Pathology/Histopathology Flashcards
1
Q
What is neoplasia?
A
Neoplasia refers to “new growth” as an
abnormal growth of tissue which, if it forms a
mass, is commonly referred to as a tumor.
Prior to the abnormal growth of tissue, as
neoplasia, cells often undergo an abnormal
pattern of growth, such as metaplasia or
dysplasia. However, metaplasia or dysplasia
does not always progress to neoplasia.
2
Q
What occurs in hypertrophy, hyperplasia, atrophy, metaplasia, dysplasia
A
Hypertrophy – ⇑ cell & tissue size
Hyperplasia – ⇑ cell numbers (cell division)
Atrophy – decrease in cell size, numbers
(cell death), tissue size
Metaplasia – change in cell differentiation,
better equipped for environmental stress
Dysplasia – distorted growth pattern, preneoplastic,
often increased mitoses (may be
considered abnormal hyperplasia). May not be
reversible.
3
Q
What does disease development depend on?
A
• Cause and its duration and severity • Cell type, stage of cell cycle, and cell adaptability (consider heart, brain, versus skin, liver) • Disease changes occur only after critical cellular, biochemical and molecular damage
4
Q
What are the three cell types?
A
Labile – Continuous cell proliferation (skin, gut,
respiratory tract, bone marrow, seminiferous
tubules in testis, lymph nodes). Particular risk of
cancer and radiation damage.
Stable – Do not normally proliferate (adult),
but are able to undergo cell proliferation (liver,
kidney, smooth muscle)
Permanent – No (or little) capacity to divide in
adult tissue (neurons, cardiac muscle)
5
Q
What does steatosis/fatty liver show histologically
A
Large circular cellular inclusions as lipids
6
Q
What is apoptosis vs necrosis?
A
Necrosis occurs when cells are irreversibly damaged
by an external trauma. The cells lose energy, plasma
membrane pumps stop working, cells fill with water
and essentially explode.
Apoptosis is thought to be a physiological form of
cell death whereby a cell provokes its own demise
(commits suicide) in response to a stimulus. Cells
shrink, bud, and are phagocytosed (macrophages but
also adjacent cells).
7
Q
What are the aims of inflammation?
A
Wall off, remove, dilute and start process of healing
Occurs in vascularized tissue, fluid, protein and leucocytes diffuse out
8
Q
What happens in fibrosis?
A
Thickening and scarring of connective tissue, rebuilding of ECM with collagen
9
Q
What happens in acute appendicitis?
A
Mucosal ulceration pus within meso-appendix
10
Q
What are the general signs of acute inflammation?
A
Heat – because of local reaction Redness – blood slows because vessels dilate Swelling – fluids leak from vessels to dilute the damage Pain and loss of function – this allows time to heal
11
Q
What are the systemic signs of acute inflammation?
A
Fever (pyrogens – good or bad) Leukocytosis (↑ leukocyte count – leucocytes are white blood cells) Acute phase proteins Acute phase reactions such as sleepiness, hypotension
12
Q
What happens in acute inflammation
A
- CHANGES IN BLOOD VESSELS
- INCREASED FLUID FROM VESSELS
- INCREASED LEUCOCYTES
(NEUTROPHILS, LYMPHOCYTES) IN
INFLAMED AREA
13
Q
What is chemotaxis?
A
Chemical substances (chemokines, cytokines)
are released at the site of injury.
These are responsible for the vessel and
cellular changes of acute inflammation.
Chemotaxis leads to movement of inflammatory
cells via a chemical gradient. Concentration of
the chemo-attractant is highest near the
injury.
14
Q
What happens in meningitis/laryngitis?
A
Meningitis: viral/bacterial infection in meninges, inflammatory response, oedema. Oedema causes increased pressure. This in turn causes headache, etc. Inflamed (dilated) meningeal blood vessels become occluded. Haemorrhagic infarction of associated brain occurs. Laryngitis: viral/bacterial infection, inflammatory response, oedema, airway obstruction
15
Q
Why does tuberculosis initiate a chronic response straight away?
A
Neutrophils are inneffective at removing the virus
16
Q
What is pulmonary fibrosis?
