PAT 90- Flashcards
1
Q
patterns of liver cell injury
A
- degenerative
- apoptosis
- necrosis of hepatocytes
- Regeneration of lost hepatocytes
- Scar Formation and Regression
2
Q
how is the degeneration of liver cell injury
A
potentially reversible changes, such as
1. hydropic degeneration
2. accumulation of fat (steatosis)
3. bilirubin (cholestasis)
3
Q
name of acidophilic apoptotic bodies in yellow fever
A
Councilman bodies
4
Q
how the apoptosis occur in liver cells
A
- The hepatocytes undergo shrinkage,
- nuclear chromatin condensation (pyknosis),
- fragmentation (karyorrhexis),
- and cellular fragmentation into acidophilic apoptotic bodies
5
Q
The principal cell type involved in scar
deposition in liver
A
hepatic stellate cell
6
Q
A
6
Q
what is the hepatic stellate cell in its quiescent form and in acute and chronic injury
A
In its quiescent form, it is a lipid (vitamin A) storing cell. However, in several forms of acute and chronic injury, the stellate cells can become activated and are converted into highly fibrogenic myofibroblast
7
Q
viruses cause viral hepatitis
A
Epstein Barr virus [EBV], cytomegalovirus, and yellow fever virus
ABCDE hepatotropic viruses
8
Q
hepatic viruses transmitted fecco oral
A
HAV
HEV
9
Q
trasmission of HBV and HCV
A
a. By blood, blood components and contaminated instruments e.g. in intravenous (IV) drug abuse.
b. Sexual transmission
d. Transplacental transmission.
10
Q
transmission of HDV
A
HDV infection can develop only when there is concomitant HBV infection
11
Q
the most common cause of chronic hepatitis in Egypt
A
HCV
12
Q
viral infection of increased hepatocellular carcinoma
A
HBV
13
Q
causes fatal fulminant hepatitis in pregnant
women
A
HEV
14
Q
hepatic viral infection do not cause chronic disease
A
HAV and HEV
14
Q
hepatic viral infections are frequently sub-clinical
A
HAV and HBV
15
Q
Acute asymptomatic infection with recovery in viral heaptitis based on
A
elevated transaminases, or by anti-viral antibody titers
16
Q
Acute asymptomatic hepatic viral infection with recovery caused by
A
HAV and HBV
17
Q
Acute symptomatic hepatic viral infection with recovery
A
HEV, HBV or HCV
18
Q
The carrier state the of viral hepatitis caused by
A
HBV or HCV
18
Q
Gross of acute viral hepatitis
A
Liver is enlarged and greenish yellow
19
Q
Microscopic picture of acute viral hepatitis
A
- Liver cell injury :
* Hydropic degeneration (ballooning) of hepatocytes.
* Apoptosis of individual cells, resulting in acidophil bodies, usual with adjacent T cells (lobular hepatitis).
* Focal necrosis (drop out), leaving collapsed reticulin network behind.
Scavenger macrophages mark the sites of dopout.
* In severe cases, confluent necrosis occurs, commonly centrilobular, or even central-portal bridging necrosis. - Cholestasis:
Accumulation of bile in the liver cells and bile canaliculi (obstructed by swollen hepatocytes)
Kupffer cells engulf bile and undergo hyperplasia. - Portal tract inflammation: In the form of mild mononuclear cell infiltration.
20
Q
Clinical picture of acute viral hepatitis
A
Nausea, vomiting, abdominal pain followed by jaundice.
21
Q
gross of Acute Massive Necrosis
A
Shrunken liver, mottled yellow (necrosis) and red (hemorrhage) areas, with wrinkled capsule
22
microscopic picture of Acute Massive Necrosis
Massive diffuse liver cell necrosis, sinusoidal rupture,
inflammatory cells (lymphocytes, macrophages, plasma cells)
23
patient develop post necrotic cirrhosis
patient that have survived from Sub massive Necrosis
24
def of chronic hepatitis
Chronic hepatitis is defined by the presence of symptomatic, biochemical, or serologic evidence of continuing or relapsing hepatic disease for more than 6 months, with histologically documented inflammation and necrosis
25
Etiology of chronic hepatitis
* Viral etiology (most common): HBV (+ HDV) or HCV. Mixed infection may occur.
