Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Medicine year 1 semester 2 > Case 10- Gallbladder and Pancreas pathology > Flashcards

Case 10- Gallbladder and Pancreas pathology Flashcards

1
Q

Causes of bile duct obstruction

A
  • Gallstones
  • Strictures (narrowing due to scarring) due to inflammation or previous surgery
  • Tumours either primary or secondary from the pancreas.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Bile duct tumours

A

• Benign: rare intraductal papillary tumours.
• Malignant: similar to hilar cholangiocarcinoma.
You can have proximal CBD carcinoma and distal CBD carcinoma. Can occur at any point in the bile duct from gallbladder to pancreas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Risk factors for Gallstones

A

Female. obesity, age, pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Gallstones

A

Stones formed within the gallbladder, made from bile components
10-20% of the population are affected
75% are asymptomatic
Can block the cystic duct, causing pain i.e. biliary colic
Feel it in the right upper quadrant
Worsens after meals
Can remove the gallbladder if they are very bad

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cholecystitis

A

Inflammation of the gallbladder
90% gallstone related
Can be chronic due to repeated mechanical trauma from stones
Can be acute when a stone compresses the blood supply to the gallbladder. Presents with signs of infection. Positive Murphy sign i.e. patient stops inhalation during a deep breath due to pain when pushing on the right side of their abdomen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Cholangitis

A

Inflammation of the bile duct. Often occurs due to gallstones being lodged there. Can lead to inflammation in the Pancreas and biliary system. Can lead to Pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Gallbladder carcinoma

A

Relatively rare. 80% are due to chronic cholecystisis/gallstones. It has no symptoms till very late stage. Late stage symptoms are jaundice, vomiting, weight loss and abdominal pain. More common in females and at an older age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Pathology of gallbladder carcinoma

A

Thickened gallbladder wall, gland forming tumour with mucin production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Pancreatic ductal adenocarcinoma

A

Occurs in glands which produce mucus. Very aggressive cancer with a high mortality rate. The most common type of Pancreatic cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Risk factors for Pancreatic ductal adenocarcinoma

A

Smoking, type 2 diabetes, chronic pancreatitis and family history

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Clinical presentation of Pancreatic ductal adenocarcinoma

A

Late symptoms, the majority (85%) are inoperable at presentation. Symptoms only occur when the bile duct is obstructed. The patient tends to die shortly after the cancer is identified. There will be abdominal or back pain, jaundice and weight loss. You may also get diabetes mellitus, nausea/vomiting, poor appetite and thromboses in the leg (Trousseau’s sign).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pathology of Pancreatic ductal adenocarcinoma

A

An ill defined, infiltrative, firm fibrous tumour which normally occurs in the head of the pancreas. Under a microscope you see abnormal glands associated with prominent stroma (fibrous tissue).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pancreatic neuroendocrine tumours (PanNETs)

A

Rare tumours that arise from endocrine cells, such as the islets of langerans. They are mostly well differentiated, potentially malignant with slow progression. The tumours can still produce specific hormones. Insulinoma is a tumour that produces Insulin. The tumours can be part of an inherited syndrome with multiple tumours. Tumours that are poorly differentiated are rare and highly aggressive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pathology of Pancreatic neuroendocrine tumours

A

Well circumscribed. Soft, solid and tan. Can be cystic. They have an ‘Oraganoid’ architectural pattern which is commonly nested or trabecular.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Pancreatitis

A

Inflammation of the pancreas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Causes of Pancreatitis

A

50% of cases and related to Gallstones and 30% of cases are related to alcohol. The gallstones cause backflow of bile into the gallbladder. Other causes include trauma, ERCP (investigations of the biliary tree), drugs, infections (mumps, AIDs), hypothermia and vascular causes (i.e. shock).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Symptoms of acute Pancreatitis

A

Sudden severe abdominal pain, radiating to the back. Associated with nausea and vomiting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Definition of acute Pancreatitis

A
  • Characteristic pain
  • Serum amylase or lipase levels three or more times the normal amount
  • Characteristic imaging (CT or MRI)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Pathology of acute pancreatitis

A

Enzymes are prematurely activated
Causing pancreatic tissue destruction
Can be due to direct injury of acinar cells / duct obstruction
Enzymes cause leaky vessel - oedema and inflammation
Fat necrosis due to lipolytic enzymes
Can lead to haemorrhage due to destruction of blood vessels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Mild acute Pancreatitis

A

Interstitial oedematous pancreatitis
No necrosis
Resolves within 1 week
Length of organ dysfunction / systemic inflammatory response less than 2 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Moderate acute Pancreatitis