A
Coal worker’s pneumoconiosis (CWP)
“Black lung disease”
Inflammation of the lungs, often leading to fibrosis
that is caused by breathing a high concentration of
coal dust (or mixed dust) particles.
17
Q
How does fibrosis occur?
A
Consists of:
Proliferation of activated macrophages
Activated fibroblasts (myofibroblasts)
New vessels
Collagen and other ECM proteins in area of
damage.
On surface of wound, pink granular appearance.
18
Q
What is 1st or 2nd intention healing?
A
Primary Intention Healing – This occurs where the tissue surfaces have been approximated (closed). This can be with stitches, or staples, or skin glue (like Derma bond), or even with tapes (like steri-strips). This kind of closure is used when there has been very little tissue loss. It is also called “primary union” or “first intention healing.” An example of wound healing by primary intention is a surgical incision.
Second Intention Healing – A wound that is extensive and involves considerable tissue loss, and in which the edges cannot be brought together heals in this manner. This is how pressure ulcers heal. Secondary intention healing differs from primary intention healing in three ways:
The repair time is longer.
The scarring is greater.
The chances of infection are far greater
19
Q
What are the factors that influence healing?
A
Nutrition, age, adequate blood supply
(atherosclerosis), disease (diabetes), hormones
(glucocorticoids).
Infection, mechanical factors (movement around
wounds), foreign bodies (sutures, glass,
splinters), size and location (small cut vs blunt
trauma)
Inadequate healing leads to rupture and/or
ulceration.
Excessive healing leads to mounds of collagen
called keloids (hypertrophic scar)
20
Q
What is the differences between atherosclerosis, atheroma and aneurism?
A
ATHEROSCLEROSIS = PROCESS OF CHANGES (LIPID, CARBOHYDRATE, CALCIUM ETC) IN INTIMA OF ARTERY ATHEROMA = ATHEROSCLEROTIC PLAQUE IN AN ARTERY ANEURISM = ABNORMAL WIDENING OR BALLOONING IN AN ARTERY WALL, CAUSING WEAKENING
21
Q
What happens in atherosclerosis?
A
Macrophages arrive to break up cholestrol
Necrosis occurs
Artery wall becomes hard due to calcification
22
Q
What does Oil red O do?
A
stain to show lipids in vessel wall in atherosclerosis
23
Q
What is an atheroma?
A
An atheroma is a reversible accumulation of degenerative material in the intimal layer of an artery wall. The material consists of mostly macrophage cells and debris containing lipids, calcium and a variable amount of fibrous connective tissue.
24
Q
What is an aneurism?
A
An abnormal, localised, dilatation of an artery
25
What are the different types of aneurism?
Saccular- bulge on the artery
Fusiform
Dissecting
26
What is a thrombosis?
The formation or presence of a blood clot in a blood
vessel. The vessel may be any vein or artery. The clot
itself is termed a thrombus.
27
What are the symptoms of deep vein thrombosis?
Pain and tenderness in the leg
Pain on extending the foot
Swelling of the lower leg, ankle and foot
The skin is red and warm.
28
What is virchows triad?
Endothelial injury
<> abnormal blood flow
>Hypercoagulability
> all lead to thrombosis, however endothelial injury is the main reason, the others are factors that lead to it
29
What is a thrombus?
a clot of blood formed
| during life within the heart or blood vessels
30
What is an embolus?
a bit of foreign matter in the
blood stream – like a blood clot (thrombus), air
bubble, cancer cells, fat, cardiac vegetations
31
What can a thrombus lead to?
Lysis and resolution
Organisation
Recanalisation
Embolism
32
What is the most common site of occlusion in the heart?
LAD coronary artery
33
What is an ischeamia vs infarct?
```
ISCHAEMIA (is-kem’ia)
An inadequate blood supply to an organ
or part of the body, especially the heart
muscles.
INFARCT
Small localised area of necrosis usually
resulting from failure of blood supply.
```
34
What is shown on the histology of a myocardial infarct
• Infarcted necrotic area surrounded by cardiac
muscle fibres that are intensely stained by eosin
(eosinophilic) when compared to normal
myocardial fibres.
• Separation of the myocytes by oedema.
• Heavy infiltration of the damaged myocardium
by neutrophils. At this stage, there is no
granulation tissue formation (which would have
come later should the patient have survived)
35
What are the coomplications of a MI?
• Arrhythmias due to electro conductive tissues like
“bundle branches” dying and being replaced with
non-conductive scar tissue
Bundle branches play an integral role in electrical
conduction in the heart by transmitting cardiac action
potentials from bundle of His to Purkinje fibres
• Aneurisms of the ventricle due to weakness and
dilatation of the muscular wall
36
What is the difference between aortic valve stenosis and insufficiency?
Aortic valve stenosis is narrowing of the aortic
valve, which normally allows blood to flow from
the left ventricular chamber into the aorta and to
the body. Stenosis prevents the valve from
opening properly. The heart works harder to pump
blood through the valve.
Aortic valve insufficiency, also known as aortic
regurgitation, is the leaking of the aortic valve of
the heart that causes blood to flow in the reverse
direction during ventricular diastole, from the
aorta into the left ventricle.
37
What is valvular heart disease?
```
Damage to or a defect in one of the
four heart valves: the mitral, aortic,
tricuspid or pulmonary.
The mitral and tricuspid valves
control the flow of blood between
the atria and the ventricles (the
upper and lower chambers of the
heart).
```
38
What happens in heart failure?
Inability of the heart to keep up with the demands on it
and, specifically, failure of the heart to pump blood with
normal efficiency.
Left: pulmnary congestion
Right: systemic venous presusre increase
39
What is an oedema?
```
OEDEMA = increase in the amount
of fluid in the interstitial spaces (e.g.
connective tissue), free spaces in
tissue (e.g. pulmonary alveoli), and
body cavities (e.g. pleural, pericardial
or abdominal).
```
40
What does nutmeg liver result from?
Right sided heart failure
41
What are the defence mechanisms against pulmonary disease?
```
• Physical
1. Filtering within
the upper airways.
2. Reflexes
including coughing
3. Muco-ciliary
escalator
• Cellular
1. Alveolar
phagocytic
inflammatory cells
2. Alveolar
immunologic
mechanisms inc.
IgA
```
42
What is pneumonia vs abscess?
Pneumonia: lung inflammation caused by bacterial or
viral infection, in which the air sacs fill with pus and
may become solid. Inflammation may affect all lung
tissue (bronchopneumonia) or only one lobe (lobar
pneumonia).
Abscess: a localized collection of pus within the
tissues of the body, often accompanied by swelling
and inflammation (heat, redness, swelling, oedema)
and frequently caused by bacteria.
43
What is the most common bacteria causing pneumonia?
Streptococcus pneumoniae
44
What is the difference between Broncho and Lobar pneumonia
```
Broncho
• Common
• Often an extension of
bronchitis
• Opportunistic infections
affecting the old, young,
immuno-compromised
• May become confluent &
then hard to distinguish
from lobar pneumonia
```
```
Lobar
• Rare due to
antibiotics however
resistant strains are
problematic
• Highly virulent
bacterial infection
that can infect even
the most healthy of
individuals.
```
45
What are the complications of bacterial infections?
Some types of bacteria lead to necrosis – this
may form an abscess
Empyema – infection spreads to pleural cavity
Organisation of exudate – lung solidifies
Dissemination of infection – heart valves,
pericardium, brain, kidneys, spleen, joints.
46
What is an abscess?
Abscess = local
inflammation
within an organ
47
What causes pulmonary embolism?
• Pulmonary embolism is caused by a travelling blood clot
• In most cases, a blood clot (thrombus) in the leg breaks loose
and travels to the lungs.
• The origin of the embolus is usually deep vein thrombosis.
48
What develops histologically with pulmonary embolus
Granuloma
49
What is chronic bronchitis and its pathologY?
```
“persistent cough with sputum
production for at least three months
in two consecutive years”
PATHOLOGY:
In large airways; increased thickness
of the mucous gland layer; increase in
secretion from goblet cells; reduced
number of ciliated cells
```
50
What is brnchiolitis?
Bronchiolitis: Inflammation of the fine bronchioles,
rather than the bronchi.
