Respi + GI PYQ Flashcards
(36 cards)
Alpha1 antitrypsin deficiency chromosome
The al-antitrypsin is encoded by the proteinase inhibitor (Pi) locus on chromosome 14.
al-AT is a polymorphic gene located on chromosome 14. It is part of a larger family of structurally unique serine protease inhibitors, referred to as serpins. The most common clinically significant mutation in a1-antitrypsin deficiency is Pizz.
al-antitrypsin, normally present in serum, tissue fluids, and macrophages is a major inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation. The absence of a1- antitrypsin activity results in excessive digestion of elastic tissue by elastase.
Patients with a1-antitrypsin deficiency have a markedly increased tendency to develop panacinar emphysema.
M/c lung finding in COVID 19
Diffuse alveolar damage may be seen in patients suffering from COVID-19.
COVID-19 related histopathological changes in the lungs include:
1. Diffuse alveolar damage
2. Hyaline membrane formation
3. Desquamation of pneumocytes
4. Fibrin deposits in lungs
5. Inflammation with mononuclear cells
Whipple’s disease
Cause of malabsorption in
In Whipple’s disease, the cause of malabsorption is impaired lymphatic transport.
In Whipple disease, clinical symptoms occur because organism-laden macrophages accumulate within the small intestinal lamina
propria and mesenteric lymph nodes, causing lymphatic obstruction. These bacteria-laden macrophages also accumulate within mesenteric lymph nodes, synovial membranes of affected joints, cardiac valves, brain.
Triad
The clinical presentation of Whipple disease is usually a triad of diarrhea, weight loss, and arthralgia.
Colorectal polyps
Neoplastic
Adenomatous polyps:
• Tubular adenoma (Most common)
• Tubulovillous adenomas
• Villous adenoma (highest risk of malignancy)
Non-neoplastic:
• Hyperplastic
• Hamartomatous
• Juvenile polyp (solitary)-benign
• Juvenile polyposis syndromes (multiple)-premalignant
• Peutz-Jeghers syndrome- occasionally carcinoma may develop.
• Cronkite-Canada syndrome*
• Inflammatory
• Pseudopolyp
• Benign lymphoid polyp
Note:
*Cronkite-Canada syndrome: Cancer occurs in the stomach, colon, and rectum, but it remains controversial whether these polyps possess malignant potential. As many as 15% of patients with Cronkite- Canada syndrome have a malignant
Cronkhite-Canada syndrome.
intestinal polyps, cutaneous pigmentation, and diarrhea points toward a diagnosis of Cronkhite-Canada syndrome.
It is a non-hereditary polyposis syndrome that occurs at a mean age of 50 years.
Clinical features include:
• Diarrhea and abdominal pain
• Nail atrophy, hair loss, and cutaneous hyperpigmentation
• Cachexia and anemia
• Characterized by hamartomatous polyps of the stomach, small intestine, and colon due to abnormalities in the nopolypoid mucosa
Wilson’s disease testing asymptomatic
Genetic testing for the ATP7B gene
is used to screen asymptomatic 1st and 2nd-degree relatives of patients with Wilson’s disease. This helps to differentiate the heterozygous from the homozygous individuals. This can be useful in the early initiation of treatment before the onset of symptoms.
Low serum ceruloplasmin, raised 24 hr urinary copper and Kayser-Fleischer rings are diagnostically helpful.
Estimation of hepatic tissue copper is the gold standard for diagnosis. It is measured using neutron activation analysis / atomic absorption spectrometry.
Ménétrier disease.
Menetrier disease is one of the causes of hypertrophic gastropathy. It is associated with diffuse hyperplasia of the foveolar epithelium and hypoproteinemia due to protein-losing enteropathy. There is an increased risk of gastric adenocarcinoma in adults.
histological image shows hyperplasia of foveolar mucous cells. The glands are cystically dilated and elongated with a corkscrew-like appearance.
irregular enlargement of the gastric rugae in the body is suggestive of Ménétrier disease. It is due to excessive secretion of transforming growth factor a (TGF-a).