A 
Organ dysfunction also less than 2 days
Some further complications
Sterile/ infected acute peripancreatic fluid collection can lead to sepsis
Pseudocysts will form
Fluid collection but no necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Severe acute Pancreatitis

A

Necrotising pancreatitis
Affects 5-10% patients
Organ dysfunction lasts more than 2 days
Medical emergency due to collection of infected / sterile acute necrotic collection
Can cause multi-organ failure
Extensive bruising of the flanks i.e. Grey Turner’s sign

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Chronic Pancreatitis

A

There is continuing inflammation with exocrine atrophy and fibrosis. 60-80% male patients, rarer then acute pancreatitis. Tend to be younger than those with acute pancreatitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Chronic Pancreatitis causes

A

Smoking, long term alcohol excess, hereditary/autoimmune pancreatitis. Can also be caused by conditions that obstruct the Pancreatic duct like inflammation, tumour, gallstones and congenital malformations (i.e. pancreas divisum)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Clinical presentation of Chronic Pancreatitis

A

Malabsorption
Steatorrhea
Diabetes
Intermittent upper abdominal pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Pathology of chronic Pancreatitis

A

Increased pancreatic juice
Dilated pancreatic duct become filled with protein plugs which undergo calcificatiom
Occlusion of pancreatic ducts - back flow of acinar juice
Leading to acinar atrophy and fibrosis

27
Q

Complications of acute Pancreatitis

A
  • Pseudocysts: fluid surrounded by fibrosis.
  • Necrotic collections and infection.
  • Bleeding
  • Shock
  • Chronic pancreatitis
28
Q

Complications of chronic Pancreatitis

A
  • Pseudocysts (fluid surrounded by fibrosis).
  • Diabetes
  • Pancreatic ductal adenocarcinoma.
29
Q

Cardinal symptoms of Pancreatic disease

A
  • Pain- radiating to the back, severe in pancreatitis.
  • Diabetes- from pancreatic cancer and chronic pancreatitis.
  • Weight loss
  • Chronic fatigue
  • Shock- from acute pancreatitis
  • Fever
  • Nausea, vomiting and loss of appetite
  • Dark urine and pale faeces- pancreatic cancer with obstruction of the common bile duct
  • Jaundice-pancreatic cancer with obstruction of the common bile duct
30
Q

Cardinal symptoms of Gallbladder disease

A
  • Pain- in the right upper quadrant radiates to the shoulder. Biliary colic (colicky pain) especially after a fatty meal
  • Jaundice- if gallstones in duct
  • Dark urine, pale faeces- if gallstones in duct
  • Fever
  • Nausea, vomiting
  • Heartburn, indigestion, excessive gas
  • Tenderness in right upper quadrant
31
Q

Xenograft

A

Transplantation between different species i.e. a pig heart

32
Q

Autograft

A

Transplantation from one part of the body to another part of the body within the same individual

33
Q

Allograft

A

Transplantation between non-genetically identical members of the same species. This is the most common type of transplant surgery and requires blood group, tissue type and organ size matching.

34
Q

MHC

A

Major histocompatibility (MHC) complexes are cell surface protein complexes that enable T lymphocytes to identify non-self/foreign invaders. There are two types MHC class 1 and MHC class 2.

35
Q

MHC class 1

A

Present on the membrane of all nucleated cells. It differentiates self from non-self cells. It is recognised by CD8+ T-cells which are cytotoxic T-cells.

36
Q

MHC class 2

A

Only presents on the membranes of Antigen presenting cells (APC’s). Allows for immune cell communication. It is recognised by CD4+ T cells which are T helper cells. It helps activate and recruit leukocytes (mainly T then B lymphocytes) to launch an appropriate adaptive immune response

37
Q

Antigen presenting cells

A

Dendritic cells, Macrophages, B cells and Monocytes

38
Q

What is more important MHC class 1 or MHC class 2

A

In allograft transplantation the transplant tissue is perceived as foreign due to the presence of non-host MHC class 1 complexes, which causes inappropriate T cell activation. MHC Class 2 molecules do play a fundamental role in initiating and propagating immune responses which facilitate allograft transplantation rejection.

39
Q

What gene encodes MHC class 1 and MHC class 2

A

The Human Leukocyte Antigens (HLA) genes

40
Q

Tissue matching

A

Tissue matching pairs individuals with similar HLA genes and hence similar MHC protein complexes. The three MHC I genes (HLA-A, HLA-B, HLA-C) are the most important in determining compatibility. Because HLA genes are highly polymorphic a complete match is never fully possible unless it’s a genetically identical donor (twin). Instead you try and match them as close as possible

41
Q

Allogenic MHC complexes

A

Genetically different MHC complexes that differ between host and donor. In solid organ transplantation (liver, heart) these will be on the surface of the donor tissue and cells.

