples of non-pigment related degeneration.
They are assoiated with loss of function and pain due to the degeneration of structures
41
Give some examples of neurodegnerative diseases
Dementia & Parkinsons - these are both characterised by progressive, loss of function changes (i.e. neurodegenerative changes)
42
What are amyloids?
Amyloids are proteinaceous substances deposited in tissues that can cause amyloidosis (i.e. degeneration within the depostied structure)
43
List the (a) normal, (b) exogenous and (c) endogenous pigments involved in degeneration
(a) Normal
* Melanin
* Bilirubin
(b) Exogenous
* Carbon
* Tattoo
(c) Endogenous
* Lipofuscin
* Haemosiderin
* Melanin
44
Define: steatosis
Steatosis = abnormal accumulation of triglycerides within cells - it is an early indication of sress and injury
45
# Define the following:
(a) Tissue Repair
(b) Regeneration
(c) Healing
(a) Tissue Repair = replacement of lost/damaged tissue by regeneration and/or healing
(b) Regeneration = growth of cells and tissue to replace lost structures
(c) Healing = tissue response leading to the formation of scar tissue and/or fibrosis
46
Compare and contrast healing and regeneration
Healing
* Tissue response to injury
* Occurs in tissues unable to regenerate
* Involves repair and scarring
Regeneration
* Tissue response to lost structures
* Involves growth of cells
47
What is the difference between "true" and "functional" regeneration?
Treu Regeneration = occurs in labile tissues (eg: stem cells)
Functional Regeneration = occurs in stable/quiescent tissues (i.e. compensatory growth)
48
What pre-requisit is required for regeneration to take place?
Regeneration requires an intact connective tissue scaffold
49
Outline the process of true regeneration
* Regeneration involves the stimulation of division + migration of cells which induce replication
* Replication of cells restores function of damaged cells
* There can be de-differentiation of adult cells and secondary development to facilitate this
50
Outline the process of functional regeneration
Regeneration involves stimulation of the cell cycle to cause replication (this restores function)
51
What determines whether or not a tissue can be regenerated?
Its proliferative activity
52
Describe a labile tissue
* Continuously dividing cells
* Consist of lossely aggregated cells - these are highly susceptible to sublethal injury but readily regnerate
* Includes = skin, mucosa etc.
53
Describe a quiescent tissue
* Stable tissue
* Tissues have a complex structure of cells with high longevity
* Growth is a compensatory mechanism if any cells are damaged
* Includes = liver, kidney and pacreatic cells
54
What two factors help to stimulate cell replication (for regenerative purposes)?
**Growth Factors**
* Natrually occuring proteins capable of stimulating cell growth, proliferation + differentiation
* Function as ligands to stimulate secondary signalling pathways
**ECM**
* ECM surrounds cells
* Acts as a signal transducer
55
Define Scarring
Scarring = the healing of permentant tissues which are inacapable of regenerating - tissue will no longer function as before but is not in a damaged state
56
Describe a permenant tissue
* These are non-dividing tissues
* They are highly complex and cannot undergo any post-natal divisions
* Includes = cardiac cells and neurons
57
# Define the following growth disorders:
(a) Hyperplasia
(b) Hypertrophy
(c) Metaplasia
(d) Dysplasia
* Hyperplasia = increase in cell number without structural change
* Hypertrophy = increase in cell size within an organ
* Metaplasia = change from one cell to to another
* Dysplasia = disordered cell growth with loss of uniformity
58
What is a **neoplasm**
A neoplasm = abnormal and autonomous cell growth
* Growth exceeds surrounding tissues
* Growth is uncoordinated
* Can either be benign or malingnant
* aka - tumour
59
What are the 4 main causes of epithelial dysplasia?
* Infection
* Inflammation
* Environmental, physical & chemical factors
* Genetics
60
What are the implications of dysplasia
* Irreversible changes to the cell
* Cancer (some changes are carcinogenic)
61
Name some common sites of dysplasia
**Squamous Cells **
* Cervix
* Oesophagus
* Skin
* Lungs
**Glandular Cells **
* Cervix
* Uterus
* Bowel/colon
* Breast
* Liver
62
Outline the microscopic features of dysplasia
* Atypia (loss of normal cellular appearance)
* Cytomegaly
* Anarchy (loss of cellular polarity)
* Nuclear atypia
* Nucleomegaly
* Loss of maturation
63
Outline the pathogenesis of dysplasia
* Recovery and regeneration over time leds to changes in cell morphology
* Dysplasia is a type of cellular adaptation
* Begins with hyperplasia
* Then carcinoma in situ
* Finally, invasive cancer
64
Outline the adenoma-carcinoma sequence
* Cancers develop from multiple sequential mutations in a step-wise manner
* Adenoma-carcinoma sequence is in colon cancers
* The colon can undergo 4 mutations before carcinoma sets in
* Normal --\> Adenoma --\> Dysplasia --\> Carcinoma
65
What are normal physiological levels of calcium?
2.2-2.6 nM
66
99% of the body's calcium is within the bone, however, 1% is circulating - outline some of the key roles of circulating calcium
Normal nerve & muscle function
67
Outline the role of PTH in the regulation of calcium
* PTH = parathyroid hormone
* Regulates calcium by negative feedback
* Low calcium = high PTH
68
In terms of calcium regulation - what does PTH cause?
* Movement of calcium from the bone - increases free calcium levels in the blood
* Activation of renal 1-a-hydroxylase - activates Vit. D to increase calcium absorption
* Phosphate loss - increasing calcium absorption causes phosphate losses
69
What are the major sources of Vit. D?
* Vit. D3 = active vitamin, synthesised by the skin
* Vit. D2 = active vitamin, found in plants
70
Where is Vit. D processed?
Following ingestion (or absorption), Vit. D is hydroxylated by **_25-hydroylase_** in the *liver*
(this is inactive, stored Vit. D)
71
How is Vit. D activated?
Activation of 25-hyroxy-Vit. D (i.e. from liver) occurs in the _kidneys_ via **_1-a-hydroyxylase_**
This is under the control of PTH (and is rate-limiting)
72
In reference to calcium, what is the role of Vit. D?
Vit. D controls the absorption of calcium from the small intestine (this is under the control of PTH)
73
List some common conditions affecting calcium
* **Primary hyperparathyroidism**
* ****High Ca, High PTH, Low PO
* **Osteoporosis**
* ****Less bone, normal composistion
* **Osteomalacia**
* ****Same bone amount, abnormal composition
* **Vit. D deficiency**
* ****Paediatric = rickets
* Causes secondary hyperparathyroidism
* **Paget's disease (of the bone)**
* ****High alkaline phosphatase, normal Ca
* **Cancer w/ bone mets. **
* ****PTHRP release
* Hypercalcaemia
74
What is secondary hyperparathyroidism?
Low Vit. D = Low Ca = Secondary Hyperparathyroidism
* Bones are continually releasing calcium stored due to low Vit. D = Low Ca
* Bones become weaker
* Rx = Vit. D + Ca
75
Describe the clinical signs of low calcium levels
(hypocalcaemia = secondary hyperparathyroidism)
* Tetany - intense muscle spasm (esp. in carpal mucles)
* Alkalotic - presents as hyperventilation
* Hypocalcaemic = calcium bound to albumin (can be tested via trousseau's sign)
* Trousseau's Sign - arm spasms upon constriction
76
Describe the biochemistry seen with hyperparathyroidism (secondary)
Secondary hyperparathyroidism = hypocalcaemia
* Low Ca
* Low PO
* High PTH
* High Alkaline phosphatase
77
What are the two causes of hypercalcaemia
**Malignancy**
* Cancer w/ bone metastases
**Primary Hyperparathyroidism**
* Benign tumour of PTH --\> increases in PTH --\> increases in Ca
78
What is the clinical presentation of prmary hyperparathyroidism?
* *Bones* - calcium out of bones = fractures
* *Stones* - high circulating calcium = kidney stones
* *Moans* - psychiatric symptoms
* *Groans* - high calcium = constipation + abdo pain
79
Briefly describe osteoporosis
* **Less bone, normal structure**
* One of the major metallic bone diseases
* A type of degenerative bone disease
* Commonly found in post-menopausal women (due to low oestrogen)
* _Caused by hypocalcaemia _
* Results in multiple pathological fractures and loss of bone mass
80
Briefly describe osteomalacia
* **Same amount of bone, abnormal structure**
* One of the major metallic bone diseases
* A type of degenerative bone disease
* _Caused by lack of Vit. D_
* Results in demineralisation of bone
* Commonly found in:
* Renal Px (no active Vit. D)
* Rickets (lack of Vit. D)
* Indian population (phytic acid = 24-hydroxy = inactivates Vit. D)
81
Briefly describe Paget's disease of the bone
* Rare degenerative condition
* Causes _constant bone regeneration_
* Increased bone turnover but to high alkaline phosphatase
82
What is PTHRP
PTHRP = parathyroid related protein
* Physiological - expressed during pregnancy and lactation to release calcium enabling foetal bones to grow
* Pathological - cancer causes bones to degenerate