• Large quantity viscid (thick and yellow)
sputum (mucoid OR purulent and infected),
earliest and major pathological feature
• Permanent dilatation of air spaces distal to
terminal bronchioles due to destruction of
their walls without fibrosis
• Heart failure, as the heart has to work that
much harder to pump blood through the
damaged lungs
51
What is emphysema?
Abnormal permanent enlargement of air spaces,
distal to the terminal bronchioles, accompanied
by destruction of their walls.
Effective obstruction or block to air being
exhaled ie. loss of elastic recoil of lung
52
What is emphysema vs bronchitis?
Emphysema- walls of alveoli are damaged by inflammation. ALveoli can lose elasticity, become overstretched and rupture
Bronchitis- chronic inflammation + thickening of walls of broncial tubes which narrows them
53
What are the causes of emphysema?
Commonly cigarette smoke in small bronchi and
bronchioles. Also other pollutants.
Hereditary deficiencies of anti-elastases
Increase in inflammatory cells. Release of
enzymes eg. proteases, elastases which digest
elastic tissue in the lung.
Anti-elastases normally inactivate elastases but
cigarette smoke can inactivate these.
54
What are the symptoms of emphysema?
• Breathlessness, person may also wheeze or
have a cough
• Weight loss, energy directed towards the work
of breathing
• Heart failure, particularly of the right
ventricle
• Respiratory failure, not enough functioning lung
•Coma, not enough oxygen to brain
•Lung collapse (pneumothorax) after rupture of
bullae, fatal.
55
What is bronchiectasis?
```
Chronic destructive infection of bronchi
and bronchioles, abnormal dilatation of
the larger airways – including the bronchi,
together with the larger of the
bronchioles. Usually permanent.
Chronic cough and a lot of sputum
production.
```
56
What is pneumoconiosis?
Inflammation of the lungs, often leading to
fibrosis that is caused by breathing a high
concentration of coal dust (or mixed dust)
particles. Compare with “asbestosis”.
57
What is asbestosis?
Asbestosis = chronic inflammatory condition
Pulmonary fibrosis is an outcome
Fine particles of asbestos (as in asbestos mining) are
inhaled. The lung tissue becomes scarred over time.
Asbestosis seems to have the same mechanism/s as
mesothelioma (cancer of pleural lining) and other
asbestos-related cancers ie. Stimulation by cytokines.
58
What is IBD, Ulcerative colitis and Crohns disease?
• IBD = umbrella term for disorders that involve
chronic inflammation of the digestive tract.
• Ulcerative colitis - long-lasting inflammation and
sores (ulcers) in the innermost lining of the large
intestine (colon) and rectum.
• Crohn’s (or Crohn) Disease - indeterminate colitis,
characterized by inflammation of the lining of the
digestive tract, and often spreading deep into
affected tissues (transmural).
59
What are the symptoms of IBD?
```
• IBD symptoms vary, depending on severity
of inflammation and where it occurs.
• Diarrhoea
• Fever and fatigue
• Abdominal pain and cramping
• Blood in stool
• Reduced appetite
• Unintended weight loss
```
60
What is the difference Chrons vs Ulcerative colitis gross pathology
Skip lesions in crohns disease, no skip lesion in ulcerative colitis
61
What is a granuloma?
Granuloma - a body/structure with a granular look, histologically
They are a collection of immune/phagocytic cells (macrophages,
here called epithelioid cells), fibrous tissue and lymphocytes.
Granulomas form in many chronic inflammatory conditions.
There is overactivity of the immune system as it attempts to wall
off substances it perceives as foreign but is unable to eliminate.
Necrotizing granulomas have a necrotic core (typically in TB).
62
What is the pathology/histopathology of ulcerative collitis?
Inflammation is limited to mucosal layer of colon, rectal layer is involved with inflammation
Granulomas
63
Complications and causes of diverticulitis?
• Diverticulum (pl. diverticula): Small bulging
sac pushing outward from the colon wall.
With aging, pressure within large intestine
(colon) causes pockets of tissue (sacs) to
push out from the colon walls. Diverticula can
occur throughout colon but are most common
near the end of the left side of the colon,
the sigmoid colon
• Diverticulitis = infection and inflammation of
the diverticulum. Chronic diverticulitis,
inflammation and infection may subside, but
they may never clear up completely.
• Inflammation of diverticulitis can result in
bowel obstruction, constipation, thin stools,
diarrhoea, abdominal swelling or bloating, and
abdominal pain.
64
What is an inguinal hernia?
• A hernia is a condition in which part of an organ is
displaced and protrudes through the wall of the
cavity containing it (often involving the intestine at a
weak point in the abdominal wall).
• Inguinal hernias are relatively common in the elderly
with an estimated prevalence 6%. Incarceration
(trapping) of an inguinal hernia can lead to intestinal
obstruction, strangulation and infarction.
65
What is an infarct?
```
• An infarct is caused by obstruction of
the blood supply to an organ or region of
tissue causing local death (necrosis) of
the tissue
• Obstruction can be mechanical (eg.
herniation) or a thrombus/embolus
```
66
What is mesentric thromboembolism?
• Mesenteric venous thrombosis is a blood clot in one or more
of the major veins that drain blood from the intestine
• Thromboembolism simply refers to the embolism that forms
from this blood clot.
67
What is barret osophagus?
• Barrett esophagus: Gastric or intestinal type of
mucosa lines distal oesophagus above lower
oesophageal sphincter. This has altered structure
(taller). Mostly acquired & in adults, but may be
seen in children, and rarely congenital in origin.
68
What are the complications of long standing refulx?
• Complication of long-standing reflux leading to
inflammation and ulceration of squamous mucosa,
followed by healing by re-epithelialization &
ingrowth of pluripotent stem cells which
differentiate into gastric or intestinal epithelium.
69
What are polyps?
Colonic polyps - extra tissue growing in the
| colon that can become cancerous
70
What happens in colon adenocarcinoma?
```
Most derived from benign adenoma (polyp)
which undergoes malignant
transformation.
GROWTH: exophytic lesions growing along
one side of the bowel wall (more common
in the right side) or annular, constricting
tumours (napkin ring tumours in distal
colon and rectum).
```
71
What is the histological appearance of adenocarcinoma?
```
• Invasion into the muscularis externa
and into peritoneum.
• Abnormal cells are pleiomorphic in their
size, shape and nuclear features
• The nuclei are hyperchromatic and
pleiomorphic with large nucleoli
```
72
What is appendicitis?
```
Appendicitis occurs
when appendix is
blocked, often by
stool, foreign body,
or cancer. Blockage
may also occur
from infection
-
the appendix may
swell in response to
infection in any
part of the body.
Obstruction of
lumen of appendix
present in up to
80% cases of acute
appendicitis.
```
Faecolith- stone of faeces
73
How does appendicitis appear histologically?
Transmural inflammation
Fibrin and pus on serosal surface
Lymphoid follicles
74
How is appendicitis treated? What can happen post surgery?
Appendicitis is typically treated with an
appendectomy.
Following abdominal surgery, adhesions (scar
tissue) may form and may cause a subsequent
small bowel obstruction.
75
What is pancreatitis? (Causes, features, complications)
Pancreas produces enzymes that help digestion
(exocrine pancreas) and hormones that help regulate
the way your body processes sugar (glucose
metabolism) (endocrine pancreas).
Inflammation of the pancreas. Acute pancreatitis —
appears suddenly and lasts for days. Chronic
pancreatitis - occurs over many years with fibrosis.
Mild cases of pancreatitis may resolve without
treatment, but severe cases can be life-threatening.
76
What are the symptoms of acute hemorrhagic pancreatitis? What are the causes?
severe epigastric pain and nausea.
gallstones in the bile duct,
alcoholism, trauma, immune conditions
77
What happens microscopically in pancreatitis?
areas of calcification and enzymatic fat
necrosis
Acinar cell necrosis releases digestive
enzymes which cause further injury including
“fat necrosis” of fat adjacent to pancreas.
78
What are the complications of pancreatitis?
Complications include retroperitoneal haemorrhage
| (*), diabetes, pseudocyst formation, organ failure and shock.
79
How does pancreatic atrophy and fibrosis occur?
distal duct obstruction (eg. gallstone or
proteinaceous secretions) leading to proximal
dilatation of the ductal system and backpressure
leading to loss of acinar elements via apoptosis
and/or necrosis, with inflammation and fibrosis.
80
What is liver Cirrhosis?
• These specimens show Cirrhosis, which is an irreversible injury to the
Liver. Cirrhotic livers tend to be smaller than normal due to the
replacement of functional hepatocytes with non-functional fibrotic
areas and regenerative nodules (*).
81
What are the causes and complications of cirrhosis?
• Severe alcoholism
• Viral Hepatitis infection
• Obesity causing steatosis (fatty liver)
• Various genetic conditions (Hemochromatosis and
Primary Biliary Cirrhosis/Primary Sclerosing
Cholangitis).
Complications include
• Bleeding oesophageal varices (due to portal venous
congestion); splenomegaly (enlarged spleen); ascites
(fluid in the abdomen); hepatic encephalopathy
(confusion due to build up of ammonia); kidney
failure; hemorrhoids;and the development of primary
liver cancer (Hepatocellular Carcinoma or HCC).
82
What is metastasis?
Metastasis = movement of cancer from site of original
| cancer to a new and different site
83
What are the common routes of metastasis?
1. Local invasion of tissue spaces
2. Infiltration of lymphatics (most common)
3. Vascular spread – usually veins, venules,
capillaries, sometimes arteries
4. Seeding of body cavities, eg. abdominal,
cerebro-spinal spaces
5. Epithelial-lined cavities and ducts eg ureter,
Fallopian tubes
6. Surgery
84
Where is kidney disease localised?
Glomeruli, tubules, interstitium, blood vessels
85
What can happen in kidney failure?
• Blood is not cleansed – toxic contents build
• Fluid balance is no longer automatic. YOU
have to watch what you eat and drink
• Hypertension is common in people with kidney
failure – it is both a cause and complication of
kidney failure
• Without healthy red blood cells you become
anaemic
• Calcium and phosphate imbalance; kidney
disease-associated bone disease
86
What is hypertensive kidney?
Hypertension is an outcome, and a
contributing factor, to chronic kidney disease
(CKD).
Significant atrophy
Glomerulosclerosis
87
What is acute kidney injury?
```
• Sudden deterioration of renal function
due to destruction of tubules of
nephrons
• Usually due to an acute ischemic or
toxic event (causes an “acute tubular
necrosis” or “acute kidney injury”)
– Stenosis, trauma, nephrotoxic antibiotics
(cyclosporin, amphotericin), heavy metals,
myoglobinuria, x-ray contrast dye,
aminoglycosides, multiple myeloma
```
88
How do you characterise acute renal failure functionally and structurally?
Functionally:
• fall in glomerular filtration rate (GFR)
• low or little urine
• increased levels of nitrogenous wastes in the blood,
primarily urea (BUN) and creatinine (SCr)
Structurally (histopathology)
• by cell death (apoptosis and necrosis)
• loss of cell adhesion in intrinsic renal cell
populations, in particular the renal tubular epithelium
89
Why is there less glomerular filtration in aute renal failure?
```
Vascular
• Endothelial
dysfunction
• Vasoconstriction
• Vasodilatation
• Adhesion of acute
inflammatory cells
Tubular
• Cytoskeletal injury
• Necrosis/Apoptosis/
sublethal injury
• Cell loss
• Obstruction
• Backleak of urine
```
90
What is post kidney acute kidney disease?
Blockage to urine flow at ureter, bladder or urethra
Distention of renal pelvis and calyces due to urine accumulation. Cause of
disease is physical obstruction of urine outflow.
91
What happens in kidney + urinary tract infections?
Depending of the extent of injury, this may
leave scarring. Symptoms include fever and
flank tenderness.
92
What is leiomyoma?
is a benign tumour of the uterine smooth
muscle cells, or the myometrium (leio = smooth;
myo = muscle) . Sometimes called a fibroid.
Common cause of uterine bleeding and pain.
Present in approximately 25% of women of
during their reproductive lives.
Leiomyomas, even though benign, may become
malignant (leiomyosarcoma) and very rarely
metastasise, predominantly to the lungs.