42
Q

The 2 mechanisms APC’s can initiate allograft transplantation rejection

A
  • Indirect allorecognition rejection= the antigen presenting cell originates from the host’s immune system.
  • Direct allorecognition rejection= the antigen presenting cell originates from the donor graft tissue.
43
Q

AlloAntigens

A

Peptides generated from the degradation of cystolic proteins within the non-host cell

44
Q

Indirect Allorecognition (MHC2)

A
  1. In the transplantation process the donated organ is damaged. The dendritic cell phagocytosis’s the donor tissue.
  2. During Phagocytosis the dendritic cell takes up and presents donor alloantigens on their MHC 2 complexes.
  3. In the lymph node, CD4+ T helper cells recognise and bind donor alloantigen/MHC 2 complexes presented on the hosts APC’s. The T helper cells will produce cytokines to stimulate B cells to differentiate into plasma cells.
  4. Differentiated plasma cells undergo Antigenic switch, switching from making IgM antibodies to IgG (Immunoglobulin G) antibodies specific to the MHC1 complexes on the donated tissue.
  5. Opsonisation- IgG antibodies bind to the donor alloantigen (MHC 1) resulting in antibody mediated injury to the donated tissue via activation and recruitment of leukocytes. There is recruitment of compliment proteins and activation of the compliment cascade.
45
Q

How does the tissue die in indirect Allorecognition

A

1) Endotheliitis which is when the graft undergoes ischaemia as a result of destruction of the endothelial cells and blood supply. Leading to ischaemia and hypoxia in the transplant tissue.
2) Targeted tissue destruction mediated by natural killer cells in a process known as antibody dependent cellular toxicity, or via neutrophils as they release ROS (reactive oxygen species).
3) The Helper T cell can release Cytokines like IFN gamma which activate Macrophages to increase Endotheliitis and targeted tissue destruction.

46
Q

MHC1 class transplant rejection

A

MHC class 1 complexes bind to ‘AlloAntigens’, peptides generated from the degradation of cystolic proteins within non-host cells. The TCR receptors on the cytotoxic T cells recognises the proteins that make up the allogenic MHC class 1 complexes as being foreign. The CD8+ Cytotoxic T cell launches and immune response and degranulates. Apoptosis is mediated by cytotoxins (perforin, granzymes).

47
Q

Direct Allorecognition (MHC1 and MHC2)- identifying foreign material

A
  • The Donor tissue becomes damaged, and is phagocytosed by dendritic cells (originating from the donor). The dendritic cell takes up the alloantigens onto its MHC2 complex.
  • Donor APC express their own allogenic MHC class 1 and allogenic MHC class 2 complexes on their surface.
  • The hosts T helper cells recognise and bind to donor MHC class 2 complexes presented on Donor APC’s. The T helper cells generate cytokines and cooperatively active cytotoxic T cells.
  • The hosts Cytotoxic T cells recognise and bind to donor Allogenic MHC class 1 complexes which are presented on the donors APC’s.
48
Q

Direct Allorecognition (MHC1 and MHC2)- Reacting to foreign material

A
  • Cytotoxic T cells are now activated to recognise and destroy donor graft tissue which express allogenic MHC class 1 complexes. It will bind and degranulate causing Apoptosis mediated by cytotoxins (perforins, granzymes). This causes targeted tissue destruction and Endothaliitis
  • The T helper cells are bound to the MHC class 2 molecules, which are presented on the donor APC’s. They stimulate and activate B cells to ultimately produce IgG antibodies. The antibodies are specific to donor allogenic MHC class 1 complexes which lead to antibody mediated injury to graft tissue.
49
Q

Tissue rejection- bone marrow transplant

A

There is potential for transplanted T cells (Cytotoxic T cells and Helper T cells) to perceive the entire recipients body as foreign as the immune cells originate from the bone marrow. This is termed graft versus host defence. To avoid this bone marrow transplants require very accurate tissue matching using HLA gene matching.

50
Q

How do you prevent transplantation rejection

A

Pharmacological immunosuppression is used. The patient receives continual drug therapy and immunosuppression for the life of their graft.