* Autoimmune: Caused by autoantibodies as antinuclear antibodies & anti-actin antibodies.
* Drug induced: Isoniazid, methyl dopa
* Metabolic diseases as :
(a) α 1 antitrypsin deficiency
(b) hemochromatosis
(c) Wilson's diseases.
* Cryptogenic (undetermined etiology).
26
27
Gross of chronic viral hepatitis
mild hepatomegaly
28
Def of chronic viral hepatitis
A **chronic necro-inflammator**y disease caused by** HCV or HBV**.
The pathological changes characteristically start at 'the interface', which is the **parenchymo- mesenchymal interface **between hepatic lobules and portal tracts
29
microscopic picture of chronic viral hepatitis
1) Inflammation: (in variable degrees)
* Portal inflammation: Expansion of the portal tracts by chronic inflammatory cells; mainly lymphocytes. Bile duct walls may be inflamed (mainly in HCV infection).
* Lobular inflammation (lobular hepatitis): Usually mild.
2) Necrosis: It may be:
* Piecemeal necrosis (interface hepatitis): This is inflammation with destruction of the liver cells at the limiting plates of liver lobules (i.e. the parenchymomesenchymal interface). The liver cells become detached.
* Spotty ( focal )
Confluent, bridging, or multiacinar necrosis occurs in severe cases.
* Apoptosis may also occur
3) Fibrosis: It may be:
Portal fibrosis, bridging fibrosis, or bridging fibrosis accompanied by regeneration nodules (cirrhosis)
30
Steatosis of hepatocytes related to
HCV
31
Ground glass hepatocytes related to
HBV
32
Complications of chronic viral hepatitis
1. Post hepatitic cirrhosis.
2. Liver failure.
3. Hepatocellular carcinoma
33
Grading of Chronic Hepatitis based on
extent of interface hepatitis,
the degree of bridging necrosis,
the frequency of hepatocyte apoptosis
the density of portal inflammation
33
The most popular grading & staging systems are
* Ishak scores the grade out of 18, and the stage out of 6. 6/6 is cirrhosis.
* Metavir scores the grade from A0 to A4 and the stage from FO to F4. F4 is cirrhosis
34
solitary liver abscess
¨ Amoebic abscess.
¨ Infected hydatid cyst.
¨ Complicating cholecystitis.
¨ Traumatic (penetrating Injury)
35
Multiple liver abcesses
¨ Amoebic abscess.
¨ Abscesses of ascending cholangitis.
¨ Actinomycosis.
¨ Pyemic abscesses.
36
Etiology of amoebic liver abscess
Amoeba trophozoites enter portal venous radicals in colonic submucosa to reach liver
37
Gross of Amoebic Liver Abscess
§ Single, but may be multiple, large being mostly in right lobe.
§ Wall is necrotic & the lining is shreddy.
§ Its contents is a brown liquid material (chocolate pus).
38
microscopic picuture of Amoebic Liver Abscess
- Amoeba in the liver causes necrosis, which becomes secondarily infected & purulent (the grossly yellow pus quickly turns brown due to excessive hemorrhage).
- The wall of the abscess is composed of necrotic liver tissue with frequent vegetative forms of amoeba surrounded by a clear halo due to lytic enzymes secreted from the amoeba.
- The inflammatory reaction consists of lymphocytes, plasma cells & macrophages.
39
etiology of Ascending Cholangitic Abscesses
Caused by mixed flora: E coli, staphylococcus aureus & anaerobic bacilli
40
pathological features of Ascending Cholangitic Abscesses
- Multiple, yellow, small, abscesses,
- mostly in portal tract areas around the bile ducts.
- The bile ducts show all features of an acute suppurative Inflammation &
- their lumen contains pus
40
liver abscess lined by irregular yellow membrane
Pyemic Abscesses
41
GRANULOMATOUS DISEASE of liver
tuberculosis, sarcoidosis, bilharziasis and primary biliary cirrhosis
42
Def of liver cirrhosis
* Progressive necrosis of liver cells with destruction of liver architecture (framework).
* Repair in liver cells by regeneration (regeneration nodules) and in framework by fibrosis.
43
Etiology and Types of liver cirrhosis
1- Post-Hepatitic Cirrhosis: Chronic viral hepatitis B and C
2- Post-Necrotic Cirrhosis
3- Nutritional and Alcoholic Cirrhosis (Laennec's Cirrhosis)
4- Primary biliary cirrhosis ( intrahepatic biliary obstruction )
5- Secondary Biliary Cirrhosis
6- Cirrhosis caused by congenital metabolic disorders
7- Cirrhosis due to chronic venous congestion of the liver (cardiac cirrhosis)
8- obstruction of hepatic veins due to veno-occlusive disease and budd-chiari
44
other name of Nutritional and Alcoholic Cirrhosis
Laennec's Cirrhosis
45
causes of Post-Necrotic Cirrhosis
due to viral hepatitis or toxic hepatitis caused by drugs as isoniazid or chemicals as **carbon tetrachloride**
46
carbon tetrachloride causes.......
Post-Necrotic Cirrhosis
46
causes of Secondary Biliary Cirrhosis
A Congenital biliary atresia.
S Gall stones.
C Compression by large lymph nodes
47
congenital metabolic disorders causes cirrhosis
* Pigment cirrhosis: due to hemochromatosis (bronzed diabetes).
* Wilson's disease. Inherited disease, failure of liver to excrete copper in bile and copper accumulates in liver and brain).
* Alpha 1 antitrypsin deficiency.
* Glycogen storage disease.
48
main complications of cirrhosis
1) Liver cell failure.
2) Portal hypertension.
3) Hepatocellular carcinoma.
48
Gross of liver cirrhosis
1. The liver is decreased in size and weight due to loss of liver tissue & fibrous tissue shrinkage.
2. The surface and cut section are nodular. According to size of regeneration nodules , cirrhosis is classified into :
* Micronodular cirrhosis: 1-3 mm in diameter. .
* Macronodular cirrhosis: >3 mm in diameter.
* Mixed micro and macro nodular cirrhosis.
3. The color is :
* Yellow in cases of nutritional or alcoholic cirrhosis (fatty change).
* Green in case of biliary cirrhosis
* Dark brown in case of hemochromatosis.
4. Consistency is firmer than normal, edges are sharp & retracted cut section (due to fibrosis)
49
causes mixed nodular cirrhosis
post hepatitic cirrhosis
50
causes macro nodular cirrhosis
post necrotic
wilson
51
the color of the liver is yellow in which type of cirrhosis
nutritional or alcoholic cirrhosis and post hepatitic
52
the color of the liver is green in which type of cirrhosis
biliary cirrhosis
53
the color of the liver is dark brown in which type of cirrhosis
hemochromatosis.
54
microscopic picture of cirrhosis
1) Regeneration nodules:
- Regenerating hepatocytes are arranged in collections trying to simulate a liver lobule but the sinusoids are irregular and the central vein may be absent, and these masses of regenerating hepatocytes are totally surrounded by fibrous bands
- - Liver cells proliferate haphazardly so that the liver cell plates, which are normally one cell thick, are two cell thick and not radiating from the central vein.
- Regenerating liver cells may be binucleated & may also undergo dysplastic changes (predisposes to carcinoma).
- Other changes that may be observed according to the cause: necrotic foci, fatty change, hydropic changes, Mallory bodies or ground glass appearance of virus B infection.
2) Fibrosis:
- in the form of bands of collagen encircling the regenerating nodules & involving the portal areas.
- According to the presence or absence of inflammatory cells within the fibrous septae, cirrhosis is either active (i.e. contain lymphocytes, plasma cells & macrophages) or inactive.
3) The portal tracts are widened by the fibrosis, the inflammatory cells & show proliferating bile ducts & angiomatoids (opening of anastomosis between arteries and portal vein). In case with active. cirrhosis apart from inflammation , piecemeal necrosis ( interface hepatitis ) at the limiting plate may also be seen
55
etiology of Primary Biliary Cirrhosis
* This is an autoimmune disease.
* In 95 % of cases serum anti-mitochondrial antibodies are detected.
* The disease mostly affects middle-aged females.
55
Gross of primary biliary cirrhosis
Liver is enlarged, green (bile-stained) with micronodular cut surface
56
microscopic picture of primary biliary cirrhosis
4 stages:
1) Lymphocytes and plasma cells surround and infiltrate the medium. sized ducts, and granulomas may develop around the ducts . Finally most of the ducts disappear (ductopenia).
2) As result of ductopenia, proliferation of the small ductules occurs.
3) Stage of scarring: progressive fibrosis.
4) Stage of established cirrhosis: Cirrhosis is due to progressive liver injury caused by bile retention (cholestasis) due to ductopenia. Regeneration nodules are usually micronodular.
57
There are three (overlapping) forms of alcoholic related liver disease
§ Hepatic steatosis (fatty liver).
§ Alcoholic steato-hepatitis.
§ Alcoholic cirrhosis.
57
Etiology of alcoholic liver disease
- Alcohol is metabolized in the hepatocytes producing toxic acetaldehyde.
- This along with the malnutrition associated with chronic drinking results in acute liver disease
57
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD) is associated to
insulin resistance, diabetes mellitus, hypertension and dyslipidemia
57
mechanism of alcoholic liver disease
Toxicity of alcohol leads to decreased fatty acid oxidation, increased synthesis of triglycerides & impaired secretion of lipoproteins by liver cell.
The associated malnutrition causes increased fat mobilization from stores & decreased lipotropic factors which results in steatosis.
58
Liver failure is characterized clinically by
a. Hypoalbuminemia
b. Easy bruising due to clotting factor deficiency.
c. Jaundice
d. Ascitis:
e. Hyperestrenism
f. Encephalopathy
h. Hepatorenal syndrome
58
cause of ascites caused by renal failure
hypoalbuminemia, portal hypertension and salt and water retention
59
Hyperestrenism manifestions
* spider nevi and telangiectasia
* Loss of chest hair, change in distribution of pubic hair, testicular atrophy & gynecomastia (breast enlargement)
59
Cause of portal hypertension in liver cirrhosis
* Obstruction of portal blood flow by fibrosis and regeneration nodule
* Transmission of arterial pressure to portal circulation via anastomosis between the arterial and portal veins in the fibrous septae of the liver.
* Splanchnic arterial vasodilatation leading to increase in portal venous flow Effect of portal hypertension
60
nodularity of cirrhosis causing hepatocellular carcinoma
macronodular
61
breath odor of patient with liver failure
(rotten apple) called fetor hepaticus
62
pre sinosoidal causes of portal hypertension
Portal vein thrombosis
- Tumor
- Infection
Portal tract fibrosis
- Schistosomiasis
- Sarcoidosis
- Biliary cirrhosis
63
sinosoidal causes of portal hypertension
Cirrhosis
64
post sinosoidal causes of portal hypertension
* Veno-occlusive disease ( bush tea, some drugs )
* Budd-Chiari syndrome ( hepatic vein thrombosis )
65
portosystemic shunts leads to
Esophageal varices
Rectum (hemorrhoids)
Falciform ligament and umbilicus (caput medusa)
66
f
67
types of gall bladder stones
① Cholesterol stones:
Associated with hypercholesterolemia , obesity . diabetes and pregnancy .
So it is common in fatty fertile females in their forties.
② Pigment stone ( bilirubin stone ):
§ Pure pigment stone is associated with hemolytic anemia with increased excretion of bilirubin .
③ Mixed stones :
§ Cystic duct obstruction , producing 2ry infection & water absorption from the wall of gall bladder .
Contents become concentrated & the bile salts deposit around shedded epithelial cells & inflammatory exudate forming a mixed type of stone containing all components of the bile (cholesterol , pigment & calcium carbonate)
67
Clinical Consequences Of Portal Hypertension
Ascites
Portosystemic shunts
Splenomegaly
Hepatic encephalopathy
68
what is the combined galls stone
It is a cholesterol stone, which changes its appearance at the start of 2ry infection of the bile i.e. central cholesterol stone with outer mixed stone shell
69
Morphology of cholesterol stone
Cholesterol stone
* is usually single 1-5 cms, yellowish-white, large & has a mamillated surface .
* On section, it has a radiating crystalline center .
* By X - ray it is radioluscent ( can't be seen & needs a dye to be observed )
70
morphology of Pigment stone
* Pigment stones ( bilirubin stones ) : Multiple , small ,
* dark & have a smooth surface .
* On section, they are very dark.
* By X ray, they are radiopaque.
71
morphology of mixed stones
* The stones are multiple , soft-firm , resulting in flattening of some surfaces when in contact with one another i.e. faceted .
* On section they have a laminated cross section with different colored layers.
* By X-ray it is radiopaque.
72
Complications of Gall bladder stones
Predisposes to carcinoma
cholecystitis
Acute pancreatitis
obstruction of the common bile duct causing colic and jaundice
obstruction in the intestine by gall stone passing through fistula
obstruction of cystic duct causing mucocele and hydrops
| 1 carcinoma 2 inflammation 3 obstruction
73
Etiology of acute cholecystitis
obstruction of cystic duct
74
Complications of acute cholecystitis
1) Gangrene
2) Perforation resulting in septic peritonitis
3) Adhesions and fistulous tract between gall bladder and duodenum leading to passage of gall stone to the intestine.
4) Chronic cholecystitis
75
Rokitansky-Aschoff sinuses related to
CHRONIC CHOLECYSTITIS
76
Complications of chronic cholecystitis
1- Repeated acute attacks.
2- Gall stone formation.
77
Definition of Acute Hemorrhagic Pancreatitis
Acute inflammation of the pancreas
77
Most gallbladder carcinomas are
adenocarcinomas
77
microscopic picture of chronic cholecystitis
Rokitansky-Aschoff sinuses
78
diagnostic marker of acute hemorrhagic pancreatitis
marked elevation of serum amylase
79
morphology of acute hemorrhagic pancreatitis
1. Early the gland is swollen , edematous and hyperemic .
2. Proteases digest the wall of blood vessels with extravasation of blood , and the inflammation becomes hemorrhagic. Amylase is released in the blood and is a diagnostic marker of the condition.
3. Lipases cause fat necrosis of peri - pancreatic fat which can be quite extensive within the abdomen .
Fat necrosis appears as chalky white areas due binding of calcium
80
Etiology of acute hemorrhagic pancreatitis
Pancreatic necrosis , hemorrhage and inflammation may be due to :
1- Obstruction of ampulla of Vater by gall stone .
Thus bile passes into pancreatic duct and activates trypsinogen into trypsin which digests the pancreatic tissue .
2- Excess alcohol abuse may lead to increased secretion of pancreatic juice and
contraction of sphincter of oddi leading to rupture of pancreatic duct.
3- Accidental surgical injury of pancreas.
4- Hyperparathyroidism.
5- Polyarteritis nodosa.
6- Viral and bacterial infection
81
Complications acute hemorrhagic pancreatitis
* Death ( 5 % of patients ) can occur from shock , acute respiratory distress syndrome or acute renal failure .
* Pancreatic pseudocysts can result from accumulation of liquefied necrotic material.
81
Complications of chronic Pancreatitis
1- Malabsorption.
2- Diabetes mellitus.
3- Pseudocysts.
82
the most common secondary tumors of peritoneum
ovarian and pancreatic adenocarcinomas are the most common
83
Majority of pancreatic cancers arise in which part of pancreas
head of the gland, followed by the
body then the tail
84
congenital anomalies of kidney
85
86
complete absence of one kidney
86
Failure of the kidney to develop to the normal size
Hypoplasia of kidney
87
* Double or extra renal pelvis,
* Anomalies in renal arteries &
* Double ureters
Miscellaneous
anomalies
88
cause of adult polycystic kidney
failure of fusion of convoluted
and collecting tubules
89
account for 20% of renal failure in
children
Renal dysplasia and renal hypoplasia
90
disease associated with congenital cystic liver & congenital cerebral aneurysms
Adult Polycystic Kidney
91
Both kidneys are fused together
Horse shoe
kidney
91
kidney fails to migrate up to normal position
& remains in the pelvis.
Ectopic
kidney
92
Gross of Adult Polycystic Kidney
* Kidneys:
enlarged & may reach enormous size
may weigh up 4 Kg
* Cysts:
variable sizes
clear or bluish content.
may be communicating together but not with the renal pelvis.
93
microscopic of Adult Polycystic Kidney
* Cysts:
lined by flat or cubical epithelium
* Nephrons:
detected between the cysts.
94
type of congenital anomaly of infantil polycystic kidney
autosomal recessive
anomaly
94
is the most common cause of chronic renal
)ملحوظه هامه( failure
Chronic glomerulonephritis
95
is the most common type of glomerular injury as glomerular deposits of immunuglobulins
Antibody mediated injury
95
Two forms of antibody mediated injury of glomerular
➢ The antibodies react directly with intrinsic tissue antigens (Anti GBM nephritis) or planted antigens (IgA nephropathy).
➢ Deposition of circulating antigen antibody complexes in the glomeruli
96
clinical picture of adult poly cystic kidney
Hematuria
Hypertension
Secondary infections
Chronic Renal Failure (CRF)
97
clinical picture of nephritic syndrome
➢ hematuria
➢ hypertension (mild/ moderate )
➢ proteinuria
➢ edema
➢ oliguria
98
nephritic syndrome is presenting feature of
acute post
streptococcal glomerulonephritis
99
clinical picture of nephrotic syndrome
proteinuria( more than 3.5 gm/day) :-
➢ hypoalbuminemia
➢ severe edema
➢ hyperlipidemia
➢ lipiduria (lipid in urine)
100
Acute Diffuse Proliferative GN is caused by
group A beta hemolytic streptococci
101
location of deposition of ADPGN
subepithelial humps
102
Etiology of Rapidly Progressive G.N
) Post infectious:
▪ follow acute diffuse proliferative GN, especially in adults
2) systemic disease:
▪ as poly arteritis nodosa (PAN) SLE &Good pasture syndrome.
3) Idiopathic.
103
microscopic of ADPGN
* Glomeruli
Enlarged and hypercellular due to proliferation of endothelial mesangial and epithelial cells
* the tubules
show hydropic degeneration and may contain red Cell and granular casts.
* The interstitium
is edematous and may be infiltrated by neutrophils
104
Course of Acute diffuse
1) Complete recovery in
▪ 95% of children and
▪ 65% of adult.
2) Severe hypertension leading to:
▪ acute heart failure (AHF) or
▪ acute renal failure (ARF).
3) Progress to
▪ rapidly progressive GN or
▪ chronic GN
104
Gross of rapidly progressive GN
kidneys are pale, enlarged with petechial hemorrhages on the outer surface
105
Micro of rapidly progressive GN
➢ Glomeruli :-
enlarged,
hypercellular showing proliferation of endothelial , mesangial,
epithelial cell & leucocytic infiltration.
glomerular necrosis and may be glomerular capillary thrombosis.
➢ Crescents :-
formed in the Bowman space and compressing the tufts.
They are formed of proliferating parietal epithelial cells, fibrin and
migrating monocytes and leucocytes
➢ By immunofluorescence microscopy(I/F) :-
in Goodpasture syndrome there is linear deposition
of IgG andC3 along GBM.
106
Course of rapidly progressive GN
Acute renal failure.
Hypertension.
Pulmonary hemorrhage in Goodpasture syndrome
107
It is one of the most common cause of nephrotic syndrome in adult
Membranous Nephropathy
108
infections causes Membranous Nephropathy
Hepatitis B & C and Bilharziasis
109
Etiology of membreanous GN
A) Idiopathic 85% of patient.
B) It may occur in association with:
✓ systemic disease as carcinoma SLE,
✓ infections (Hepatitis B & C and Bilharziasis )
✓ metabolic disorders.
✓ Drugs
110
GN that deposit IgG and C3
ADPGN
RPGN
MGN
MPGN 1 and 3
111
It is the most common cause of NS in children (2-6 years)
Minimal Change Disease
112
diseases considered Nephrotic
minimal change
membranous GN
113
diseases considered nephritic
ADPGN
RPGN
114
diseases considered mixed
MPGN
focal segmented
focal proliferative
IgA nephropathy
115
types of MPGN
type 1: Sub endothelial and mesangial deposits of IgG and C3
type 2: rregular electron dense deposits of C3 in the GBM and mesangium
type 3: Sub epitheial ,mesangial and some subendothelial deposits of IgG and C3
116
definition of Focal Segmental Glomerulosclerosis
It is characterized by sclerosis of only portion of the capillary tuft (segmental) in some glomeruli(focal)
117
Secondary causes of FSGS
heroin abuse or AIDs.
118
location of sclerosis and hyalinosis in FSGS
Juxtamedullary ones
119
IgA deposition
IgA nephropathy
FPGN
120
IgM and c3
FSGS
121
C3 only
MPGN 2
121
IGM and C3
FSGS
FPGN
122
etiology of FPGN secondary to
➢ Upper respiratory tract infections
➢ PAN
➢ SLE
➢ Henoch-Shoenlein purpura