Celiac disease or gluten sensitive enteripathy
It is associated with HLA-DQ2 and HLA-DQ8 alleles.
immune-mediated enteropathy triggered by the ingestion of gluten-containing foods such as barley, rye, oats, and wheat (mnemonic:
BROW
digestion of the gluten-containing diet leads to the formation of gliadin peptides. These peptides result in the following immune reactions:
activate the epithelial cells to express certain cytokines (IL-15), which result in CD8+ T cell proliferation
undergo deamidation and interact with
HLA-DQ2 or HLA-DQ8 on the antigen-presenting cells. This leads to CD4+ T cell stimulation and further cytokine production
Antibodies a/w celiac ds
Anti gliadin ab
Anti ttg ab
Anti endomysial ab
Microscopic findings include:
• Villi atrophy and flattening
• Crypt hyperplasia
• Increased intraepithelial T cells
Autoimmune Gut and Skin Diseases and HLA
associations
Gluten-sensitive enteropathy (celiac disease)-DQ2, DQ8
Chronic active hepatitis-DR3
Dermatitis herpetiformis-DR3
SLE(white)-DR3
Sjogren’s syndrome-DR3
Psoriasis vulgaris-Cw6
Pemphigus vulgaris-DRA, DQ1
Bullous pemphigoid variant-DQ7
Autoimmune Endocrine
Diseases and HLA
associations
Type 1 diabetes mellitus
DQ8, DR4, DR3,
DR2
Hyperthyroidism (Graves’)
B8, DR3
Hyperthyroidism (Japanese)
B35
Adrenal insufficiency
DR3
Important
Diseases and their
HLA Associations
Mutation in Wilson’s ds
Wilson’s disease is caused due to a loss-of-function mutation in the ATP7B gene. It an autosomal recessive condition.
The ATP7B gene is located on chromosome 13q. The gene encodes a copper transporting ATPase (ATP7B) which has 2 functions:
• Maintains copper in bound form by binding copper to apoceruloplasmin
• Helps excrete free copper in bile.
Menke’s ds
Menkes disease is an X-linked recessive condition leading to impaired absorption of copper and subsequent copper deficiency.
Here, the mutation is in the ATP7A gene.
A chronic alcoholic developed cirrhosis of the liver. Which is the principal cell type involved in scar deposition in this condition?
The principal cell type involved in scar deposition in cirrhosis of the liver is the hepatic stellate cells or Ito cells.
Hepatic stellate cells deposit primarily type I and type Ill collagen in the lobule and cause fibrosis. In their quiescent form, these cells store lipids and vitamin A.
ARDS in Covid 19
Damage to the endothelial (Labelled as A) cells, with inflammation, is the key initiating event and the basis of lung damage. Neutrophils play a significant role in tissue injury in this condition.
Shock lung also known as ARDS/HMD/ALI (acute lung injury) is characterized histologically by diffuse alveolar damage (DAD). The characteristic histological picture is that of a hyaline membrane lining the alveolar walls.
Edema, scattered neutrophils and macrophages, and necrotic epithelial cells are also present.
Histologic findings in COVID-19 patients :
• Diffuse alveolar damage
• Inflammation with mononuclear cells
The given HP slide shows diffuse alveolar damage which is the most common finding in the histopathological analysis of COVID-19
infected lungs with ARDS.
Pulmonary hamartoma
Pulmonary hamartoma consists of nodules of connective tissue intersected by epithelial clefts.
There are islands of cartilage, fat, smooth muscle, and entrapped respiratory epithelium in pulmonary hamartoma.
It is a benign clonal neoplasm associated with chromosomal aberrations involving either 6p21 or 12q14-q15.
Lung hamartoma is usually discovered as an incidental coin lesion on a routine chest
radiograph.
Esophagitis in healthy individuals caused by
HSV herpes simplex virus
In immunocompromised individuals caused by -
HSV
CMV
CANDIDA
ARDS causes
Sepsis
Diffuse pulmonary infections
Infections- mycoplasma pneumocystis jirovecii. miliary TB GASTRIC ASPIRATION MECHANICAL TRAUMA BURNS NEAR DROWNING
Characterstick finding of ARDS
Diffuse alveolar damage
Heart failure is not a/w diffuse alveolar damage
Adenocarcinoma of lung
Cough hemoptysis weight loss and TTF-1(thyroid transcription factor-1) positivity along with microscopy showing glands taking up ttf-1 stain turning brown
M/c type of carcinoma seen in women and non smokers
Usually seen in peripheries
Precursor lesion of adenocarcinoma - atypical adenomatous hyperplasia
Mol genetics - freq mutations in EGFR ALK ROS MET RET KRAS mutations
Microscopic exam- Lepidic pattern of growth at the periphery of tumor
SCC squamous cell Ca of lung
p40 and p63 are markers of SCC lung
MC CANCER in SMOKERS
Histo
Charact. By keratinisation and markedly eosinophilia cytoplasm