51
Q

What cytokines do most immunosuppressants block

A

The majority of immunosuppressants block the function and or production of Interleukin 2 (IL-2). IL-2 is an important cytokine required for the activation and growth of T cells. This will suppress T cell activation and growth:

52
Q

Glucocorticoids

A

Prednisolone. Prevents activation of APC’s and transcription of the IL-2 gene. Glucocorticoid receptor complexes directly bind to the p65 subunit of the NF-kB and this prevents NF-kB activation of inflammatory genes including IL-2. Thus preventing gene transcription. The Glucocorticoid receptor also binds to DNA promoting IkBa synthesis which prevents p50/p65 nuclear translocation to the nucleus. This prevents NF-kB activation of inflammatory genes including IL-2.

53
Q

Calcineurin inhibitors

A

Tacrolimus (TAC) or cyclosporine (CsA). Normally the activated TCR leads to an increase in Ca+2 levels, this binds and activates Calmodulin. Calmodulin binds to Calcineurin (Phosphatase). This removes a phosphate group from the transcription factor NF-AT. This then binds to the IL-2 gene producing IL-2. Calcineurin inhibitors blocks the Calcineurin’s activity. Cyclosporine binds to Cyclophilins, TAC binds to a protein called FKBP. They both block Calcineurin’s activity.

54
Q

Activity of Tacrolimus (TAC) and Cyclosporine (CsA)

A

Cyclosporine binds to Cyclophilins, TAC binds to a protein called FKBP. They both block Calcineurin’s activity.

55
Q

Il-2 receptor antagonists

A

Daclizumab / Basiliximab.

1) Daclizumab is a humanised monoclonal antibody which binds to the alpha subunit of the IL-2 receptors (CD25) of T cells, preventing this function.
2) Basiliximab is a chimeric mouse, a human monoclonal antibody to the alpha subunit of the IL-2 receptor (CD25) of T cells. The antibodies prevent IL-2 binding to the receptor preventing IL-2 mediated T cell activation.

56
Q

T cell receptor antagonists

A

OKT3 (muromonab) is a murine monoclonal antibody which binds to the CH3 complex preventing its function. It acts in two phases:

  1. OKT3 causes increased T cell depletion from liver circulation.
  2. OKT3 promotes the removal of an important activator domain on the T cell receptor of Cytotoxic T cells and Helper T cells. This produces immune-incompetent T cells.
57
Q

Immunosuppressants- Therapeutic drug monitoring

A

All immunosuppressive agents present toxic side effects. So, a narrow therapeutic window needs to be achieved for optimal clinical outcome. However, pharmacodynamics vary significantly between individual patients making predictive dosing extremely difficult. Therapeutic drug monitoring (TDM) is essential for post-transplantation patient care.

58
Q

Side effects of Immunosuppressive medication

A
  • Toxicity
  • Cancer
  • Infection
  • Cushing’s disease
  • Quality of life
  • Excess hair growth/loss
  • Tremor
  • Dental problems
59
Q

Gallstones

A

Gallstones are made from components of bile. They are classified whether they are primarily made of cholesterol or pigment. They may go unnoticed and produce no symptoms or get stuck along the biliary tree. The symptoms depend on where in the biliary tree they are lodged.

60
Q

Cholelithiasis

A

The presence of stones in the gallbladder

61
Q

Cholesterol stones

A

(80% cholesterol by weight)- they vary in colour from light yellow to dark-green or brown. They are oval. They often have a tiny dark central spot. Account for 60-80% of gallstones. They occur as solitary stones, in pairs or as multiple mulberry stones. It is associated with high cholesterol, pregnancy, diabetes and the oral contraceptive pill.

62
Q

How cholesterol stones form

A
  1. The bile is super-saturated with cholesterol and so the cholesterol can no longer be held in solution.
  2. Decreased amount of bile acids and salts, cannot keep the cholesterol in the solution.
  3. Gall bladder hypomotility- cholesterol separates and precipitates out.
63
Q

Pigment stones

A

Small dark stones made of bilirubin, calcium salts and 20% cholesterol that are found in the bile. They are irregular, gritty and fragile. You tend to get multiple of them/ They are associated with increased haemolysis. Results in increased circulating unconjugated bilirubin. The increased concentrations of unconjugated bilirubin in the bile forms complexes with calcium. Calcium bilrubinate precipitates.

64
Q

Mixed gallstones

A

Typically contain 20-80% cholesterol. Often contain calcium, phosphate, bilirubin and other bile pigments. Because of the bile contents they are radiographically visible. They are brown. Tend to arise secondary to infection or after biliary surgery. Damaged hepatocytes and bacteria release beta glucuronidase which hydrolyses conjugated bilirubin. Stones form as the now unconjugated bilirubin is insoluble.

Medicine year 1 semester 2 (61 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions